262 results on '"Sertoli cell proliferation"'
Search Results
2. Regulation of mammalian spermatogenesis by miRNAs
- Author
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William H. Walker
- Subjects
Male ,0301 basic medicine ,endocrine system ,Sertoli cell proliferation ,Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Meiosis ,Downregulation and upregulation ,microRNA ,medicine ,Animals ,Humans ,Spermatogenesis ,urogenital system ,Cell Biology ,Sertoli cell ,Cell biology ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein ,Stem cell ,030217 neurology & neurosurgery ,Developmental Biology ,Dicer - Abstract
Male fertility requires the continual production of sperm by the process of spermatogenesis. This process requires the correct timing of regulatory signals to germ cells during each phase of their development. MicroRNAs (miRNAs) in germ cells and supporting Sertoli cells respond to regulatory signals and cause down- or upregulation of mRNAs and proteins required to produce proteins that act in various pathways to support spermatogenesis. The targets and functional consequences of altered miRNA expression in undifferentiated and differentiating spermatogonia, spermatocytes, spermatids and Sertoli cells are discussed. Mechanisms are reviewed by which miRNAs contribute to decisions that promote spermatogonia stem cell self-renewal versus differentiation, entry into and progression through meiosis, differentiation of spermatids, as well as the regulation of Sertoli cell proliferation and differentiation. Also discussed are miRNA actions providing the very first signals for the differentiation of spermatogonia stem cells in a non-human primate model of puberty initiation.
- Published
- 2022
3. Estradiol ameliorates metformin-inhibited Sertoli cell proliferation via AMPK/TSC2/mTOR signaling pathway
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Yu Sha Wang, Ya Qi Li, Jiao Jiao Zhang, Xian Zhong Wang, and Liang Chen
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Male ,Sertoli cell proliferation ,AMP-Activated Protein Kinases ,Pharmacology ,Food Animals ,Tuberous Sclerosis Complex 2 Protein ,medicine ,Animals ,Small Animals ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Sertoli Cells ,Estradiol ,Equine ,Cell growth ,Chemistry ,TOR Serine-Threonine Kinases ,AMPK ,Sertoli cell ,Metformin ,Respiratory enzyme ,medicine.anatomical_structure ,Animal Science and Zoology ,Signal transduction ,Chickens ,Signal Transduction ,medicine.drug - Abstract
Metformin is a commonly used for treating type 2 diabetes and it acts on a variety of organs including the male reproductive system. 17β-estradiol plays an important role in Sertoli cell (SC) proliferation which determines the germ cell development and spermatogenesis. The aim of this study is to investigate the effect of metformin on immature chicken SC proliferation and the potential mechanisms by which 17β-estradiol regulate this process. Results showed that metformin significantly inhibited SC proliferation, whereas 17β-estradiol weakened the inhibitory effects of metformin on SC viability, cell growth, and cell cycle progression. SC proliferation-inhibiting effect of metformin exposure was regulated by decreasing adenosine triphosphate level and respiratory enzyme activity in the mitochondria; this process was possibly mediated by the adenosine monophosphate-activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin (mTOR) signaling pathway, which was regulated by the down-expressed miR-1764 and by the decreased antioxidant enzyme activity and excessive reactive oxygen species generation. In addition, SCs transfected with the miR-1764 agomir led to an improvement of proliferation capacity through down-regulating AMPKα2 level, which further decreased TSC2 expression and induced mTOR activation. However, the anti-proliferative effect of miR-1764 antagomir can be alleviated by 17β-estradiol treatment via the up-expression of miR-1764 in transfected SCs. Our findings suggest appropriate dose of exogenous 17β-estradiol treatment can ameliorate the inhibitory effect of metformin on SC proliferation via the regulation of AMPK/TSC2/mTOR signaling pathway, this might reduce the risk of poor male fertility caused by the abuse of anti-diabetic agents.
- Published
- 2021
4. Influence of freezing techniques and glycerol-based cryoprotectant combinations on the survival of testicular tissues from adult collared peccaries
- Author
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Andréia Maria da Silva, Alexandre Rodrigues Silva, Pierre Comizzoli, João Batista Freire Souza-Junior, Ana Gloria Pereira, Alexsandra Fernandes Pereira, Moacir Franco de Oliveira, Andreza Vieira Brasil, Luã Barbalho de Macêdo, and Carlos Eduardo Bezerra de Moura
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Glycerol ,Ethylene Glycol ,Cryoprotectant ,Sertoli cell proliferation ,Testicle ,Cryopreservation ,Andrology ,chemistry.chemical_compound ,Cryoprotective Agents ,Food Animals ,Freezing ,medicine ,Animals ,Dimethyl Sulfoxide ,Vitrification ,Viability assay ,Small Animals ,Artiodactyla ,Equine ,Chemistry ,Dimethyl sulfoxide ,medicine.anatomical_structure ,Animal Science and Zoology - Abstract
The objective of the study was to evaluate the effects of different cryopreservation techniques including glycerol-based cryoprotectant combinations on the structure and viability of testicular tissues from adult collared peccaries. Tissue biopsies (3.0 mm³) from 5 different individuals were allocated to 10 different groups: fresh control; slow freezing (SF), conventional vitrification (CV), or solid-surface vitrification (SSV); each of them using three different combinations of cryoprotectants [dimethyl sulfoxide (DMSO) + ethylene glycol (EG); DMSO + Glycerol; and EG + Glycerol]. After thawing/warming, samples were evaluated for histomorphology, viability, proliferative capacity potential, and DNA integrity. Most effective preservation of testicular histomorphology was achieved using SF and CV with DMSO + EG. However, the use of glycerol-based cryoprotectant combinations increased the occurrence of tubular cell swelling, tubular cell loss and shrinkage from the basal membrane. Cell viability was comparable among cryopreservation methods and cryoprotectant combinations. Regarding cell proliferative capacity, the use of SF with EG + Glycerol and SSV with DMSO + Glycerol impaired the conservation of spermatogonia proliferative potential compared to other treatments. Moreover, CV with DMSO + EG was better than SF with EG + Glycerol for Sertoli cell proliferation potential. Regarding DNA integrity, less damage occurred when using SF with DMSO + EG while more fragmentations were observed when using CV with EG + Glycerol or DMSO + Glycerol as well as SSV with EG + Glycerol or DMSO + Glycerol. In sum, SF and CV appeared to be the most suitable methods for the cryopreservation of adult peccary testicular tissues. Additionally, the use of glycerol-based cryoprotectant combinations did not improve testicular tissues preservation with DMSO + EG being the most efficient option.
- Published
- 2021
5. Homeobox transcription factor Meis1 is crucial to Sertoli cell mediated regulation of male fertility
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Alka Gupta, Umesh Rai, Rajesh Kumar Sarkar, Subeer S. Majumdar, Neetu Kunj, Rahul Pal, Neerja Wadhwa, Souvik Sen Sharma, and Kamal Mandal
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Male ,Infertility ,endocrine system ,Urology ,Endocrinology, Diabetes and Metabolism ,Sertoli cell proliferation ,Mice, Transgenic ,SOX9 ,Biology ,Male infertility ,Andrology ,Endocrinology ,medicine ,Animals ,Myeloid Ecotropic Viral Integration Site 1 Protein ,Spermatogenesis ,Sertoli Cells ,Sertoli cell ,medicine.disease ,Sperm ,Fertility ,medicine.anatomical_structure ,Reproductive Medicine ,Gene Knockdown Techniques ,Germ cell - Abstract
Background Infertility has become a global phenomenon and constantly declining sperm count in males in modern world pose a major threat to procreation of humans. Male fertility is critically dependent on proper functioning of testicular Sertoli cells. Defective Sertoli cell proliferation and/or impaired functional maturation may be one of the underlying causes of idiopathic male infertility. Using high-throughput "omics" approach, we found binding sites for homeobox transcription factor MEIS1 on the promoters of several genes up-regulated in pubertal (mature) Sertoli cells, indicating that MEIS1 may be crucial for Sertoli cell-mediated regulation of spermatogenesis at and after puberty. Objective To decipher the role of transcription factor MEIS1 in Sertoli cell maturation and spermatogenesis. Materials and methods Sc-specific Meis1 knockdown (KD) transgenic mice were generated using pronuclear microinjection. Morphometric and histological analysis of the testes from transgenic mice was performed to identify defects in spermatogenesis. Epididymal sperm count and litter size were analyzed to determine the effect of Meis1 knockdown on fertility. Results Sertoli cell (Sc)-specific Meis1 KD led to massive germ cell loss due to apoptosis and impaired spermatogenesis. Unlike normal pubertal Sc, the levels of SOX9 in pubertal Sc of Meis1 KD were significantly high, like immature Sc. A significant reduction in epididymal sperm count was observed in these mice. The mice were found to be infertile or sub-fertile (with reduced litter size), depending on the extent of Meis1 inhibition. Discussion The results of this study demonstrated for the first time, a role of Meis1 in Sc maturation and normal spermatogenic progression. Inhibition of Meis1 in Sc was associated with deregulated spermatogenesis and a consequent decline in fertility of the transgenic mice. Conclusions Our results provided substantial evidence that suboptimal Meis1 expression in Sc may be one of the underlying causes of idiopathic infertility.
- Published
- 2020
6. Nutrition affects Sertoli cell function but not Sertoli cell numbers in sexually mature male sheep.
- Author
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Yongjuan Guan, Guanxiang Liang, Hawken, Penny A. R., Meachem, Sarah J., Malecki, Irek A., Ham, Seungmin, Stewart, Tom, Le Luo Guan, and Martin, Graeme B.
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SERTOLI cells , *SERTOLI cell differentiation , *BODY mass index , *SPERMATOGENESIS in animals , *MAMMAL reproduction , *SPERMATOGENESIS - Abstract
We tested whether the reversible effects of nutrition on spermatogenesis in sexually mature sheep were mediated by Sertoli cells. Rams were fed with diets designed to achieve a 10% increase (High), no change (Maintenance) or a 10% decrease (Low) in body mass after 65 days. At the end of treatment, testes were lighter in the Low than the High group (P<0.01). The Maintenance group had intermediate values that were not significantly different from those of the other two groups. Spermatogenesis (Johnsen score) was impaired in the Low group, but normal in both other groups. There was no effect of treatment on Sertoli cell numbers, although 1% of Sertoli cells appeared to retain their ability to proliferate. By contrast, Sertoli cell function was affected by dietary treatment, as evidenced by differences between the High and Low groups (P<0.05) in the expression of seven Sertoli cell-specific genes. Under-nutrition appeared to reverse cellular differentiation leading to disruption of tight-junction morphology. In conclusion, in sexually mature sheep, reversible reductions in testis mass and spermatogenesis caused by under-nutrition were associated with impairment of basic aspects of Sertoli cell function but not with changes in the number of Sertoli cells. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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7. miR‐130a promotes immature porcine Sertoli cell growth by activating SMAD5 through the TGF‐β‐PI3K/AKT signaling pathway
- Author
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Bin Chen, Yao Chen, Xinyu Zeng, Dan Chu, Bo Weng, Anqi Yang, Maoliang Ran, Xiangwei Tang, and Hui Luo
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Male ,Smad5 Protein ,0301 basic medicine ,endocrine system ,Swine ,Sertoli cell proliferation ,Biology ,Biochemistry ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,Transforming Growth Factor beta ,microRNA ,Genetics ,medicine ,Animals ,Spermatogenesis ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Mice, Inbred ICR ,Sertoli Cells ,urogenital system ,Cell growth ,Akt/PKB signaling pathway ,Sertoli cell ,Cell biology ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Phosphorylation ,Proto-Oncogene Proteins c-akt ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Sertoli cells play vital roles in normal spermatogenesis, and microRNAs (miRNAs) participate in regulating Sertoli cell development. However, the functions and mechanisms of action of most identified miRNAs in porcine Sertoli cells remain largely unknown. Herein, we primarily explored the regulatory roles of miR-130a in immature porcine Sertoli cells using EdU-based high-content screening assay. The results demonstrated that 27 miRNAs have potential roles in the promotion of immature porcine Sertoli cell proliferation, and miR-130a was identified as a promising candidate. miR-130a promoted cell cycle progression and cell proliferation, whereas it impeded cell apoptosis in immature porcine Sertoli cells. It also contributed to Sertoli cell proliferation and testis development in vivo. A TMT-based proteomics approach revealed that miR-130a regulated the expression of 91 proteins and multiple pathways, including the TGF-β and PI3K/AKT signaling. miR-130a did not directly target the 3'-UTR of SMAD5; however, it increased SMAD5 phosphorylation. Moreover, miR-130a enhanced TGF-β signaling by activating SMAD5 protein, and TGF-β signaling further activated the PI3K/AKT signaling pathway to promote cell proliferation and inhibit cell apoptosis in porcine immature Sertoli cells. Collectively, miR-130a promoted immature porcine Sertoli cell growth by activating SMAD5 through the TGF-β-PI3K/AKT signaling pathway. This study, therefore, provides novel insights into the effects of miR-130a on porcine spermatogenesis through the regulation of immature Sertoli cell proliferation and apoptosis.
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- 2020
8. LncWNT3‐IT affects the proliferation of Sertoli cells by regulating the expression of the WNT3 gene in goat testis
- Author
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Qijie He, Lei Qiao, Zinuo Dai, Tianyuan Yang, Lina He, Zhongquan Zhao, Lingbin Liu, and Siyi Huang
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Male ,endocrine system ,Sertoli cell proliferation ,Biology ,Endocrinology ,Testis ,medicine ,Animals ,Viability assay ,Cell Proliferation ,Sertoli Cells ,medicine.diagnostic_test ,Cell growth ,Goats ,Wnt signaling pathway ,Sertoli cell ,Cell biology ,Wnt Proteins ,Blot ,medicine.anatomical_structure ,Animals, Newborn ,Gene Expression Regulation ,RNA, Long Noncoding ,Animal Science and Zoology ,Spermatogenesis ,Biotechnology ,Fluorescence in situ hybridization - Abstract
The proliferation and differentiation ability of testicular Sertoli cells directly affects spermatogenesis and male reproductive development. WNT proteins are involved in the regulation of cell proliferation, differentiation and spermatogenesis. Therefore, to study whether lncRNAs, which regulate the expression of WNT proteins during cell proliferation and differentiation, are worthwhile. In this study, testicular tissue from the Dazu black goat (Capra, goat, Chongqing, China) at neonatal time (less than 7 days old), early puberty time (45 days old) and sexual maturity time (90 days old) at three ages was subjected to high-throughput sequencing to predict testicular growth and development associated with WNT lncRNA. The final screening of lncWNT3-IT may be targeted to regulate the expression of WNT3. At the same time, the expression of WNT3 was verified by lncWNT3-IT by paraffin sectioning, fluorescence in situ hybridization, interference, overexpression, cytotoxicity assay, Western blotting and qPCR. The following results were obtained: lncWNT3-IT was expressed in the testicular Sertoli cells and played a role in the Sertoli cell cytoplasm. Fluorescence in situ hybridization localization analysis showed that lncWNT3-IT positively regulated the expression of WNT3, and through cell viability and cell proliferation experiments, it was found that the expression of lncWNT3-IT assisted in Sertoli cell proliferation. In summary, lncWNT3-IT can influence the proliferation of Sertoli cells by positively regulating the expression of WNT3.
