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Arsenic is one of the most hazardous environmental contaminants, which adversely affects the dynamics of male reproductive system. Fisetin (FIS) is a bioactive flavonoid, which is known to exert strong antioxidative effects. Therefore, the current research was planned to evaluate the alleviative efficacy of FIS against arsenic-induced reproductive damages. Forty-eight male albino rats were divided into 4 groups (n = 12), which were treated as follows: (1) Control, (2) Arsenic-intoxicated group (8 mg kg−1), (3) Arsenic + FIS-treated group (8 mg kg−1 + 10 mg kg−1), and (4) FIS-treated group (10 mgkg−1). After 56 days of treatment, the biochemical, lipidemic, steroidogenic, hormonal, spermatological, apoptotic and histoarchitectural profiles of rats were analyzed. Arsenic intoxication reduced the enzymatic activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GSR), in addition to glutathione (GSH) level. Conversely, the levels of thiobarbituric acid reactive substance (TBARS) and reactive oxygen species (ROS) were increased. Moreover, it escalated the level of low-density lipoprotein (LDL), triglycerides and total cholesterol, while declining the level of high-density lipoprotein (HDL). Furthermore, steroidogenic enzymes expressions, 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (CYP11A1) and 17α-hydroxylase/17, 20-lyase (CYP17A1), were found to be reduced, which brought down the level of testosterone. Besides, the levels of gonadotropins (LH and FSH) were decreased. Additionally, a decline in sperm mitochondrial membrane potential (MMP), motility, epididymal sperm count and hypo-osmotic swelling (HOS) coil-tailed sperms was observed, whereas the dead sperms and structural damages (head, midpiece and tail) of sperms were escalated. Moreover, arsenic exposure up-regulated the mRNA expressions of apoptotic markers, namely Bax and caspase-3, whereas lowered the expression of anti-apoptotic marker, Bcl-2. In addition, it induced histoarchitectural changes in testes of rats. However, FIS treatment resulted in remarkable improvements in testicular and sperm parameters. Therefore, it was inferred that FIS could serve as a therapeutic candidate against arsenic-generated male reproductive toxicity attributing to its anti-oxidant, anti-lipoperoxidative, anti-apoptotic, and androgenic efficacy. [ABSTRACT FROM AUTHOR]

Granulosa cells (GCs) are essential for follicular growth, oocyte maturation, and steroidogenesis in the ovaries. Interleukin (IL)-11 is known to play a crucial role in the decidualization of the uterus, however, the expression of the IL-11 system (IL-11, IL-11Rα, and gp130) in the bovine ovary and its exact role in GCs have not been extensively studied. In this study, we identified the IL-11 signaling receptor complex in the bovine ovary and investigated the regulatory effects and underlying mechanism of IL-11Rα on the proliferation and steroidogenesis of GCs. We observed that the IL-11 complex was highly expressed in the GCs of large follicles. IL-11Rα knockdown significantly inhibited GC proliferation by inducing cell cycle arrest at the G1 phase, along with a significant downregulation of proliferating cell nuclear antigen (PCNA) and Cyclin D1 (CCND1) protein, and induced GC apoptosis by significantly upregulating the ratio of BCL-2-associated X protein (BAX) and B-cell lymphoma-2 (BCL-2). In addition, IL-11Rα knockdown attenuated the Janus kinase (JAK) 1–signal transducer and activator of transcription 3 (STAT3) signaling, which is related to cell proliferation and apoptosis. Furthermore, the enzyme-linked immunosorbent assay (ELISA) indicated that IL-11Rα silencing decreased the basal and forskolin (FSK)-stimulated secretions of estradiol and progesterone in GC culture medium concomitantly with a remarkable decrease in cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and steroidogenic acute regulatory protein (StAR). We subsequently determined that this reduction in steroidogenesis was in parallel with the decrease in phosphorylations of protein kinase A (PKA) substrates, cAMP-response element binding protein (CREB), extracellular regulated protein kinase (ERK) 1/2, and p38 mitogen-activated protein kinase (MAPK). Taken together, these data indicate that the effects of IL-11/IL-11Rα on the proliferation and steroidogenesis in bovine GCs is mediated by the JAK1-STAT3, PKA-CREB, p38MAPK, and ERK1/2 signaling pathways. Our findings provide important insights into the local action of the IL-11 system in regulating ovarian function. [ABSTRACT FROM AUTHOR]