- Published
- 2020
9. miR‐362 knock‐down promotes proliferation and inhibits apoptosis in porcine immature Sertoli cells by targeting the RMI1 gene
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Hui Luo, Bo Weng, Bin Chen, Maoliang Ran, Xiangwei Tang, Xinyu Zeng, Hu Gao, and Yao Chen
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Male ,endocrine system ,Swine ,Cell ,Sertoli cell proliferation ,Apoptosis ,Biology ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Cyclin D1 ,Annexin ,medicine ,Animals ,Cell Proliferation ,Sertoli Cells ,030219 obstetrics & reproductive medicine ,urogenital system ,Cell growth ,0402 animal and dairy science ,Gene Expression Regulation, Developmental ,04 agricultural and veterinary sciences ,Sertoli cell ,040201 dairy & animal science ,Cell biology ,MicroRNAs ,medicine.anatomical_structure ,Gene Knockdown Techniques ,Animal Science and Zoology ,Carrier Proteins ,Spermatogenesis ,Biotechnology - Abstract
Immature Sertoli cell proliferation determines the total number of mature Sertoli cells and further regulates normal spermatogenesis. Accumulating evidence demonstrates that microRNAs (miRNAs) play regulatory roles in immature Sertoli cell proliferation, while the functions and mechanisms of the Sertoli cells of domestic animals are poorly understood. In the present study, we aimed to investigate the roles of miR-362 in cell proliferation and apoptosis of porcine immature Sertoli cells. The results showed that miR-362 inhibition promoted the entrance of cells into the S phase and increased the expressions of cell cycle-related genes c-MYC, CNNE1, CCND1 and CDK4. Knock-down of miR-362 also promoted cell proliferation and inhibited apoptosis, which was demonstrated by the results from cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) and Annexin V-FITC/PI staining assays. The recQ-mediated genome instability protein 1 (RMI1) gene was identified as a potential target gene of miR-362 via luciferase reporter assay, and miR-362 repressed the protein expression of RMI1 in porcine immature Sertoli cells. siRNA-induced RMI1 knock-down further abolished the effects of miR-362 inhibition on porcine immature Sertoli cells. Collectively, we concluded that miR-362 knock-down promotes proliferation and inhibits apoptosis in porcine immature Sertoli cells by targeting the RMI1 gene, which indicates that miR-362 determines the fate of immature Sertoli cells.
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- 2020
10. MiRNA-34c Regulates Bovine Sertoli Cell Proliferation, Gene Expression, and Apoptosis by Targeting the AXL Gene
- Author
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Xibi Fang, Hao Sun, Ming Gao, Zitong Bai, Zhihui Zhao, Lixin Xia, Haibin Yu, Ping Jiang, and Runjun Yang
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endocrine system ,synthesis ,Veterinary medicine ,Sertoli cells ,proliferation ,Sertoli cell proliferation ,Article ,Receptor tyrosine kinase ,SF600-1100 ,microRNA ,Gene expression ,medicine ,Gene ,Reporter gene ,General Veterinary ,biology ,AXL ,urogenital system ,apoptosis ,Sertoli cell ,Cell biology ,medicine.anatomical_structure ,QL1-991 ,biology.protein ,Animal Science and Zoology ,miR-34c ,Zoology ,Spermatogenesis - Abstract
Simple Summary Fertility is one of the essential reproduction traits of bulls, and accurate prediction of fertility potential using a semen sample from a donor bull for artificial insemination is crucial to achieve consistently high reproductive efficiency. Somatic cells, such as Sertoli cells and Leydig cells, are important in testis formation and provide a nurturing and regulatory environment for spermatogenesis. Furthermore, it was suggested that non-coding RNAs, such as microRNAs, long non-coding RNAs, circular RNAs, and Piwi-interacting RNA, function as important regulators of gene expression at post-transcriptional level in spermatogenesis. In this study, microRNA-34c was verified to specifically regulate the AXL gene by targeting a sequence in the 3’ UTR; miRNA-34c can also influence the proliferation, apoptosis, and relative abundance of the transcript of male-reproduction-related genes. Therefore, microRNA-34c can be considered an essential regulator in the process of bull spermatogenesis. These results identify a key microRNA and functional genes in the process of cattle male reproduction, providing useful information for future marker-assisted selection of bulls with excellent sperm quality. Abstract MicroRNAs (miRNAs) play significant roles in mammalian spermatogenesis. Sertoli cells can provide a stable microenvironment and nutritional factors for germ cells, thus playing a vital role in spermatogenesis. However, few studies elucidate the regulation of bovine testicular Sertoli cells by miRNAs. Here, we have reported that miRNA-34c (miR-34c) regulates proliferation, apoptosis, and relative transcripts abundance gene in bovine Sertoli cells. In bovine Sertoli cells, overexpression of miR-34c inhibited proliferation and relative abundance of gene transcripts while promoting apoptosis of Sertoli cells, and the effects were the opposite when miR-34c was knocked down. Receptor tyrosine kinase (AXL) was identified as a direct target gene of miR-34c in Sertoli cells, validated by analysis of the relative abundance of AXL transcript and dual-luciferase reporter assay. The relative abundance of the transcript of genes related to male reproduction in Sertoli cells was changed after the AXL gene was overexpressed, as demonstrated by the RT2 Profiler PCR Array results. In summary, miR-34c specifically regulated the AXL gene by targeting a sequence in the 3′-UTR, which could influence proliferation, apoptosis, and relative abundance of the transcript of male reproduction-related genes. Therefore, miR-34c could be considered an essential regulator in the process of bull spermatogenesis.
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- 2021
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11. Assessment of estradiol-induced gene regulation and proliferation in an immortalized mouse immature Sertoli cell line.
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Kumar, Narender, Srivastava, Swati, Burek, Malgorzata, Förster, Carola Y., and Roy, Partha
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SERTOLI cells , *ESTRADIOL , *GENETIC regulation , *CELL proliferation , *LABORATORY mice , *CELL culture - Abstract
Aims The number of Sertoli cells during proliferative phase determines the fate of the germ cells in male reproductive system. A well-characterized cell line may help in better understanding of Sertoli cell biology. Hence, the present study assessed estradiol signaling in a mouse immature Sertoli cell line (MSC-1) as an alternative model in place of primary culture of Sertoli cells. Main methods In this study, we used MSC-1 cell line, derived from 10-day old mice. The cell cycle parameters were assessed, and the expression and regulation of Sertoli cell-specific secretory genes ( ABP ; androgen-binding protein ) and tight junction genes ( claudin-5 , occludin , and vimentin ) in response to estradiol was studied. Key findings The results obtained suggested the presence of both estrogen receptors (ERα and ERβ) in MSC-1 cells. In vitro scratch assay and cell-cycle analysis suggested the proliferative effects of estradiol in both time- and dose-dependent manner. The gene expression profiles of ABP , claudin-5 , and occludin showed biphasic regulation at low and high doses of estradiol. Analysis of signaling pathways suggested the activation of extracellular signal-regulated kinase (ERK) pathway with significantly increased pERK/ERK ratio ( p < 0.05). The results also suggested down regulation in the expression of mir-17 family members (mir-17, mir-20b, and mir-106a) ( p < 0.05). Significance Considering the limited number of Sertoli cell lines and long-term survival inability of primary culture of Sertoli cells, MSC-1 cells could be a potential cell line for understanding the mechanisms of various cellular events in Sertoli cells. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
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12. Causes of hypogonadotropic hypogonadism predict response to gonadotropin substitution in adults.
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Rohayem, J., Sinthofen, N., Nieschlag, E., Kliesch, S., and Zitzmann, M.
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HYPOGONADISM , *GONADOTROPIN , *HORMONE therapy , *DRUG efficacy , *SPERM count , *CONCEPTION , *SPERMATOGENESIS , *THERAPEUTICS - Abstract
Germ cell and Sertoli cell proliferation and maturation in human testes occur in three main waves, during the late fetal and early neonatal period and at early puberty. They are triggered by periods of increased activity of the hypothalamic-pituitary-gonadal ( HPG) axis. In hypogonadotropic hypogonadism ( HH), these processes are variably disturbed. The objective of this study was to explore whether success of gonadotropin replacement in HH men is predictable by the origin of HH, indicating time of onset and severity of Gn RH/gonadotropin deficiency. The data of 51 adult HH patients who had undergone one cycle of hCG/ FSH treatment were reviewed. Five groups were established, according to the underlying HH origin. Therapeutic success by final bi-testicular volumes ( BTVs) final sperm concentrations ( SC) and conception rates were compared and related to baseline parameters, indicative of the degree of HPG-axis disruption. Overall, BTVs rose from 13 ± 15 to 27 ± 15 mL, spermatogenesis was induced in 98%, with mean SCs of 15 ± 30 mill/mL, spontaneous pregnancies in 37% and additional 18% via intracytoplasmic sperm injection. Kallmann syndrome patients had the poorest responses ( BTV: 16.9 ± 10 mL; SC: 3.5 ± 5.6 mill/mL), followed by patients with congenital/infancy-acquired multiple pituitary hormone deficiencies ( MPHD) and patients with HH+absent puberty ( BTV: 21 ± 14/24 ± 9 mL; SC: 5.5 ± 6.5/ 14.5 ± 23.8 mill/mL). HH men with pubertal arrest and with post-pubertally acquired MPHD had the best results ( BTV: 36 ± 14/38 ± 16 mL; SC: 25.4 ± 34.2/29.9 ± 50.5 mill/mL). Earlier conception after 20.3 ± 11.5 months (vs. 43.1 ± 43.8; p = 0.047) of gonadotropin treatment with higher pregnancy rates (62% vs. 42%) was achieved in the two post-pubertally acquired HH subgroups, compared to the three pre-pubertally acquired. Therapeutic success was higher in patients without previously undescended testes, with higher baseline BTVs (pre- vs. post-pubertal HH: 5 ± 4 mL vs. 26 ± 16 mL; p < 0.0001) and higher baseline inhibinB levels (pre- vs. post-pubertal HH: 16.6 vs. 144.5 pg/mL; p = 0.0004). The cause of HH is a valuable predictor of outcome of gonadotropin replacement in adults. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
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13. The Molecular Mechanism of Sex Hormones on Sertoli Cell Development and Proliferation
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Basit Shah, Ranjha Khan, Wasim Shah, Wei Liu, Jie Wen, Asad Khan, Xiaohua Jiang, and Sobia Dil
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Male ,0301 basic medicine ,Somatic cell ,Sertoli cells ,Endocrinology, Diabetes and Metabolism ,Sertoli cell proliferation ,Review ,Mice ,Endocrinology ,0302 clinical medicine ,Sex hormone-binding globulin ,Testosterone ,Gonadal Steroid Hormones ,Progesterone ,fertility ,Cell Differentiation ,Sertoli cell ,Activins ,Cell biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cytokines ,Signal Transduction ,Thyroid Hormones ,endocrine system ,Tretinoin ,testis ,Biology ,Diseases of the endocrine glands. Clinical endocrinology ,sex hormone ,03 medical and health sciences ,Paracrine signalling ,medicine ,Animals ,Humans ,Endocrine system ,Inhibins ,Cell Proliferation ,urogenital system ,Estrogens ,Luteinizing Hormone ,RC648-665 ,Receptor, Insulin ,spermatogenesis ,Prolactin ,Rats ,Wnt Proteins ,030104 developmental biology ,biology.protein ,Follicle Stimulating Hormone ,Spermatogenesis ,Hormone - Abstract
Sustaining and maintaining the intricate process of spermatogenesis is liable upon hormones and growth factors acting through endocrine and paracrine pathways. The Sertoli cells (SCs) are the major somatic cells present in the seminiferous tubules and are considered to be the main regulators of spermatogenesis. As each Sertoli cell supports a specific number of germ cells, thus, the final number of Sertoli cells determines the sperm production capacity. Similarly, sex hormones are also major regulators of spermatogenesis and they can determine the proliferation of Sertoli cells. In the present review, we have critically and comprehensively discussed the role of sex hormones and some other factors that are involved in Sertoli cell proliferation, differentiation and maturation. Furthermore, we have also presented a model of Sertoli cell development based upon the recent advancement in the field of reproduction. Hence, our review article provides a general overview regarding the sex hormonal pathways governing Sertoli cell proliferation and development.
- Published
- 2021
14. Three-dimensional structure of testis cords in mice and rats
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Hiroki Nakata, Masahiro Itoh, Shoichi Iseki, Takuya Omotehara, and Atsushi Mizokami
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Male ,Models, Anatomic ,Cord ,Gonad ,Urology ,Endocrinology, Diabetes and Metabolism ,Sertoli cell proliferation ,Biology ,03 medical and health sciences ,Tunica albuginea (ovaries) ,Mice ,0302 clinical medicine ,Endocrinology ,Imaging, Three-Dimensional ,Rete testis ,Paraffin section ,Testis ,medicine ,Animals ,Cell Proliferation ,Spermatic Cord ,030219 obstetrics & reproductive medicine ,Sertoli Cells ,Anatomy ,Branching points ,Rats ,Seminiferous tubule ,medicine.anatomical_structure ,Reproductive Medicine ,Models, Animal - Abstract
Background Testis cord elongation and coiling, which occur in the final stage of testis formation, have been attributed to Sertoli cell proliferation; however, the underlying mechanisms remain unclear. Objective The aim of the present study was to clarify the precise three-dimensional (3D) structure of testis cords in the final stage of testis formation in mice and rats. Materials and methods We reconstructed whole testis cords in the final stage of testis formation in mice (on embryonic day (E) 15.5 and E18.5) and rats (on E16.5 and E19.5) using serial paraffin sections and high-performance 3D reconstruction software. Results Detailed morphometric parameters were calculated for 3D-reconstructed testis cords in 6 mouse and rat testes each. The mean numbers of testis cords in mice and rats were 12.7 and 27.8, respectively. The mean number of branching points per testis cord was 1.52 in mice, whereas it was only 0.30 in rats. In contrast, the mean ratio of the inner cords, i.e., cords not in contact with the tunica albuginea, was 23.0% in rats, whereas it was only 6.5% in mice. In both species, the cords on the cranial side coiled more strongly than those on the caudal side, consistent with the greater expansion of the testis volume on the caudal side. All cords formed right-handed helices from the rete testis side. Discussion and conclusions The present results suggest that testis cords undergo anastomosis at a higher frequency in mice than in rats and that the coiling of testis cords proceeds from the cranial to caudal side of the testis in both species. This article is protected by copyright. All rights reserved.
- Published
- 2021
15. TBC1D20 deficiency induces Sertoli cell apoptosis by triggering irreversible endoplasmic reticulum stress in mice
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Jing Yu, Jing Ye, Yanli Gu, Lina Cui, Wen-Lin Chang, Yaoting Gui, Minghua Li, Fangting Zhang, Zeng Zhang, and Qian Ma
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Male ,endocrine system ,Embryology ,Golgi Apparatus ,Sertoli cell proliferation ,Spermatogenesis arrest ,Apoptosis ,Mice, Transgenic ,Biology ,Endoplasmic Reticulum ,Mice ,symbols.namesake ,Genetics ,medicine ,Animals ,Spermatogenesis ,Molecular Biology ,Caspase 12 ,Infertility, Male ,Cell Proliferation ,Sertoli Cells ,urogenital system ,Endoplasmic reticulum ,Obstetrics and Gynecology ,Cell Biology ,Golgi apparatus ,Endoplasmic Reticulum Stress ,Sertoli cell ,G1 Phase Cell Cycle Checkpoints ,Cell biology ,rab1 GTP-Binding Proteins ,medicine.anatomical_structure ,Reproductive Medicine ,symbols ,Germ cell ,Developmental Biology - Abstract
Male ‘blind sterile’ mice with the causative TBC1 domain family member 20 (TBC1D20) deficiency are infertile with excessive germ cell apoptosis and spermatogenesis arrest at the spermatid stage. Sertoli cells are characterised as ‘nurse cells’ essential for normal spermatogenesis, but the role and corresponding molecular mechanisms of TBC1D20 deficiency in Sertoli cells of mice are not clear to date. In the present study, the histopathology of the testis and Sertoli cell proliferation and apoptosis were determined, and the corresponding molecular mechanisms were investigated by western blotting. Our data showed that TBC1D20 exhibits a testis-abundant expression pattern, and its expression level is positively associated with spermatogenesis. TBC1D20 is assembled in the Golgi and endoplasmic reticulum and is widely expressed by various germ cell subtypes and Sertoli cells. TBC1D20 deficiency in Sertoli cells led to an excessive apoptosis ratio and G1/S arrest. The increased apoptosis of TBC1D20-deficient Sertoli cells resulted from caspase-12 activation. TBC1D20-deficient Sertoli cells had an abnormal Golgi-endoplasmic reticulum structure, which led to endoplasmic reticulum stress, resulting in cell cycle arrest and excessive apoptosis. It suggested that TBC1D20 deficiency triggers irreversible endoplasmic reticulum stress resulting in G1/S arrest and excessive apoptosis in TBC1D20-deficient Sertoli cells, and TBC1D20 deficiency in Sertoli cells may also contribute to the infertility phenotype in ‘blind sterile’ male mice.
- Published
- 2019
16. miR-10b promotes porcine immature Sertoli cell proliferation by targeting the DAZAP1 gene
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Rong Cao, Anqi Yang, Bin Chen, Hu Gao, Hui Luo, Maoliang Ran, Xiangwei Tang, Fuzhi Peng, and Bo Weng
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0106 biological sciences ,endocrine system ,proliferation ,Agriculture (General) ,Sertoli cell proliferation ,Plant Science ,Biology ,01 natural sciences ,Biochemistry ,S1-972 ,DAZAP1 ,Food Animals ,microRNA ,Gene expression ,medicine ,porcine immature Sertoli cell ,Gene ,Messenger RNA ,Ecology ,urogenital system ,04 agricultural and veterinary sciences ,Sertoli cell ,Cell biology ,medicine.anatomical_structure ,Apoptosis ,040103 agronomy & agriculture ,gene expression ,0401 agriculture, forestry, and fisheries ,Animal Science and Zoology ,Agronomy and Crop Science ,Spermatogenesis ,miR-10b ,010606 plant biology & botany ,Food Science - Abstract
MicroRNAs (miRNAs) have been widely identified in porcine testicular tissues and implicated as crucial regulators of proliferation, apoptosis, and differentiation in porcine spermatogenesis related cells. However, the function roles of most of the miRNAs that have been identified in Sertoli cells are poorly understood. In the present study, six experiments were conducted to study the regulatory role of miR-10b in porcine immature Sertoli cells. In experiment 1, the results showed that the relative mRNA expression level of miR-10b in porcine testicular tissues decreased quadratically (P0.05) on porcine immature Sertoli cell apoptosis. In experiment 6, the co-transfection treatment results showed that miR-10b promoted (P
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- 2019
17. Are testicular cortisol and WISP2 involved in estrogen-regulated Sertoli cell proliferation?
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Trish Berger, Heidi Kucera, Simin Tang, and Puneet Sidhu
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Male ,endocrine system ,medicine.medical_specialty ,Sex Differentiation ,Hydrocortisone ,Swine ,medicine.drug_class ,Gene Expression ,Sertoli cell proliferation ,Endogeny ,Biology ,Dexamethasone ,CCN Intercellular Signaling Proteins ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Food Animals ,Internal medicine ,Testis ,medicine ,Animals ,Fulvestrant ,Cell Proliferation ,Sertoli Cells ,030219 obstetrics & reproductive medicine ,urogenital system ,0402 animal and dairy science ,Estrogens ,04 agricultural and veterinary sciences ,General Medicine ,Sertoli cell ,Spermatozoa ,040201 dairy & animal science ,medicine.anatomical_structure ,Estrogen ,Letrozole ,Animal Science and Zoology ,Signal transduction ,Spermatogenesis ,hormones, hormone substitutes, and hormone antagonists ,Glucocorticoid ,medicine.drug - Abstract
The number of Sertoli cells has a major effect on adult testis size and sperm production capacity. Mechanisms that regulate the number of Sertoli cells in livestock are at best nebulously understood; however, with lesser testicular estrogen production, proliferation of Sertoli cells is prolonged compared with vehicle-treated littermates. Decreased WISP2 gene expression in testes as a result of less endogenous estrogen is similar to altered WISP2 gene expression following corticosteroid treatment of some cultured cells. Taken together, these findings indicate decreased testicular cortisol might be in the signaling pathway between reduced endogenous estrogens and the prolonged interval of Sertoli cell proliferation. Hence, in these studies, potential actions of testicular corticosteroid on Sertoli cell numbers were evaluated. Testicular cortisol concentrations were reduced at 6.5 weeks of age (P 0.05) in littermates treated with the aromatase inhibitor, letrozole, compared with littermates treated with vehicle. Letrozole treatment leads to reduced testicular estradiol and greater Sertoli cell numbers during the early juvenile interval in pigs. The inverse relationship between testicular glucocorticoid and Sertoli cell proliferation was also tested by increasing local testicular glucocorticoids using the synthetic compound, dexamethasone. Local administration beginning at 1.5 weeks of age (osmotic pump and catheter (n = 3) or a silastic implant (n = 5)) reduced Sertoli cell numbers at 6.5 weeks of age compared with littermates that received the vehicle treatment (P0.05). In summary, testicular glucocorticoid concentration was inversely correlated with Sertoli cell numbers during the first wave of Sertoli cell proliferation.
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- 2019
18. Npat ‐dependent programmed Sertoli cell proliferation is indispensable for testis cord development and germ cell mitotic arrest
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Shi Yin, Furhan Iqbal, Jianqiang Bao, Suixing Fan, Juan Xu, Yuanwei Zhang, Yuying Jiao, Asim Ali, Qinghua Shi, and Xiaohua Jiang
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0301 basic medicine ,endocrine system ,urogenital system ,Cell growth ,Somatic cell ,Sertoli cell proliferation ,Biology ,Sertoli cell ,Biochemistry ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Mitotic cell cycle ,Gonocyte ,Genetics ,medicine ,Molecular Biology ,Mitosis ,030217 neurology & neurosurgery ,Germ cell ,Biotechnology - Abstract
As the major somatic cell type, Sertoli cells undergo active proliferation and play essential roles to establish testis cord at fetal stage. They also function to maintain germ cell development throughout the life of testicular development. However, the significance of Sertoli cell number for testis cord development and gonocyte fate is still unclear. Nuclear protein ataxia-telangiectasia (NPAT, also known as p220), a substrate of cyclin E/cyclin-dependent kinase 2, is well known as a regulator of cell proliferation through regulating histone expression. To study the role of NPAT during Sertoli cell development, we generated a mouse strain carrying conditional floxed Npat alleles, when crossing with anti-Mullerian hormone-cre, leading to the specific deletion of Npat in Sertoli cells. Npat disruption in Sertoli cells inhibited the programmed proliferation of fetal Sertoli cells resulting in disruption of developing testis cords, and subsequent postnatal mutant testes were severely hypoplastic. Germ cells, which are presumed to be in quiescent status during perinatal stage, exited G0 phase arrest and re-enter mitotic cell cycle prematurely. Of particular note, some germ cells possessed the meiotic signal in Npat-deficient testes. Our data thus indicates that the function of Npat-dependent Sertoli cells is essential at multiple steps in testis development, and this study also identifies Sertoli cells as a major regulator of germ cell development, which are required to maintain a local growth niche to repress premature mitosis and meiosis of gonocytes.-Jiang, X., Yin, S., Fan, S., Bao, J., Jiao, Y., Ali, A., Iqbal, F., Xu, J., Zhang, Y., Shi, Q. Npat-dependent programmed Sertoli cell proliferation is indispensable for testis cord development and germ cell mitotic arrest.
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- 2019
19. miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin Signaling
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Qingqing Yuan, Chencheng Yao, Zijue Zhu, Xue Yunjing, Chao Yang, Liangyu Zhao, Zheng Li, Ruhui Tian, Yuhua Huang, Peng Li, Huixing Chen, Yuehua Gong, Zuping He, Hong Wang, and Erlei Zhi
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LRP6 ,0301 basic medicine ,endocrine system ,Small interfering RNA ,synthesis ,Sertoli cell proliferation ,Article ,03 medical and health sciences ,0302 clinical medicine ,Cyclin D1 ,Drug Discovery ,medicine ,proliferation and apoptosis ,Wnt/β-catenin ,urogenital system ,Chemistry ,Cell growth ,lcsh:RM1-950 ,Wnt signaling pathway ,human Sertoli cells ,Sertoli cell ,miR-202-3p ,Cell biology ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Molecular Medicine ,Signal transduction - Abstract
MicroRNAs (miRNAs) play important roles in mammalian spermatogenesis, which is highly dependent on Sertoli cells. However, the functions and mechanisms of miRNAs in regulating human Sertoli cells remain largely unknown. Here, we report that hsa-miR-202-3p mediates the proliferation, apoptosis, and synthesis function of human Sertoli cells. miR-202-3p was upregulated in Sertoli cells of Sertoli cell-only syndrome (SCOS) patients compared with obstructive azoospermia (OA) patients with normal spermatogenesis. Overexpression of miR-202-3p induced Sertoli cell apoptosis and inhibited cell proliferation and synthesis, and the effects were opposite when miR-202-3p was knocked down. Lipoprotein receptor-related protein 6 (LRP6) and Cyclin D1 of the Wnt/β-catenin signaling pathway were identified as direct targets of miR-202-3p in Sertoli cells, which were validated by bioinformatics tools and dual-luciferase reporter assay. Differentially expressed LRP6 and Cyclin D1 between OA and SCOS Sertoli cells were also verified. LRP6 small interfering RNA (siRNA) interference not only mimicked the effects of miR-202-3p overexpression, but also antagonized the effects of miR-202-3p inhibition on Sertoli cells. Collectively, miR-202-3p controls the proliferation, apoptosis, and synthesis function of human Sertoli cells via targeting LRP6 and Cyclin D1 of the Wnt/β-catenin signaling pathway. This study thus provides a novel insight into fate determinations of human Sertoli cells and niche of human testis. Keywords: human Sertoli cells, miR-202-3p, proliferation and apoptosis, synthesis, LRP6, Cyclin D1, Wnt/β-catenin
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- 2019
20. Postnatal testis development in the collared peccary (Tayassu tajacu), with emphasis on spermatogonial stem cells markers and niche
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Diva Anelie de Araújo Guimarães, Gleide F. Avelar, Luiz R. França, Guilherme M.J. Costa, and Nathalia de Lima e Martins Lara
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Male ,endocrine system ,Sertoli cell proliferation ,030209 endocrinology & metabolism ,Biology ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Gonocyte ,Testis ,medicine ,Animals ,Stem Cell Niche ,Spermatogenesis ,Artiodactyla ,030304 developmental biology ,0303 health sciences ,Fetus ,Sertoli Cells ,Leydig cell ,Stem Cells ,Body Weight ,Organ Size ,Seminiferous Tubules ,Sertoli cell ,Sperm ,Hormones ,Spermatogonia ,Phenotype ,medicine.anatomical_structure ,Cytoarchitecture ,Animal Science and Zoology ,Biomarkers ,Germ cell - Abstract
Collared peccaries (Tayassu tajacu) present a unique testis cytoarchitecture, where Leydig cells (LC) are mainly located in cords around the seminiferous tubules (ST) lobes. This peculiar arrangement is very useful to better investigate and understand the role of LC in spermatogonial stem cells (SSCs) biology and niche. Recent studies from our laboratory using adult peccaries have shown that the undifferentiated type A spermatogonia (Aund or SSCs) are preferentially located in ST regions adjacent to the intertubular compartment without LC. Following these studies, our aims were to investigate the collared peccary postnatal testis development, from birth to adulthood, with emphasis on the establishment of LC cytoarchitecture and the SSCs niche. Our findings demonstrated that the unique LC cytoarchitecture is already present in the neonate peccary's testis, indicating that this arrangement is established during fetal development. Based on the most advanced germ cell type present at each time period evaluated, puberty (the first sperm release in the ST lumen) in this species was reached at around one year of age, being preceded by high levels of estradiol and testosterone and the end of Sertoli cell proliferation. Almost all gonocytes and SSCs expressed Nanos1, Nanos2 and GFRA1. The analysis of SSCs preferential location indicated that the establishment of SSCs niche is coincident with the occurrence of puberty. Taken together, our findings reinforced and extended the importance of the collared peccary as an animal model to investigate testis function in mammals, particularly the aspects related to testis organogenesis and the SSCs biology and niche.