Diallyl trisulfide (DAT) is a biologically active component of garlic essential oil and exhibits multi-targeted activity against many organisms. The current study tested the capacity of DAT to decrease the male fertility of Sitotroga cerealella. The effects on testis morphology, sperm number, motility, and lipid homeostasis were observed in adult males fumigated with DAT at a dose of 0.01 μL/L in air. The results indicated that the DAT significantly decreased the dimorphic sperm number. Meanwhile, the ultrastructural analysis of the sperm showed that the DAT caused malformed and aberrant structures of mitochondrial derivatives of dimorphic sperm. Additionally, the lipid homeostasis and ATP contents in the male adults were significantly decreased after treatment. Moreover, the total sperm motility was reduced, while the wave-propagation velocity, amplitude, frequency, and wavelength were significantly decreased compared with the controls. Overall, this study reported, for the first time, that DAT impairs energy metabolism, inhibits dimorphic spermatogenesis, and decreases sperm motility, while these abnormalities in sperm lead to adult-male infertility. [ABSTRACT FROM AUTHOR]

Activins and inhibins are unique members of the transforming growth factor-β (TGFβ) family of growth factors, with the ability to exert autocrine, endocrine, and paracrine effects in a wide range of complex physiologic and pathologic processes. Although first isolated within the pituitary, emerging evidence suggests broader influence beyond reproductive development and function. Known roles of activin and inhibin in angiogenesis and immunity along with correlations between gene expression and cancer prognosis suggest potential roles in tumorigenesis. Here, we present a review of the current understanding of the biological role of activins and inhibins as it relates to ovarian cancers, summarizing the underlying signaling mechanisms and physiologic influence, followed by detailing their roles in cancer progression, diagnosis, and treatment. [ABSTRACT FROM AUTHOR]

Methotrexate (MXT) is a medication used for cancer and rheumatoid treatment with severe organs toxicity as a side effect. Paullinia cupana (Guarana) is a plant with pleiotropic functions used to overcome the side effects of some chemotherapeutic medications. Current study aimed to examine the possible protective effect of guarana against oxidative stress induced by a single dose of MTX in testis. Forty male mice were divided into 4 groups (8 weeks old; 30 g weight), 1st group is negative control. The 2nd group is positive intoxicated group, received a single dose of MTX intraperitoneally (IP; 20 mg/kg BW in saline) on day 7. The 3rd group received guarana seed extract orally (300 mg/kg BW daily) for 12 days. The protective group was given guarana seed extract orally for 1 week, then on day 7 injected with MTX, and continued with guarana for extra 5 days. Blood was taken for biochemical measurement (hormones, antioxidants, cytokines, and oxidative stress biomarkers). Testicular tissues were taken for gene quantification (qRT-PCR), testicular oxidative stress activity (malondialdehyde; MDA, and SOD) and comet assay (sperm DNA damage), and histopathological changes at the end of experimental design. MTX intoxication caused a decrease in testicular SOD, GSH, and catalase and an increase in serum and tissue levels of MDA. Biomarkers of oxidative stress were increased by MTX intoxication, and were ameliorated by guarana administration to MTX-intoxicated mice. Guarana prevented the increase in IL-1β and IL-6 levels compared to mice intoxicated with MTX alone. MTX upregulated the expression of caspase-3 and downregulated Bcl-2 expression using qRT-PCR analysis. These negative impacts of MTX were protected by guarana pre-administration. MTX decreased reproductive hormones and altered spermogram parameters (sperm concentration and motility, and percentage of live and dead sperms). In addition, the mRNA expression of steroidogenesis-associated genes, such cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 17β hydroxyl steroid dehydrogenase (17β-HSD) was downregulated in the MTX-treated group, all were prevented by guarana administration. The sperm DNA damage revealed by a comet assay was increased in MTX group and was reversed to control levels by guarana supplementation. Finally, testis histology of MTX-group showed marked spermatocytes vacuolization and a decrease in spermatogenesis. Guarana administration abrogated histopathological changes reported in the Leydig cells and testicular tissues. In conclusion, guarana has the potential as a supplement medication to antagonize testicular oxidative stress induced by methotrexate. [ABSTRACT FROM AUTHOR]