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- 2019
21. Tumor Suppressor PTEN Regulates Negatively Sertoli Cell Proliferation, Testis Size, and Sperm Production In Vivo
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Françoise Kühne, Yasmine Neirijnck, Pauline Sararols, Serge Nef, Michelangelo Foti, Nina Atanassova, Chloé Mayère, and Ekaterina Pavlova
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Male ,0301 basic medicine ,endocrine system ,medicine.medical_specialty ,Sertoli cell proliferation ,030209 endocrinology & metabolism ,Biology ,Receptor, IGF Type 1 ,Mice ,03 medical and health sciences ,Paracrine signalling ,0302 clinical medicine ,Endocrinology ,Somatomedins ,Internal medicine ,Testis ,medicine ,Animals ,PTEN ,ddc:576.5 ,Progenitor cell ,ddc:612 ,Spermatogenesis ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Insulin-like growth factor 1 receptor ,Sertoli Cells ,urogenital system ,PTEN Phosphohydrolase ,Sertoli cell ,Receptor, Insulin ,Cell biology ,Insulin receptor ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein - Abstract
The IGFs are the major intratesticular factors regulating immature Sertoli cell proliferation and are, therefore, critical to establish the magnitude of sperm production. However, the intratesticular source of IGF production and the downstream signaling pathway mediating IGF-dependent Sertoli cell proliferation remain unclear. Single-cell RNA sequencing on mouse embryonic testis revealed a robust expression of Igf1 and Igf2 in interstitial steroidogenic progenitors, suggesting that IGFs exert paracrine actions on immature Sertoli cells. To elucidate the intracellular signaling mechanism that underlies the proliferative effects of IGFs on immature Sertoli cells, we have generated mice with Sertoli cell-specific deletion of the Pten gene, a negative regulator of the phosphatidylinositol-3 kinase (PI3K)/AKT pathway, alone or together with the insulin receptor (Insr) and the IGF1 receptor (Igf1r). Although ablation of Pten appears dispensable for Sertoli cell proliferation and spermatogenesis, inactivation of Pten in the absence of Insr and Igf1r rescued the Sertoli cell proliferation rate during late fetal development, testis size, and sperm production. Overall, these findings suggest that IGFs secreted by interstitial progenitor cells act in a paracrine fashion to promote the proliferation of immature Sertoli cells through the IGF/PTEN/PI3K pathway.
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- 2018
22. MicroRNA-125a-5p modulates the proliferation and apoptosis of TM4 Sertoli cells by targeting RAB3D and regulating the PI3K/AKT signaling pathway
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Fengmeng Teng, Fang Hu, and Maosen Zhang
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Male ,endocrine system ,Embryology ,rab3 GTP-Binding Proteins ,Sertoli cell proliferation ,Apoptosis ,Biology ,Cell Line ,Mice ,Phosphatidylinositol 3-Kinases ,Downregulation and upregulation ,microRNA ,Genetics ,medicine ,Animals ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Gene knockdown ,Sertoli Cells ,urogenital system ,Akt/PKB signaling pathway ,Obstetrics and Gynecology ,Cell Biology ,Sertoli cell ,Cell biology ,MicroRNAs ,medicine.anatomical_structure ,Reproductive Medicine ,Gene Expression Regulation ,Proto-Oncogene Proteins c-akt ,Developmental Biology ,Signal Transduction - Abstract
Sertoli cells provide protection and nutrition for developing sperm. Each stage of sperm development occurs on the surface of Sertoli cells. MicroRNA (MiR)-125a-5p is involved in male reproduction. The current research aimed to probe the role of miR-125a-5p in Sertoli cell function. Functionally, miR-125a-5p knockdown facilitated Sertoli cell proliferation, while miR-125a-5p overexpression suppressed Sertoli cell proliferation, as evidenced by 5-ethynyl-20-deoxyuridine incorporation assay. Additionally, miR-125a-5p knockdown inhibited Sertoli cell apoptosis, while miR-125a-5p upregulation facilitated Sertoli cell apoptosis, as evidenced by flow cytometry analysis. Computationally, we identified four predicted mRNA targets of miR-125a-5p. Based on the results of luciferase reporter assay, miR-125a-5p was confirmed to bind to the predicted sequence in the Ras-related protein Rab-3D (RAB3D) 3’UTR. Rescue experiments showed that miR-125a-5p suppressed the proliferative ability of TM4 Sertoli cells and facilitated their apoptosis by targeting RAB3D. Finally, our data confirmed that miR-125a-5p and RAB3D modulated activation of the PI3K/AKT pathway. In conclusion, our data showed that miR-125a-5p regulated Sertoli cell proliferation and apoptosis by targeting RAB3D and regulating the PI3K/AKT pathway.
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- 2021
23. Thyroid hormones, Sertoli cell proliferation and differentiation in progenies from carbamazepine‐treated rat dams during pregnancy and lactation
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Sandra Maria Miraglia, Joana Noguères Simas, Camila Cicconi Paccola, Renato Borges Tesser, Samara Urban de Oliva, and Rhaiza Roberta Andretta
- Subjects
Male ,Thyroid Hormones ,endocrine system ,medicine.medical_specialty ,Offspring ,Urology ,030232 urology & nephrology ,Sertoli cell proliferation ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Pregnancy ,Internal medicine ,Lactation ,medicine ,Animals ,Cell Proliferation ,Sertoli Cells ,030219 obstetrics & reproductive medicine ,Cell Differentiation ,General Medicine ,Carbamazepine ,Sertoli cell ,medicine.disease ,Rats ,medicine.anatomical_structure ,Gestation ,Female ,Homeostasis ,medicine.drug - Abstract
Carbamazepine (CBZ) is used in the control of seizure and affective disorders, causing hypothyroidism. Thyroid hormones regulate the Sertoli cell proliferation and differentiation. Clinical aspects must be considered since epileptic fertile women need to continuously use CBZ during pregnancy and lactation. This study aimed to evaluate the effects of CBZ on testis development of rat offspring from dams treated during pregnancy/lactation. Rat dams received CBZ (20 mg kg-1 day-1 ) or vehicle by intra-peritoneal route during gestation and lactation. Progenies were euthanised at 4, 14, 41, 63 and 93-days post-partum (dpp) for the evaluation of T3, T4 and TSH plasma total levels. Testicular cross sections were submitted to anti-Ki67, anti-PCNA, anti-p27kip1 and anti-transferrin immunolabelling for the evaluation of Sertoli cells. There was a significant reduction in p27kip1 -positive Sertoli cell numerical densities and an increase in TSH level at 14 dpp. CBZ exposure affected the volume density of transferrin-positive immunolabelling at 63 dpp. These results suggest that CBZ may cause a dysregulation of the controller system of thyroid hormones homeostasis leading to an increase in the proliferation rate at the neonatal phase and a differentiation delay of the Sertoli cell, culminating in an altered function at late puberty. The occurrence of hypothyroidism cannot be completely discarded.
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- 2021
24. Postnatal metformin treatment alters rat Sertoli cell proliferation and daily sperm production
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Agostina Gorga, Vanina Gabriela Da Ros, Maria Noel Lujan Galardo, Gustavo Marcelo Rindone, Mariano G. Buffone, Maria Fernanda Riera, Eliana Herminia Pellizzari, María del Carmen Camberos, and Silvina Beatriz Meroni
- Subjects
AMPK ,Male ,endocrine system ,METFORMIN ,Urology ,Endocrinology, Diabetes and Metabolism ,Drug Evaluation, Preclinical ,Sertoli cell proliferation ,Biology ,purl.org/becyt/ford/1 [https] ,Andrology ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Cyclin D1 ,Pregnancy ,CELL CYCLE REGULATORS ,Gene expression ,medicine ,Animals ,Hypoglycemic Agents ,purl.org/becyt/ford/1.6 [https] ,Spermatogenesis ,SERTOLI CELLS ,Cell Proliferation ,DAILY SPERM PRODUCTION ,030219 obstetrics & reproductive medicine ,Sertoli Cells ,urogenital system ,PROLIFERATION ,Cell cycle ,Sertoli cell ,Sperm ,Metformin ,medicine.anatomical_structure ,Reproductive Medicine ,Animals, Newborn ,Female ,medicine.drug - Abstract
The direct correlation between Sertoli cell number and sperm production capacity highlights the importance of deciphering external factors that modify Sertoli cell proliferation. A growing body of evidence in vitro suggests that metformin, the main pharmacological agent for type 2 diabetes treatment in children, exerts anti-proliferative effects on Sertoli cells. Fil: Rindone, Gustavo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Gorga, Agostina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Pellizzari, Eliana Herminia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Camberos, Maria del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Galardo, Maria Noel Lujan. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Da Ros, Vanina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Buffone, Mariano Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Meroni, Silvina Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Riera, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
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- 2020
25. Neonatal maternal separation increases the number of p27-positive Sertoli cells in prepuberty
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Kenta Nagahori, Xi Wu, Masahiro Itoh, Shinichi Kawata, Hidenobu Miyaso, Yuki Ogawa, Miyuki Kuramasu, Zhong-Lian Li, and Kaiya Takano
- Subjects
Male ,endocrine system ,Early life stress ,Sertoli cell proliferation ,010501 environmental sciences ,Biology ,Toxicology ,01 natural sciences ,Andrology ,03 medical and health sciences ,Mice ,Prepuberty ,Testis ,medicine ,Animals ,Testosterone ,Spermatogenesis ,030304 developmental biology ,0105 earth and related environmental sciences ,Cell Proliferation ,0303 health sciences ,Sertoli Cells ,Estradiol ,Kinase ,Maternal Deprivation ,Seminiferous Tubules ,Sertoli cell ,Spermatozoa ,Epithelium ,medicine.anatomical_structure ,Seminiferous tubule ,Follicle Stimulating Hormone - Abstract
Neonatal maternal separation (NMS) is an experimental model for early life stress, which affects the growth and development of various organs, resulting in adverse health effects in humans and animals. In our previous study, we demonstrated that NMS [(0.5-, 1-, 2-h/day NMS, from postnatal day (PND) 1-10] induced morphological changes to the male reproductive system, including decreased Sertoli cell numbers in mouse testes at PND 70. To clarify the mechanism by which NMS decreases Sertoli cell numbers, we evaluated the effects of NMS on mouse testes at PNDs 10 and 16. At PND 10, the Sertoli cell number was not significantly different among experimental groups; however, it decreased in 0.5- and 2-h/day NMS mice at PND 16. The termination of Sertoli cell proliferation in prepuberty can be induced by p27, a cyclin-dependent kinase inhibitor. At PND 10, we observed an increase in the number of p27-positive Sertoli cells in 2-h/day NMS mice. The seminiferous tubule diameters decreased significantly in 1- and 2-h/day NMS mice, and the relative interstitial area increased in 2-h/day NMS mice. Serum corticosterone level significantly increased, and serum testosterone level significantly decreased in the 2-h/day NMS mice. At PND 16, the tubule diameters and height of seminiferous epithelium were significantly higher in 0.5- and 2-h/day NMS mice. Our results suggest that NMS disturbs serum corticosterone and testosterone levels and increases the number of p27-positive Sertoli cells at PND 10, resulting in a decrease in the number of Sertoli cells at PND 16.
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- 2020
26. E4 Transcription Factor 1 (E4F1) Regulates Sertoli Cell Proliferation and Fertility in Mice
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Qi-En Yang, Qi-Lin Yang, and Rong-Ge Yan
- Subjects
endocrine system ,Spermiogenesis ,Somatic cell ,proliferation ,Population ,sertoli cells ,Sertoli cell proliferation ,Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Conditional gene knockout ,lcsh:Zoology ,medicine ,lcsh:QL1-991 ,education ,030304 developmental biology ,fertility ,0303 health sciences ,education.field_of_study ,030219 obstetrics & reproductive medicine ,lcsh:Veterinary medicine ,General Veterinary ,urogenital system ,Sertoli cell ,spermatogenesis ,Cell biology ,E4F1 ,medicine.anatomical_structure ,lcsh:SF600-1100 ,Animal Science and Zoology ,Spermatogenesis ,Germ cell - Abstract
Simple Summary Male fertility relies on the generation of functional sperm in seminiferous tubules of the testis. In mammals, Sertoli cells are the only somatic cells that directly interact with spermatogenic cells. Compelling evidences suggest that the number of Sertoli cells determines testis size and sperm output, however, molecular mechanisms regulating Sertoli cell proliferation and maturation are not well-understood. Using a Sertoli cell specific loss-of-function approach, here we showed that transcription factor E4F1 played an important role in murine Sertoli cell proliferation. Compared with their littermate control, E4f1 conditional knockout male mice sired a significantly low number of pups. E4f1 deletion resulted in reduced Sertoli cell number and testis size. Further analyses revealed that E4f1 deletion affected Sertoli cell proliferation in the neonatal testis and caused an increase in apoptosis of spermatogenic cells without affecting normal development of spermatogonia, meiotic and post-meiotic germ cells. These findings have shed new light on molecular controlling of spermatogenesis in mice and a similar mechanism likely exists in other animals. Abstract In the mammalian testes, Sertoli cells are the only somatic cells in the seminiferous tubules that provide structural, nutritional and regulatory support for developing spermatogenic cells. Sertoli cells only proliferate during the fetal and neonatal periods and enter a quiescent state after puberty. Functional evidences suggest that the size of Sertoli cell population determines sperm production and fertility. However, factors that direct Sertoli cell proliferation and maturation are not fully understood. Transcription factor E4F1 is a multifunctional protein that serves essential roles in cell fate decisions and because it interacts with pRB, a master regulator of Sertoli cell function, we hypothesized that E4F1 may have a functional role in Sertoli cells. E4f1 mRNA was present in murine testis and immunohistochemical staining confirmed that E4F1 was enriched in mature Sertoli cells. We generated a conditional knockout mouse model using Amh-cre and E4f1flox/flox lines to study E4F1 fucntion in Sertoli cells and the results showed that E4f1 deletion caused a significant reduction in testis size and fertility. Further analyses revealed that meiosis progression and spermiogenesis were normal, however, Sertoli cell proliferation was impaired and germ cell apoptosis was elevated in the testis of E4f1 conditional knockout mice. On the basis of these findings, we concluded that E4F1 was expressed in murine Sertoli cells and served important functions in regulating Sertoli cell proliferation and fertility.
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- 2020
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27. Deletion of FUNDC2 and CMC4 on Chromosome Xq28 Is Sufficient to Cause Hypergonadotropic Hypogonadism in Men
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Xinxian Deng, Richard A Failor, Emily A Malouf, He Fang, Whitney Neufeld-Kaiser, Asha Pathak, Fuki M. Hisama, Angela M Zou, and Yajuan J. Liu
- Subjects
0301 basic medicine ,medicine.medical_specialty ,FUNDC2 ,lcsh:QH426-470 ,Sertoli cell proliferation ,030204 cardiovascular system & hematology ,Biology ,hypergonadotropic hypogonadism ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Hypergonadotropic hypogonadism ,Internal medicine ,Genetics ,medicine ,Gene ,Sertoli cell barrier ,Loss function ,Genetics (clinical) ,Xq28 deletion ,030304 developmental biology ,0303 health sciences ,apoptosis ,Chromosome ,medicine.disease ,Sertoli cell ,Xq28 ,lcsh:Genetics ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Sex steroid ,030220 oncology & carcinogenesis ,CMC4 ,Molecular Medicine - Abstract
BackgroundHypergonadotropic hypogonadism (HH) is characterized by low sex steroid levels and secondarily elevated gonadotropin levels with either congenital or acquired etiology. Genetic factors leading to HH have yet to be fully elucidated.MethodsHere, we report on genome and transcriptome data analyses from a male patient with HH and history of growth delay who has an inherited deletion of chromosome Xq28. Furthermore, expression analyses were done for this patient and his unaffected family members and compared to normal controls to identify dysregulated genes due to this deletion.ResultsOur patient’s Xq28 deletion is 44,806bp and contains only two genes FUNDC2 and CMC4. Expression of both FUNDC2 and CMC4 are completely abolished in the patient. Gene ontology analyses of differentially expressed genes in the patient in comparison to controls show that significantly up-regulated genes in the patient are enriched in Sertoli cell barrier regulation, apoptosis, inflammatory response and gonadotropin-releasing regulation. Indeed, our patient has an elevated FSH level, which regulates Sertoli cell proliferation and spermatogenesis. In his mother and sister, who are heterozygous for this deletion, X-chromosome inactivation is skewed towards the deleted X, suggesting a mechanism to avoid FSH dysregulation.ConclusionCompared to the previously reported men with variable sized Xq28 deletions, our study suggests that loss of function of FUNDC2 and/or CMC4 results in dysregulation of apoptosis, inflammation and FSH, and is sufficient to cause Xq28-associated HH.
- Published
- 2020
28. Wild-type p53-induced phosphatase 1 (WIP1) regulates the proliferation of swine Sertoli cells through P53
- Author
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Mingrui Zhang, Zhiguo Liu, Jingjing Che, Kui Li, Bingyuan Wang, and Yulian Mu
- Subjects
0301 basic medicine ,Male ,endocrine system ,Swine ,Phosphatase ,Sertoli cell proliferation ,Reproductive technology ,Biology ,Gene Expression Regulation, Enzymologic ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,microRNA ,Genetics ,medicine ,Animals ,Phosphorylation ,Molecular Biology ,Cells, Cultured ,Cell Proliferation ,Sertoli Cells ,Cell growth ,Wild type ,Sertoli cell ,Cell biology ,Protein Phosphatase 2C ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Reproductive Medicine ,030220 oncology & carcinogenesis ,Animal Science and Zoology ,Tumor Suppressor Protein p53 ,Spermatogenesis ,Protein Processing, Post-Translational ,Developmental Biology ,Biotechnology - Abstract
Wild-type p53-induced phosphatase 1 (WIP1) plays an oncogenic function by increasing cell proliferation in various cancer types. Deficiency in WIP1 expression leads to male infertility, possibly by impairing the blood–testis barrier and spermatogenesis. However, how WIP1 functions in the Sertoli cells to affect male reproduction remains unclear. Thus, in the present study we used a swine Sertoli cell line to investigate whether WIP1 regulated the proliferation of Sertoli cells to participate in male reproduction. The WIP1 inhibitor GSK2830371, WIP1-short interference (si) RNAs and an upstream microRNA (miR-16) were used to inhibit the expression of WIP1, after which the proliferation of swine Sertoli cells, P53 expression and the levels of P53 phosphorylation were determined. Inhibiting WIP1 expression suppressed swine Sertoli cell proliferation, increased P53 expression and increased levels of P53 phosphorylation. In addition, overexpression of miR-16 in swine Sertoli cells resulted in a decrease in WIP1 expression and increases in both P53 expression and P53 phosphorylation. Together, these findings suggest that WIP1 positively regulates the proliferation of swine Sertoli cells by inhibiting P53 phosphorylation, and the miR-16 is likely also involved by targeting WIP1.
- Published
- 2020
29. Dibutyl phthalate promotes juvenile Sertoli cell proliferation by decreasing the levels of the E3 ubiquitin ligase Pellino 2
- Author
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Xiaodong Han, Tan Ma, Yuan Zhou, Dongmei Li, Jiayin Qiu, Jiang Wu, Yusheng Chen, Jie Ding, and Jiwei Hou
- Subjects
Male ,Dibutyl phthalate ,Ubiquitin-Protein Ligases ,Sertoli cells ,Health, Toxicology and Mutagenesis ,Proliferation ,Phthalic Acids ,Sertoli cell proliferation ,Apoptosis ,010501 environmental sciences ,01 natural sciences ,Andrology ,Mice ,lcsh:RC963-969 ,03 medical and health sciences ,chemistry.chemical_compound ,Downregulation and upregulation ,Plasticizers ,medicine ,Animals ,Cell Proliferation ,030304 developmental biology ,0105 earth and related environmental sciences ,Mice, Inbred BALB C ,0303 health sciences ,biology ,Kinase ,Research ,lcsh:Public aspects of medicine ,Public Health, Environmental and Occupational Health ,Nuclear Proteins ,lcsh:RA1-1270 ,Sertoli cell ,Ubiquitin ligase ,Peli2 ,medicine.anatomical_structure ,chemistry ,Monobutyl phthalate ,Cell culture ,lcsh:Industrial medicine. Industrial hygiene ,biology.protein - Abstract
Background A previous study showed that dibutyl phthalate (DBP) exposure disrupted the growth of testicular Sertoli cells (SCs). In the present study, we aimed to investigate the potential mechanism by which DBP promotes juvenile SC proliferation in vivo and in vitro. Methods Timed pregnant BALB/c mice were exposed to vehicle, or DBP (50, 250, and 500 mg/kg/day) from 12.5 days of gestation until delivery. In vitro, CCK-8 and EdU incorporation assays were performed to determine the effect of monobutyl phthalate (MBP), the active metabolite of DBP, on the proliferation of TM4 cells, which are a juvenile testicular SC cell line. Western blotting analysis, quantitative PCR (q-PCR), and flow cytometry were performed to analyse the expression of genes and proteins related to the proliferation and apoptosis of TM4 cells. Coimmunoprecipitation was used to determine the relationship between the ubiquitination of interleukin 1 receptor-associated kinase 1 (IRAK1) and the effect of MBP on promoting the proliferation of TM4 cells. Results In the 50 mg/kg/day DBP-exposed male mice offspring, the number of SCs was significantly increased. Consistent with the in vivo results, in vitro experiments revealed that 0.1 mM MBP treatment promoted the proliferation of TM4 cells. Furthermore, the data showed that 0.1 mM MBP-mediated downregulation of the E3 ubiquitin ligase Pellino 2 (Peli2) increased ubiquitination of IRAK1 by K63, which activated MAPK/JNK signalling, leading to the proliferation of TM4 cells. Conclusions Prenatal exposure to DBP led to abnormal proliferation of SCs in prepubertal mice by affecting ubiquitination of the key proliferation-related protein IRAK1 via downregulation of Peli2.
- Published
- 2020
30. Vitamin E promotes ovine Sertoli cell proliferation by regulation of genes associated with cell division and the cell cycle
- Author
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Yuefeng Gao, Luyang Jian, Zoltan Machaty, Hailing Luo, and Wei Lu
- Subjects
0301 basic medicine ,Male ,endocrine system ,Cell division ,medicine.medical_treatment ,Sertoli cell proliferation ,Bioengineering ,Biology ,03 medical and health sciences ,medicine ,Animals ,Vitamin E ,Gene ,Cell Proliferation ,Sertoli Cells ,Sheep ,urogenital system ,Cell Cycle ,0402 animal and dairy science ,04 agricultural and veterinary sciences ,Cell cycle ,Sertoli cell ,040201 dairy & animal science ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Animal Science and Zoology ,Cell Division ,Biotechnology - Abstract
The effect of Vitamin E on the proliferation of ovine Sertoli cells was investigated. Sertoli cells were isolated and treated with various amounts of Vitamin E (0 μM, 400 μM, 800 μM, 1000 μM, 1200 μM, 1400 μM and 1600 μM) for 24 h. We found that at the concentration of 1200 μM, Vitamin E promoted Sertoli cell proliferation very effectively. It also increased the proportion of cells in the G1 phase while reduced that in the S and G2/M phases, suggesting that its effect on Sertoli cell proliferation is achieved by enhancing progression through the cell cycle. In addition, Vitamin E significantly up-regulated the transcript level of the PDPN, BMP6, AMPKα, GSK3β, Myc, and CDK6 genes and down-regulated that of PPARγ, Cyclin B1 and CDK4 as determined by qRT-PCR. Western blot analysis revealed that the expression of BMP6 and PDPN was also upregulated at the protein level, in accordance with the results of the qRT-PCR. Taken together, Vitamin E promoted Sertoli cell proliferation by affecting the expression of genes that regulate cell division and the cell cycle; this indicates that it can have a positive effect on sheep reproductive performance.
- Published
- 2020
31. Activin A Determines Steroid Levels and Composition in the Fetal Testis
- Author
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Kate L Loveland, Sarah C Moody, Julia C. Young, Patrick S Western, David J. Handelsman, Elizabeth A. Richards, Kristian Almstrup, Liza O'Donnell, and Penny A. F. Whiley
- Subjects
Male ,0301 basic medicine ,endocrine system ,medicine.medical_specialty ,animal structures ,Somatic cell ,Sertoli cell proliferation ,Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Pregnancy ,Internal medicine ,Lipid droplet ,Testis ,medicine ,Animals ,Gonadal Steroid Hormones ,Testosterone ,Mice, Knockout ,Fetus ,Sex Determination Processes ,Sertoli cell ,Activins ,030104 developmental biology ,medicine.anatomical_structure ,embryonic structures ,Female ,INHBA Gene ,Spermatogenesis ,030217 neurology & neurosurgery - Abstract
Activin A promotes fetal mouse testis development, including driving Sertoli cell proliferation and cord morphogenesis, but its mechanisms of action are undefined. We performed ribonucleic acid sequencing (RNA-seq) on testicular somatic cells from fetal activin A-deficient mice (Inhba KO) and wildtype littermates at embryonic day (E) E13.5 and E15.5. Analysis of whole gonads provided validation, and cultures with a pathway inhibitor discerned acute from chronic effects of altered activin A bioactivity. Activin A deficiency predominantly affects the Sertoli cell transcriptome. New candidate targets include Minar1, Sel1l3, Vnn1, Sfrp4, Masp1, Nell1, Tthy1 and Prss12. Importantly, the testosterone (T) biosynthetic enzymes present in fetal Sertoli cells, Hsd17b1 and Hsd17b3, were identified as activin-responsive. Activin-deficient testes contained elevated androstenedione (A4), displayed an Inhba gene dose-dependent A4/T ratio, and contained 11-keto androgens. The remarkable accumulation of lipid droplets in both Sertoli and germ cells at E15.5 indicated impaired lipid metabolism in the absence of activin A. This demonstrated for the first time that activin A acts on Sertoli cells to determine local steroid production during fetal testis development. These outcomes reveal how compounds that perturb fetal steroidogenesis can function through cell-specific mechanisms and can indicate how altered activin levels in utero may impact testis development.
- Published
- 2020
32. Thyroid hormone actions on male reproductive system of teleost fish
- Author
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Rafael Henrique Nóbrega, Maira da Silva Rodrigues, Hamid R. Habibi, and Aldo Tovo-Neto
- Subjects
Male ,0301 basic medicine ,Thyroid Hormones ,endocrine system ,Sex Differentiation ,medicine.drug_class ,Thyroid Gland ,Morphogenesis ,Sertoli cell proliferation ,03 medical and health sciences ,Endocrinology ,Germ cell proliferation ,Testis ,medicine ,Animals ,Zebrafish ,Sexual differentiation ,biology ,Reproduction ,Fishes ,Sertoli cell ,biology.organism_classification ,Androgen ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Animal Science and Zoology ,Hormone - Abstract
Thyroid hormones (THs) play important roles in the regulation of many biological processes of vertebrates, such as growth, metabolism, morphogenesis and reproduction. An increasing number of studies have been focused on the involvement of THs in the male reproductive system of vertebrates, in particular of fish. Therefore, this mini-review aims to summarize the main findings on THs role in male reproductive system of fish, focusing on sex differentiation, testicular development and spermatogenesis. The existing data in the literature have demonstrated that THs exert their roles at the different levels of the hypothalamic-pituitary-gonadal (HPG) axis. In general a positive correlation has been shown between THs and fish reproductive status; where THs are associated with testicular development, growth and maturation. Recently, the molecular mechanisms underlying the role of THs in spermatogenesis have been unraveled in zebrafish testis. THs promote germ cell proliferation and differentiation by increasing a stimulatory growth factor of spermatogenesis produced by Sertoli cells. In addition, THs enhanced the gonadotropin-induced androgen release in zebrafish testis. Next to their functions in the adult testis, THs are involved in the gonadal sex differentiation through modulating sex-related gene expression, and testicular development via regulation of Sertoli cell proliferation. In conclusion, this mini-review showed that THs modulate the male reproductive system during the different life stages of fish. The physiological and molecular mechanisms showed a link between the thyroid and reproduction, suggesting a possibly co-evolution and interdependence of these two systems.
- Published
- 2018
33. Role of Akt and mammalian target of rapamycin signalling in insulin-like growth factor 1-mediated cell proliferation in porcine Sertoli cells
- Author
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Chinju Johnson, John P. Kastelic, and Jacob C. Thundathil
- Subjects
Male ,endocrine system ,Sus scrofa ,Sertoli cell proliferation ,Gene Expression ,P70-S6 Kinase 1 ,Biology ,Receptor, IGF Type 1 ,Wortmannin ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Testis ,Genetics ,medicine ,Animals ,Insulin-Like Growth Factor I ,Phosphorylation ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cells, Cultured ,030304 developmental biology ,Cell Proliferation ,0303 health sciences ,Sertoli Cells ,Cell growth ,TOR Serine-Threonine Kinases ,Ribosomal Protein S6 Kinases, 70-kDa ,Sertoli cell ,Cell biology ,medicine.anatomical_structure ,Cholesterol ,Reproductive Medicine ,chemistry ,030220 oncology & carcinogenesis ,Ribosomal protein s6 ,Models, Animal ,Animal Science and Zoology ,Proto-Oncogene Proteins c-akt ,Developmental Biology ,Biotechnology ,Signal Transduction - Abstract
The critical role of insulin-like growth factor (IGF) 1 in promoting Sertoli cell proliferation invivo and invitro has been established, but its downstream signalling mechanisms remain unknown. In addition to mitogenic effects, a role for IGF1 in mediating cholesterol biosynthesis within testes has been implied. The aims of this study were to investigate the roles of: (1) phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) signalling in IGF1-mediated Sertoli cell proliferation; and (2) IGF1 in mediating cholesterol biosynthesis in Sertoli cells. Primary cultures of Sertoli cells were prepared from 1-week-old porcine testes. On Day 3 of culture, Sertoli cells were treated with 300ng mL−1 IGF1, alone or in combination with inhibitors of IGF1 receptor (2μM picropodophyllotoxin), Akt (1μM wortmannin) or mTOR (200nM rapamycin). Cells were cultured for 30min and phosphorylation levels of Akt, mTOR and p70 ribosomal protein S6 kinase (p70S6K) were determined by immunoblotting. Cell proliferation and quantitative polymerase chain reaction assays were conducted using cells cultured for 24h. IGF1 increased phosphorylation of Akt, mTOR and p70S6K and cell proliferation, and these effects were inhibited by inhibitors of IGF1R, Akt and mTOR. Furthermore, IGF1 upregulated the expression of cholesterol biosynthetic genes (3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS1) and cytochrome P450, family 5, subfamily A, polypeptide 1 (CYP5A1)), but not sterol regulatory element-binding transcription factor 1 (SREBF1). Increased phosphorylation of p70S6K, a major downstream target of mTOR, and upregulated expression of genes involved in cholesterol biosynthesis are indicative of the key role played by IGF1 in regulating the synthesis of cholesterol, the precursor for steroid hormones.
- Published
- 2019
34. Metformin counteracts the effects of FSH on rat Sertoli cell proliferation
- Author
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Agostina Gorga, Mariana Regueira, Gustavo Marcelo Rindone, Maria Noel Lujan Galardo, Silvina Beatriz Meroni, Eliana Herminia Pellizzari, Maria Fernanda Riera, and Selva B. Cigorraga
- Subjects
Male ,0301 basic medicine ,endocrine system ,Embryology ,medicine.medical_specialty ,CIENCIAS MÉDICAS Y DE LA SALUD ,Primary Cell Culture ,Proliferation ,Sertoli cell proliferation ,Rats, Sprague-Dawley ,03 medical and health sciences ,Follicle-stimulating hormone ,p21cip1 ,0302 clinical medicine ,Endocrinology ,Cyclin D1 ,Internal medicine ,FSH ,medicine ,Animals ,Hypoglycemic Agents ,Sertoli Cell ,Cell Proliferation ,Sertoli Cells ,Cell growth ,Chemistry ,Ribosomal Protein S6 Kinases, 70-kDa ,Obstetrics and Gynecology ,Cell Biology ,Sertoli cell ,Metformin ,Otras Ciencias Médicas ,030104 developmental biology ,medicine.anatomical_structure ,Reproductive Medicine ,Cell culture ,030220 oncology & carcinogenesis ,Follicle Stimulating Hormone ,Acetyl-CoA Carboxylase ,Hormone ,medicine.drug - Abstract
Metformin (MET) is one of the most widely used anti-hyperglycemic agents for treating patients with type 2 diabetes and it has started to be used in pediatric population at ages when Sertoli cells are still proliferating. It is well known that follicle-stimulating hormone (FSH) is the major Sertoli cell mitogen. The aim of the study is to investigate a possible effect of MET, which has been shown to have anti-proliferative properties, on FSH regulation of postnatal Sertoli cell proliferation and on the molecular mechanisms involved in this regulation. The present study was performed in eight-day-old rat Sertoli cell cultures. The results obtained show that MET in the presence of FSH increases phosphorylated acetyl-CoA carboxylase and decreases phosphorylated p70S6K levels. Moreover, we show that MET decreases FSH-stimulated Sertoli cell proliferation, and this decrease is accompanied by a reduction in FSH-stimulated Ccnd1 and Ccnd2 expression and an increase in cell cycle inhibitor p21Cip expression. Altogether, these results suggest that MET can, at least in part, counteract the effect of FSH on postnatal Sertoli cell proliferation. Fil: Rindone, Gustavo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Gorga, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Regueira, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Pellizzari, Eliana Herminia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Cigorraga, Selva Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Galardo, Maria Noel Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Meroni, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Riera, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
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- 2018
35. miR-375 down-regulation of the rearranged L-myc fusion and hypoxia-induced gene domain protein 1A genes and effects on Sertoli cell proliferation
- Author
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Xin Liu, Jia Guo, Boxing Sun, Chunyan Bai, Yuwei Yang, Zhihui Zhao, and Mengdi Liang
- Subjects
0301 basic medicine ,POU domain ,Cell growth ,RLF ,lcsh:Animal biochemistry ,Sertoli cell proliferation ,Transfection ,Biology ,Animal Breeding and Genetics ,HIGD1A ,Molecular biology ,Article ,miR-375 ,03 medical and health sciences ,030104 developmental biology ,Real-time polymerase chain reaction ,Mir-375 ,Gene expression ,Animal Science and Zoology ,lcsh:Animal culture ,lcsh:QP501-801 ,Gene ,Cell Proliferation ,lcsh:SF1-1100 ,Food Science - Abstract
Objective This study aimed to screen and identify the target genes of miR-375 in pig Sertoli (ST) cells and to elucidate the effect of miR-375 on the proliferation of ST cells. Methods In this study, bioinformatics software was used to predict and verify miR-375 target genes. Quantitative polymerase chain reaction (PCR) was used to detect the relationship between miR-375 and its target genes in ST cells. Enzyme-linked immunosorbent assay (ELISA) of rearranged L-myc fusion (RLF) and hypoxia-induced gene domain protein 1A (HIGD1A) was performed on porcine ST cells, which were transfected with a miR-375 mimics and inhibitor to verify the results. Dual luciferase reporter gene assays were performed to assess the interactions among miR-375, RLF, and HIGD1A. The effect of miR-375 on the proliferation of ST cells was analyzed by CellTiter 96 AQueous One Solution Cell Proliferation Assay (MTS). Results Five possible target genes of miR-375, including RLF, HIGD1A, colorectal cancer associated 2, POU class 3 homeobox 1, and WW domain binding protein 1 like, were found. The results of quantitative PCR suggested that mRNA expression of RLF and HIGD1A had a negative correlation with miR-375, indicating that RLF and HIGD1A are likely the target genes of miR-375. The ELISA results revealed that RLF and HIGD1A were negatively correlated with the miR-375 protein level. The luminescence results for the miR-375 group co-transfected with wild-type RLF and HIGD1A vector were significantly lower than those of the miR-375 group co-transfected with the blank vector or mutant RLF and HIGD1A vectors. The present findings suggest that RLF and HIGD1A are target genes of miR-375 and that miR-375 inhibits ST cell proliferation according to MTS analysis. Conclusion It was speculated that miR-375 affects cell proliferation through its target genes, which play an important role in the development of testicular tissue.
- Published
- 2018
36. Dysregulation of FGFR signalling by a selective inhibitor reduces germ cell survival in human fetal gonads of both sexes and alters the somatic niche in fetal testes
- Author
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Signe Perlman, K. Harpelunde Poulsen, Rod T. Mitchell, John E Nielsen, Lene Lundvall, E. Rajpert-De Meyts, K Juul Hare, Hanne Frederiksen, A. Jørgensen, Cecilie Melau, L Langhoff Thuesen, and Anders Juul
- Subjects
Fibroblast Growth Factor 9 ,Male ,endocrine system ,Somatic cell ,Cell Survival ,human fetal testis / human fetal ovary / ex vivo culture / FGF9 signalling / gonocytes / oogonia / gonadal sex differentiation / initiation of meiosis / somatic niche formation ,Sertoli cell proliferation ,Ovary ,Biology ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Gonocyte ,FGF9 ,Pregnancy ,Wnt4 Protein ,WNT4 ,Testis ,medicine ,Humans ,Cell Lineage ,Pyrroles ,Receptor, Fibroblast Growth Factor, Type 1 ,030304 developmental biology ,Cell Proliferation ,0303 health sciences ,Reproductive Biology ,030219 obstetrics & reproductive medicine ,Sertoli Cells ,Rehabilitation ,Obstetrics and Gynecology ,Gene Expression Regulation, Developmental ,Leydig Cells ,Cell Differentiation ,Sertoli cell ,Pregnancy Trimester, First ,medicine.anatomical_structure ,Germ Cells ,Reproductive Medicine ,Original Article ,Female ,Germ cell ,Signal Transduction - Abstract
STUDY QUESTION Does experimental manipulation of fibroblast growth factor 9 (FGF9)-signalling in human fetal gonads alter sex-specific gonadal differentiation? SUMMARY ANSWER Inhibition of FGFR signalling following SU5402 treatment impaired germ cell survival in both sexes and severely altered the developing somatic niche in testes, while stimulation of FGF9 signalling promoted Sertoli cell proliferation in testes and inhibited meiotic entry of germ cells in ovaries. WHAT IS KNOWN ALREADY Sex-specific differentiation of bipotential gonads involves a complex signalling cascade that includes a combination of factors promoting either testicular or ovarian differentiation and inhibition of the opposing pathway. In mice, FGF9/FGFR2 signalling has been shown to promote testicular differentiation and antagonize the female developmental pathway through inhibition of WNT4. STUDY DESIGN, SIZE, DURATION FGF signalling was manipulated in human fetal gonads in an established ex vivo culture model by treatments with recombinant FGF9 (25 ng/ml) and the tyrosine kinase inhibitor SU5402 (10 μM) that was used to inhibit FGFR signalling. Human fetal testis and ovary tissues were cultured for 14 days and effects on gonadal development and expression of cell lineage markers were determined. PARTICIPANTS/MATERIALS, SETTING, METHODS Gonadal tissues from 44 male and 33 female embryos/fetuses from first trimester were used for ex vivo culture experiments. Tissues were analyzed by evaluation of histology and immunohistochemical analysis of markers for germ cells, somatic cells, proliferation and apoptosis. Culture media were collected throughout the experimental period and production of steroid hormone metabolites was analyzed in media from fetal testis cultures by liquid chromatography–tandem mass spectrometry (LC-MS/MS). MAIN RESULTS AND THE ROLE OF CHANCE Treatment with SU5402 resulted in near complete loss of gonocytes (224 vs. 14 OCT4+ cells per mm2, P LARGE SCALE DATA N/A LIMITATIONS, REASONS FOR CAUTION Ex vivo culture may not replicate all aspects of fetal gonadal development and function in vivo. Although the effects of FGF9 were studied in ex vivo culture experiments, there is no direct evidence that FGF9 acts in vivo during human fetal gonadogenesis. The FGFR inhibitor (SU5402) used in this study is not specific to FGFR2 but inhibits all FGF receptors and off-target effects on unrelated tyrosine kinases should be considered. WIDER IMPLICATIONS OF THE FINDINGS The findings of this study suggest that dysregulation of FGFR-mediated signalling may affect both testicular and ovarian development, in particular impacting the fetal germ cell populations in both sexes. STUDY FUNDING/COMPETING INTEREST(S) This work was supported in part by an ESPE Research Fellowship, sponsored by Novo Nordisk A/S to A.JØ. Additional funding was obtained from the Erichsen Family Fund (A.JØ.), the Aase and Ejnar Danielsens Fund (A.JØ.), the Danish Government’s support for the EDMaRC programme (A.JU.) and a Wellcome Trust Intermediate Clinical Fellowship (R.T.M., Grant no. 098522). The Medical Research Council (MRC) Centre for Reproductive Health (R.T.M.) is supported by an MRC Centre Grant (MR/N022556/1). The authors have no conflict of interest to disclose.
- Published
- 2019
37. DDB1 Regulates Sertoli Cell Proliferation and Testis Cord Remodeling by TGFβ Pathway
- Author
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Wei Zheng, Xiaohua Jiang, Jabeen Nazish, Qinghua Shi, Ranjha Khan, and Fazal Wahab
- Subjects
0301 basic medicine ,Male ,Cell signaling ,endocrine system ,Morphogenesis ,Sertoli cell proliferation ,Ddb1 ,Article ,03 medical and health sciences ,TGFβ ,Mice ,0302 clinical medicine ,Transforming Growth Factor beta ,Genetics ,medicine ,Animals ,Genetics (clinical) ,Cell Proliferation ,Spermatic Cord ,Sertoli Cells ,biology ,urogenital system ,Transforming growth factor beta ,Sertoli cell ,Embryonic stem cell ,testis cord ,spermatogenesis ,Cell biology ,DNA-Binding Proteins ,030104 developmental biology ,medicine.anatomical_structure ,Animals, Newborn ,biology.protein ,Spermatogenesis ,030217 neurology & neurosurgery ,Intracellular ,Gene Deletion ,Signal Transduction - Abstract
Testis cords are the embryonic precursors of the seminiferous tubules. Development of testis cords is a key event during embryonic testicular morphogenesis and is regulated by multiple signaling molecules produced by Sertoli cells. However, the exact nature and the cascade of molecular events underlying testis cord development remain to be uncovered. In the current study, we explored the role of DNA damage binding protein 1 (DDB1) in Sertoli cells during mouse testis cord development. The genetic ablation of Ddb1 specifically in Sertoli cells resulted in the compromised Sertoli cell proliferation and disruption of testis cord remodeling in neonatal mice. This testicular dysgenesis persisted through adulthood, resulting in smaller testis and low sperm production. Mechanistically, we observed that the DDB1 degradation can stabilize SET domain-containing lysine methyltransferase 8 (SET8), which subsequently decreases the phosphorylation of SMAD2, an essential intracellular component of transforming growth factor beta (TGF&beta, ) signaling. Taken together, our results suggest an essential role of Ddb1 in Sertoli cell proliferation and normal remodeling of testis cords via TGF&beta, pathway. To our knowledge, this is the first upstream regulators of TGF&beta, pathway in Sertoli cells, and therefore it furthers our understanding of testis cord development.
- Published
- 2019
38. Vgll3 and the Hippo pathway are regulated in Sertoli cells upon entry and during puberty in Atlantic salmon testis
- Author
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Kjærner-Semb, Erik, Ayllon, Fernando, Kleppe, Lene, Sørhus, Elin, Skaftnesmo, Kai, Furmanek, Tomasz, Segafredo, Frida T, Thorsen, Anders, Fjelldal, Per Gunnar, Hansen, Tom, Taranger, Geir Lasse, Andersson, Eva, Schulz, Rüdiger W, Wargelius, Anna, Edvardsen, Rolf B, Sub Developmental Biology, Developmental Biology, Sub Developmental Biology, and Developmental Biology
- Subjects
0301 basic medicine ,Male ,Cell type ,endocrine system ,Sex Differentiation ,Somatic cell ,Salmo salar ,Sertoli cell proliferation ,Gene Expression ,lcsh:Medicine ,Biology ,Protein Serine-Threonine Kinases ,Article ,Andrology ,03 medical and health sciences ,Gene expression ,Testis ,medicine ,Animals ,Sexual Maturation ,Salmo ,lcsh:Science ,Cell Proliferation ,Hippo signaling pathway ,Multidisciplinary ,Granulosa Cells ,Sertoli Cells ,lcsh:R ,Proliferation activity ,biology.organism_classification ,Sertoli cell ,030104 developmental biology ,medicine.anatomical_structure ,Germ Cells ,Female ,lcsh:Q ,Transcription Factors - Abstract
Vgll3 is linked to age at maturity in Atlantic salmon (Salmo salar). However, the molecular mechanisms involving Vgll3 in controlling timing of puberty as well as relevant tissue and cell types are currently unknown. Vgll3 and the associated Hippo pathway has been linked to reduced proliferation activity in different tissues. Analysis of gene expression reveals for the first time that vgll3 and several members of the Hippo pathway were down-regulated in salmon testis during onset of puberty and remained repressed in maturing testis. In the gonads, we found expression in Sertoli and granulosa cells in males and females, respectively. We hypothesize that vgll3 negatively regulates Sertoli cell proliferation in testis and therefore acts as an inhibitor of pubertal testis growth. Gonadal expression of vgll3 is located to somatic cells that are in direct contact with germ cells in both sexes, however our results indicate sex-biased regulation of vgll3 during puberty.
- Published
- 2018
39. Impact of a timed-release FSH treatment from 2 to 6 months of age in bulls I: Endocrine and testicular development of beef bulls
- Author
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A.D. Rodrigues, Michael L. Day, C. Premanandan, F. M. Abreu, J. M. DeJarnette, L. H. Cruppe, and B.R. Harstine
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Male ,0301 basic medicine ,endocrine system ,medicine.medical_specialty ,Sertoli cell proliferation ,Biology ,Weight Gain ,Andrology ,03 medical and health sciences ,Follicle-stimulating hormone ,Food Animals ,Internal medicine ,Testis ,medicine ,Animals ,Testosterone ,Sexual Maturation ,Spermatogenesis ,Small Animals ,Equine ,0402 animal and dairy science ,04 agricultural and veterinary sciences ,Sertoli cell ,040201 dairy & animal science ,Activins ,030104 developmental biology ,Seminiferous tubule ,medicine.anatomical_structure ,Tubule ,Endocrinology ,Delayed-Action Preparations ,Scrotum ,Cattle ,Animal Science and Zoology ,Follicle Stimulating Hormone ,hormones, hormone substitutes, and hormone antagonists ,Blood sampling - Abstract
In prepubertal males, FSH facilitates Sertoli cell proliferation and testis maturation. The study aimed to determine the effect of an exogenous FSH treatment on hormone secretion and testis development in Angus bulls. Bulls (n = 22) weaned at 53 ± 3.8 days of age were randomized into two treatment groups based on age and pedigree. Beginning at Day 59, bulls were injected im every 3.5 days with either 30 mg FSH (Folltropin-V; NIH-FSH-P1 units) in a 2% hyaluronan solution (FSH-HA, n = 11) or saline (control, n = 11) until Day 167.5. Blood samples to assess FSH, activin A, and testosterone were collected prior to each treatment. To determine how FSH profiles surrounding treatment were affected, three intensive blood sampling periods, each encompassing two treatment administrations, began at Day 66, 108, and 157, and blood was collected at 0, 6, 12, 18, 24, 36, 60, and 84 h respective to time of treatment. Scrotal circumference (SC) and BW were measured monthly. Bulls were castrated at Day 170 to measure testis size, seminiferous tubule diameter, and the number of Sertoli and germ cells per tubule cross-section. During intensive FSH sampling, FSH-HA bulls experienced an increase (P 0.05) in FSH over control bulls for at least 18 h post-injection in all instances. In blood collected every 3.5 days, FSH concentrations in FSH-HA bulls were increased (P 0.05) over initial Day 59 concentration from Day 97.5-167.5. FSH concentrations did not differ between treatments from Day 59-90.5, but were greater (P 0.05) in FSH-HA from Day 94-167.5. Concentrations of activin A assessed for Day 59, 83.5, 94, 129, and 167.5 were greater (P 0.05) in FSH-HA than control bulls on Day 83.5 and 94. The treatments did not differ (P 0.1) in testosterone, BW, SC, testis size, tubule diameter, or number of germ cells per tubule. However, the number of Sertoli cells per tubule was greater in FSH-HA than control bulls (45.2 ± 1.4 vs. 41.6 ± 0.9 cells, P 0.05). In summary, FSH-HA treatment every 3.5 days from Day 59-167.5 maintained elevated FSH for a minimum of 18 h post-injection, likely attributable to the addition of HA. We propose the exogenous FSH-HA treatment initiates a positive feedback loop that includes an increased density of Sertoli cells per tubule cross-section, which is related to increased activin A concentrations on Day 83.5 and 94. Furthermore, this activin A increase preceded an increase in endogenous FSH from Day 94-167.5 in FSH-HA bulls.
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- 2018
40. Identification of a Critical Window for Ganciclovir-Induced Disruption of Testicular Development in Rats
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Valdemiro Amaro da Silva Junior, Anderson J.M. Andrade, Davyson de Lima Moreira, Dária Louise Barbosa Machado, Amanda Caroline Venturelli, Rafaela Adams Philipsen, Diogo Henrique Kita, Taiza Stumpp, Isabelle Hernandez Cantão, Rosana Nogueira de Morais, Alluanan Adelson do Nascimento Silva, and Katlyn Barp Meyer
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Male ,0301 basic medicine ,Delayed puberty ,endocrine system ,Time Factors ,Somatic cell ,medicine.drug_class ,Organogenesis ,viruses ,Sertoli cell proliferation ,Gestational Age ,Biology ,Toxicology ,Antiviral Agents ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Gonocyte ,Pregnancy ,Testis ,medicine ,Animals ,Sexual Maturation ,Rats, Wistar ,Ganciclovir ,Cell Proliferation ,Fetus ,030219 obstetrics & reproductive medicine ,Sertoli cell ,Androgen ,Rats ,Germ Cells ,030104 developmental biology ,medicine.anatomical_structure ,In utero ,Prenatal Exposure Delayed Effects ,Female ,medicine.symptom - Abstract
Ganciclovir (GCV) has been implicated in the development of testicular alterations. Exposure on gestational day (GD) 10 in rats induced permanent effects, including focal reduction or absence of germ cells (Sertoli cell-only tubules). Because the timing of exposure can be critical for testicular effects, we exposed rat dams to 300 mg/kg GCV (3 100 mg/kg subcutaneous injections) on GD10, 14 and 19, when germ cells have high rates of migration, proliferation and are mitotically quiescent, respectively. Males exposed to GCV in utero on GD10 and 14 were evaluated for androgenization markers, serum and fecal androgens, and testicular histomorphometry at adulthood. Double-labeling immunofluorescence for DAZL and Ki67 were used to assess gonocytes number and the proliferative activity of germ and somatic cells in fetal testes on GD15 and 20, ie, 24 h after GCV exposure. Adult rats exposed on GD14 showed delayed puberty onset, despite normal androgen levels. Also, there was a 50% reduction in testicular weight and about 30% of seminiferous tubules lacking germ cells. Effects on GD10 animals were less pronounced. In the fetal testis, the number of gonocytes was reduced by 50% in rats exposed on GD14, but normal in GD19 fetuses. GCV also reduced Sertoli cell proliferation immunolabeling in GD19 fetuses and Sertoli cell number in adults. In conclusion, GCV toxicity on germ cells seems to be linked to their proliferation rate and GD14 is a critical window in rats, when GCV exposure causes an acute massive loss of germ cells that persists until adulthood.
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- 2017
41. Sertoli cell proliferation in the adult testis is induced by unilateral gonadectomy in African catfish
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Schulz, Rüdiger W., van Dijk, Wytske, Chaves-Pozo, Elena, García-López, Ángel, de França, Luiz R., and Bogerd, Jan
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CATFISHES , *LUTEINIZING hormone , *SOMATOSTATIN , *PITUITARY extract , *CASTRATION , *SERTOLI cells , *GERM cells , *TESTIS physiology , *PHYSIOLOGY - Abstract
Abstract: Survival and development of male germ cells depends on their close contact with Sertoli cells. In the cystic spermatogenesis found in fish, one germ cell clone, initially a single undifferentiated spermatogonium type A, is enclosed by and accompanied through spermatogenesis by a group of Sertoli cells. Previous work showed that after forming such spermatogenic cysts, Sertoli cells proliferated mainly during the mitotic expansion of the spermatogonial clone in the cyst. Here, we used unilateral gonadectomy (ULG) as experimental model to study Sertoli cell proliferation at the start of cyst development in adult African catfish testis. Four days after surgery, we observed a particularly strong increase in the number of mitotic Sertoli cells along with a significant increase in the number of mitotic single type A spermatogonia. Proliferation of pairs of spermatogonia or of larger germ cell clones, however, did not change. At the same time, pituitary transcript levels of the three gonadotropin-subunits (cga, glycoprotein hormones, alpha polypeptide; fshb, follicle stimulating hormone, beta polypeptide; lhb, luteinizing hormone, beta polypeptide) were not different between sham-operated and ULG males. However, expression of the gonadotropin-releasing hormone receptor gene gnrhr1 was significantly reduced after ULG, and Lh plasma levels were slightly elevated. In the testis remaining after ULG, Fsh receptor (fshr) mRNA levels increased significantly but luteinizing hormone/choriogonadotropin receptor (lhcgr) mRNA levels did not change. Circulating androgen levels did not differ between groups, but testicular androgen release increased significantly 2- to 3-fold after ULG. Considering the strong steroidogenic potency of Fsh and the expression of the fshr gene by Leydig cells in catfish, we explain the absence of an effect of ULG on circulating androgen levels by an Fshr-mediated, compensatory increase in the steroid production of the remaining testis, perhaps supported in addition by the increased Lh plasma levels. Since Fsh is a major stimulator of mammalian Sertoli cell proliferation, we propose that ULG-induced activation of the Fsh signalling system also promoted Sertoli cell proliferation and – possibly as a consequence of that – proliferation of single type A spermatogonia, providing the basis for an increased spermatogenic capacity. [Copyright &y& Elsevier]
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- 2012
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42. Sertoli cells proliferate in adult rats with prenatal exposure to 3,3′,4,4′,5-pentachlorobiphenyl.
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Wakui, Shin, Muto, Tomoko, Suzuki, Yoshihiko, Takahashi, Hiroyuki, and Hano, Hiroshi
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SERTOLI cells , *LABORATORY rats , *SPERMATOGENESIS in animals , *SPRAGUE Dawley rats , *LUTEINIZING hormone , *TESTOSTERONE , *TESTICULAR diseases - Abstract
Sertoli cells play a critical role in spermatogenesis, and in adults, they are terminally differentiated with loss of proliferative activity. This study revealed Sertoli cell proliferation in 17-week-old Sprague-Dawley rats whose dams had been intragastrically administered 250 ng of 3,3′,4,4′,5-pentachlorobiphenyl/kg on days 13-19 postconception. Immunohistochemical evidence of proliferating cell nuclear antigen (PCNA) expression and electron microscope observation of mitotic figures confirmed the proliferation. Because the serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone concentrations were similar to those of vehicle-treated rats, a direct endocrine cause for the observed effects was unlikely. [ABSTRACT FROM AUTHOR]
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- 2012
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43. Role of Connexin 43 in Sertoli Cells of Testis.
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SRIDHARAN, SANTHI, BREHM, RALPH, BERGMANN, MARTIN, and COOKE, PAUL S.
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CONNEXINS , *SERTOLI cells , *TESTIS , *GAP junctions (Cell biology) , *EPITHELIAL cells , *SPERMATOGENESIS , *CELL proliferation , *GENETICS , *CELL growth - Abstract
Connexin 43 (CX43, also known as GJA1) is the predominant testicular gap-junction protein. In the seminiferous epithelium, gap junctions occur between adjacent Sertoli cells and between Sertoli and germ cells. The specific role of CX43 in Sertoli cell has been difficult to study because of the neonatal lethality of the Cx43 global knockout. Recently two laboratories have independently developed a Sertoli cell conditional Cx43 knockout using Cre-loxP methodology. These have allowed the role of CX43 in Sertoli cells to be determined while circumventing lethal abnormalities in organs such as the heart seen in Cx43 global knockouts. In this review the focus is on the insights into the role of CX43 in Sertoli cells derived from these new model systems. Results indicate that CX43 is essential for cessation of proliferation and normal maturation in Sertoli cells. In addition, CX43 in Sertoli cells is required for spermatogenesis, but not early germ cell proliferation. These model systems show that CX43 is important in Sertoli cell development, and will be useful in further studies of its role in Sertoli cell and testis biology. [ABSTRACT FROM AUTHOR]
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- 2007
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44. Impact of a timed-release follicle-stimulating hormone treatment from one to three months of age on endocrine and testicular development of prepubertal bulls1
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A. P. Lemes, R. S. Cipriano, F. M. Abreu, L. H. Cruppe, J. M. DeJarnette, C. Premanandan, B.R. Harstine, Michael L. Day, and M. D. Utt
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endocrine system ,medicine.medical_specialty ,Sertoli cell proliferation ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,Follicle-stimulating hormone ,0302 clinical medicine ,Internal medicine ,Genetics ,medicine ,Endocrine system ,Testosterone ,030219 obstetrics & reproductive medicine ,urogenital system ,0402 animal and dairy science ,04 agricultural and veterinary sciences ,General Medicine ,Sertoli cell ,040201 dairy & animal science ,Endocrinology ,Castration ,medicine.anatomical_structure ,chemistry ,Animal Science and Zoology ,Intramuscular injection ,hormones, hormone substitutes, and hormone antagonists ,Food Science ,Hormone - Abstract
In prepubertal bulls, FSH facilitates testis maturation and a transient proliferation of Sertoli cells. Two experiments examined the effects of exogenous FSH on hormone secretion and testis development in Angus bulls. Exogenous FSH treatment consisted of an intramuscular injection (i.m.) of 30 mg FSH (Folltropin-V) in a 2% hyaluronic acid solution (FSH-HA). In Exp. 1, bulls (50 ± 6.5 d of age) received either FSH-HA ( = 5) or saline (control; = 5) on d 50 and 53.5. Blood samples were collected via jugular venipuncture to assess FSH concentrations every 6 h for 24 h after treatment and every 12 h until 84 h. After each treatment, peripheral FSH concentrations were greater ( 0.1) in BW, SC, testis weight, testis volume, percent of parenchyma composed of tubules, tubule diameter, and concentration of testosterone. The number of Sertoli cells per tubule cross section was greater in the FSH-HA-treated bulls than in the control bulls (33.35 ± 0.9 vs. 28.27 ± 0.9 cells; ˂ 0.05). In summary, the FSH-HA treatment from 35 to 91 d of age resulted in increased endogenous FSH from 70 to 91 d and increased numbers of Sertoli cells at 93 d of age. Exogenous FSH altered endocrine mechanisms regulating endogenous FSH secretion and augmented Sertoli cell proliferation in young bulls, but this effect was apparently not caused by increased activin A concentration in the FSH-HA-treated bulls.
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- 2017
45. Development, function and fate of fetal Leydig cells
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C. Yan Cheng, Qing Wen, and Yi-Xun Liu
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Male ,0301 basic medicine ,endocrine system ,medicine.medical_specialty ,Sertoli cell proliferation ,Biology ,Models, Biological ,Article ,03 medical and health sciences ,Fetus ,Internal medicine ,medicine ,Animals ,Humans ,Cell Lineage ,Androstenedione ,Progenitor cell ,Testosterone ,Progenitor ,Leydig Cells ,Cell Differentiation ,Cell Biology ,Sertoli cell ,Cell biology ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Spermatogenesis ,Developmental Biology - Abstract
During fetal testis development, fetal Leydig cells (FLCs) are found to be originated from multiple progenitor cells. FLC specification and function are under tight regulation of specific genes and signaling proteins. Furthermore, Sertoli cells play a crucial role to regulate FLC differentiation during fetal testis development. FLC progenitor- and FLC-produced biomolecules are also involved in the differentiation and activity of rodent FLCs. The main function of FLCs is to produce androgens to masculinize XY embryos. However, FLCs are capable of producing androstenedione but not testosterone due to the lack of 17β-HSD (17β-hydroxysteroid dehydrogenase), but fetal Sertoli cells express 17β-HSD which thus transforms androstenedione to testosterone in the fetal testis. On the other hand, FLCs produce activin A to regulate Sertoli cell proliferation, and Sertoli cells in turn modulate testis cord expansion. It is now generally accepted that adult Leydig cells (ALCs) gradually replace FLCs during postnatal development to produce testosterone to support spermatogenesis as FLCs undergo degeneration in neonatal and pre-pubertal testes. However, based on studies using genetic tracing mouse models, FLCs are found to persist in adult testes, making up ~20% of total Leydig cells. In this review, we evaluate the latest findings regarding the development, function and fate of FLCs during fetal and adult testis development.
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- 2016
46. Assessment of Sertoli Cell Proliferation by 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide and Sulforhodamine B Assays
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Marco G. Alves, Pedro Oliveira, and Ana Martins
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Male ,0301 basic medicine ,Cell Survival ,Sulforhodamine B ,Tetrazolium Salts ,Sertoli cell proliferation ,Toxicology ,Andrology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,In vivo ,medicine ,Animals ,MTT assay ,Cell Proliferation ,Sertoli Cells ,Rhodamines ,Cell growth ,Chemistry ,Sertoli cell ,Thiazoles ,030104 developmental biology ,medicine.anatomical_structure ,Drug Screening Assays, Antitumor ,Spermatogenesis ,030215 immunology ,Hormone - Abstract
The correct functioning of Sertoli cells (SCs) is pivotal for successful spermatogenesis. They are major targets for hormones, endocrine disruptors, and other substances that men are subjected to every day. One of the main SC functions that quickly responds to a deleterious stimulus is proliferation. This is directly related to the in vivo capacity of these cells to sustain a good number of developing germ cells. The protocols in this article can be tested on SCs of different origin. For the case of human SCs from small human testicular biopsies, a short and simple protocol to isolate and culture these cells is provided. The other protocols discussed herein represent two different procedures, somewhat complementary, to assess SC proliferation. In brief, the sulforhodamine B assay allows the investigator to dye healthy fixed SCs maintained in culture. In the MTT assay, on the other hand, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) is reduced by live SCs. These methods are mostly used to evaluate how SC proliferative activity responds to exposure to compounds such as toxicants or hormones. © 2019 by John Wiley & Sons, Inc.
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- 2019
47. miR-499 promotes immature porcine Sertoli cell growth through the PI3K/AKT pathway by targeting the PTEN gene
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Xiangwei Tang, Anqi Yang, Hui Luo, Bin Chen, Bo Weng, Hu Gao, Maoliang Ran, and Yao Chen
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0301 basic medicine ,endocrine system ,Embryology ,Gene knockdown ,030219 obstetrics & reproductive medicine ,biology ,Akt/PKB signaling pathway ,Cell growth ,Chemistry ,Obstetrics and Gynecology ,Sertoli cell proliferation ,Cell Biology ,Sertoli cell ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,medicine.anatomical_structure ,Reproductive Medicine ,Apoptosis ,biology.protein ,medicine ,PTEN ,PI3K/AKT/mTOR pathway - Abstract
Sertoli cells are indispensable for normal spermatogenesis, and increasing evidence has shown that miRNAs participate in the regulation of Sertoli cell growth. However, the functions and regulatory mechanisms of miRNAs in Sertoli cells of domestic animals have not been fully investigated. In the present study, we mainly investigated the regulatory roles of miR-499 in immature porcine Sertoli cells. The results showed that miR-499 was mainly located in the basement section of seminiferous tubules of prepubertal porcine testicular tissue. Overexpression of miR-499 promoted cell proliferation and inhibited apoptosis, whereas miR-499 inhibition resulted in the opposite effect. The PTEN gene was directly targeted by miR-499, and the expression of mRNA and protein was also negatively regulated by miR-499 in immature porcine Sertoli cells. siRNA-induced PTEN knockdown resulted in a similar effect as an overexpression of miR-499 and abolished the effects of miR-499 inhibition on immature porcine Sertoli cells. Moreover, both miR-499 overexpression and the PTEN knockdown activated the PI3K/AKT signaling pathway, whereas inhibition of the PI3K/AKT signaling pathway caused immature porcine Sertoli cell apoptosis and inhibited cell proliferation. Overall, miR-499 promotes proliferation and inhibits apoptosis in immature porcine Sertoli cells through the PI3K/AKT pathway by targeting the PTEN gene. This study provides novel insights into the effects of miR-499 in spermatogenesis through the regulation of immature Sertoli cell proliferation and apoptosis.
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- 2019
48. Molecular Mechanisms and Signaling Pathways Involved in Sertoli Cell Proliferation
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Selva B. Cigorraga, Gustavo Marcelo Rindone, Maria Fernanda Riera, Silvina Beatriz Meroni, Agostina Gorga, and Maria Noel Lujan Galardo
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0301 basic medicine ,endocrine system ,Somatic cell ,Sertoli cells ,proliferation ,Endocrinology, Diabetes and Metabolism ,Cell ,purl.org/becyt/ford/3.5 [https] ,Sertoli cell proliferation ,030209 endocrinology & metabolism ,Review ,Biology ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,MATURATION ,03 medical and health sciences ,Endocrinology ,0302 clinical medicine ,XENOBIOTICS ,medicine ,xenobiotics ,Protein kinase B ,PI3K/AKT/mTOR pathway ,SERTOLI CELLS ,lcsh:RC648-665 ,maturation ,urogenital system ,SIGNAL TRANSDUCTION ,PROLIFERATION ,Cell cycle ,Sertoli cell ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,purl.org/becyt/ford/3 [https] ,Signal transduction ,signal transduction - Abstract
Sertoli cells are somatic cells present in seminiferous tubules which have essential roles in regulating spermatogenesis. Considering that each Sertoli cell is able to support a limited number of germ cells, the final number of Sertoli cells reached during the proliferative period determines sperm production capacity. Only immature Sertoli cells, which have not established the blood-testis barrier, proliferate. A number of hormonal cues regulate Sertoli cell proliferation. Among them, FSH, the insulin family of growth factors, activin, and cytokines action must be highlighted. It has been demonstrated that cAMP/PKA, ERK1/2, PI3K/Akt, and mTORC1/p70SK6 pathways are the main signal transduction pathways involved in Sertoli cell proliferation. Additionally, c-Myc and hypoxia inducible factor are transcription factors which participate in the induction by FSH of various genes of relevance in cell cycle progression. Cessation of proliferation is a prerequisite to Sertoli cell maturation accompanied by the establishment of the blood-testis barrier. With respect to this barrier, the participation of androgens, estrogens, thyroid hormones, retinoic acid and opioids has been reported. Additionally, two central enzymes that are involved in sensing cell energy status have been associated with the suppression of Sertoli cell proliferation, namely AMPK and Sirtuin 1 (SIRT1). Among the molecular mechanisms involved in the cessation of proliferation and in the maturation of Sertoli cells, it is worth mentioning the upregulation of the cell cycle inhibitors p21Cip1, p27Kip, and p19INK4, and of the gap junction protein connexin 43. A decrease in Sertoli cell proliferation due to administration of certain therapeutic drugs and exposure to xenobiotic agents before puberty has been experimentally demonstrated. This review focuses on the hormones, locally produced factors, signal transduction pathways, and molecular mechanisms controlling Sertoli cell proliferation and maturation. The comprehension of how the final number of Sertoli cells in adulthood is established constitutes a pre-requisite to understand the underlying causes responsible for the progressive decrease in sperm production that has been observed during the last 50 years in humans. Fil: Meroni, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Galardo, Maria Noel Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Rindone, Gustavo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Gorga, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Riera, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Cigorraga, Selva Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
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- 2019
49. SUN-214 Neonatal Metformin Administration Exerts a Suppressive Effect on Sertoli Cell Proliferation in Rats
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Agostina Gorga, Maria Fernanda Riera, Maria Noel Lujan Galardo, Gustavo Marcelo Rindone, Silvina Beatriz Meroni, Mariano G. Buffone, Vanina Gabriela Da Ros, María del Carmen Camberos, and Eliana Herminia Pellizzari
- Subjects
business.industry ,Male Reproduction: From Bench to Bedside ,Endocrinology, Diabetes and Metabolism ,medicine ,Sertoli cell proliferation ,Reproductive Endocrinology ,Pharmacology ,business ,Metformin ,medicine.drug - Abstract
Sertoli cell (SC) proliferation, a factor defining SC population size, occurs during a restricted period of time. In rats, SCs start proliferating during fetal development and undergo mitosis for up to 15 days after birth. In humans, SCs proliferate during fetal and neonatal periods for up to 6 months after birth and there is a second stage of proliferation at the onset of puberty. Metformin (MET), a first line anti-hyperglycemic agent, is used in pediatric population at ages when SCs are still proliferating. In addition to its strong anti-diabetic properties, numerous studies have demonstrated that MET has anti-proliferative activity (1). In this context, it has been demonstrated in SC cultures obtained from 8-day old rats that MET decreases FSH-stimulated SC proliferation and that this decrease is accompanied by a reduction in Cyclin D1, D2, E1 and E2 expression and an increase in cell cycle inhibitor p21Cip expression (2). The aim of this study was to analyze the potential effect of in vivo neonatal administration of Metformin on rat Sertoli cell proliferation and its impact on the spermatogenic capacity in adult animals. Male Sprague Dawley rat pups were randomly assigned at postnatal day 3 (PND3) to the following groups: MET (receiving daily 200 mg/kg MET i.p., from day 3 to 7 inclusive) and control (receiving daily sterile saline solution i.p). At PND8, SCs were isolated from a set of animals to analyze the expression of cell cycle regulators and of SC maturation markers by RT-qPCR. Another set of animals were injected with BrdU (50 mg/kg) 90 min before sacrifice to evaluate cell proliferation. Our results showed that MET group exhibited a significant decrease in BrdU incorporation in SCs compared to controls (p
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- 2019
50. Effect of resveratrol on Sertoli cell proliferation
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Selva B. Cigorraga, Maria Fernanda Riera, Silvina Beatriz Meroni, Eliana Herminia Pellizzari, Agostina Gorga, Maria Noel Lujan Galardo, Mariana Regueira, María del Carmen Camberos, and Gustavo Marcelo Rindone
- Subjects
Male ,0301 basic medicine ,CIENCIAS MÉDICAS Y DE LA SALUD ,Sertoli cell proliferation ,Biology ,Resveratrol ,Biochemistry ,Proto-Oncogene Proteins c-myc ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Sirtuin 1 ,Animals ,RNA, Messenger ,Molecular Biology ,Cells, Cultured ,RESVERATROL ,Cell Proliferation ,Sertoli Cells ,PROLIFERATION ,Cell Biology ,Bioquímica y Biología Molecular ,Molecular biology ,Neoplasm Proteins ,Rats ,SERTOLI ,Sprague dawley ,Medicina Básica ,030104 developmental biology ,Gene Expression Regulation ,chemistry ,SIRTUIN 1 ,Follicle Stimulating Hormone - Abstract
Resveratrol (RSV), a polyphenolic compound largely found in red grape skin, has been used as a nutritional supplement as it exhibits beneficial health effects, such as anticancer, cardioprotective, antiaging, and anti-inflammatory. Particularly, it has been shown that it participates in the mechanisms involved in cell proliferation. Sirtuin 1 (SIRT1) is considered a well-known RSV effector. Noteworthy, Sirt1-knockout animals are infertile. The aim of this study was, first, to determine whether RSV has any effect on Sertoli cell proliferation and, second, whether SIRT1, a putative target of RSV, is present in immature Sertoli cells. Sertoli cell cultures obtained from 8-day-old rats, which actively proliferate, were treated with RSV (10 and 50 µM) under basal and follicle-stimulating hormone (FSH)-stimulated conditions. Bromodeoxyuridine (BrdU) incorporation and the expression of cyclins D1, D2, D3, E1, and E2 and the Cip/Kip cell cycle inhibitors p21Cip and p27Kip were analyzed. RSV decreased BrdU incorporation and cyclins D1, D2, E1, and E2 expression and increased p21Cip and p27Kip messenger RNA (mRNA) levels. RSV also decreased FSH-stimulated BrdU incorporation and cyclins D1 and D2 mRNA levels. The effect of RSV on cMYC was also analyzed. RSV treatment did not modify basal and FSH-stimulated cMyc expression; however, it inhibited basal and FSH-stimulated cMYC transcriptional activity, suggesting a role of cMYC in RSV effects. Additionally, Sirt1 was detected in immature Sertoli cells. Altogether, these results suggest that RSV possibly, by activating SIRT1 and regulating cMYC transcriptional activity, participates in the regulation of immature Sertoli cell proliferation. Fil: Gorga, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Rindone, Gustavo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Regueira, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Pellizzari, Eliana Herminia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Camberos, Maria del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Cigorraga, Selva Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Riera, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Galardo, Maria Noel Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Meroni, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
- Published
- 2018
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