There is ambiguous evidence that high-fructose diet can induce toxicity in different organ systems but its endocrine disrupting effects by abnormal changes in female reproductive organs is poorly evidenced. This study aimed to address the reproductive safety of high fructose diet through clinical, biochemical, hormonal, histopathological, and immunohistochemical analysis. For this purpose, 5–6 weeks mature female Wistar rats were divided in three groups and each five animals/group exposed to standard chow + water + HFCS-55, standard chow + water + sucrose 75%w/v and standard chow + water for 90 days. Remarkable increase in most lipid profile factors and total body weights of HFCS-55 fed rats and sucrose fed rats were detected in similar pattern compared to control. At the same time, a battery of differential signs and symptoms in HFCS-fed groups including squamous metaplasia in the uterine tissue and ovarian congestion, significant increase in FSH and LH levels, meaningful decreased serum testosterone and 17β-estradiol levels, and strong androgen receptor expression in ovaries and uterine of HFCS group of animals were recorded compared to other two study groups. These thought-provoking signs and signals of fructose induced reproductive toxicity in this model emphasis the contribution of HFCS-55 to deteriorated ovarian and endometrial health and increased risk primary ovarian insufficiency (POI) in women. [ABSTRACT FROM AUTHOR]

Background: Reliable predictive models for predicting excessive and poor ovarian response in controlled ovarian stimulation (COS) is currently lacking. The dynamic (D) inhibin B, which refers to increment of inhibin B responding to exogenous gonadotropin, has been indicated as a potential predictor of ovarian response. Objective: To establish mathematical models to predict ovarian response at the early phase of COS using Dinhibin B and other biomarkers. Materials and methods: Prospective cohort study in a tertiary teaching hospital, including 669 cycles underwent standard gonadotropin releasing hormone (GnRH) antagonist ovarian stimulation between April 2020 and September 2020. Early Dinhibin B was defined as an increment in inhibin B from menstrual day 2 to day 6 through to the day of COS. Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression with 5-fold cross-validation was applied to construct ovarian response prediction models. The area under the receiver operating characteristic curve (AUC), prevalence, sensitivity, and specificity were used for evaluating model performance. Results: Early Dinhibin B and basal antimüllerian hormone (AMH) levels were the best measures in building models for predicting ovarian hypo- or hyper-responses, with AUCs and ranges of 0.948 (0.887–0.976) and 0.904 (0.836–0.945) in the validation set, respectively. The contribution of the early Dinhibin B was 67.7% in the poor response prediction model and 56.4% in the excessive response prediction model. The basal AMH level contributed 16.0% in the poor response prediction model and 25.0% in the excessive response prediction model. An online website based tool (http://121.43.113.123:8001/) has been developed to make these complex algorithms available in clinical practice. Conclusion: Early Dinhibin B might be a novel biomarker for predicting ovarian response in IVF cycles. Limiting the two prediction models to the high and the very-low risk groups would achieve satisfactory performances and clinical significance. These novel models might help in counseling patients on their estimated ovarian response and reduce iatrogenic poor or excessive ovarian responses. [ABSTRACT FROM AUTHOR]

(1) Background: Icariin is the main component of the Chinese herb Epimedium. A number of studies have shown that it alleviates abnormal lipid metabolism. However, it is not clear whether and how icariin can ameliorate hepatic steatosis with polycystic ovary syndrome (PCOS). This study was designed to explore the anti-hepatosteatosis effect of icariin in rats with polycystic ovary syndrome. (2) Methods: Female Sprague Dawley(SD)rats were treated with a high-fat diet and letrozole for 21 days to make nonalcoholic fatty liver disease (NAFLD) in the polycystic ovary syndrome model. Then model rats were treated with icariin (by gavage, once daily) for 28 days. Serum hormones and biochemical variables were determined by ELISA or enzyme. RNA-sequence analysis was used to enrich related target pathways. Then, quantitative Real-time PCR (qRT-PCR) and Western blot were performed to verify target genes and proteins. (3) Results: Icariin treatment reduced excess serum levels of Testosterone (T), Estradiol (E2), Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), LH/FSH ratio, insulin, triglycerides (TG), and aspartate aminotransferase (AST) in high-fat diet (HFD) and letrozole fed rats. Meanwhile, icariin ameliorated HFD and letrozole-induced fatty liver, as evidenced by a reduction in excess triglyceride accumulation, vacuolization, and Oil Red O staining area in the liver of model rats. Results of RNA-sequencing, western blotting, and qRT-PCR analyses indicated that icariin up-regulated fatty acid translocase (CD36), in mitochondria, and peroxisome proliferator-activated receptor α (PPARα) expression, which led to the enhancement of fatty acid oxidation molecules, such as cytochrome P450, family 4, subfamily a, polypeptide 3 (CYP4A3), carnitine palmitoyltransferase 1 α (CPT1α), acyl-CoA oxidase 1 (ACOX1), medium-chain acyl-CoA dehydrogenase (MCAD), and long-chain acyl-CoA dehydrogenase (LCAD). Besides, icariin reduced lipid synthesis, which elicited stearoyl-Coenzyme A desaturase 1 (SCD1), fatty acid synthase (FASN), and acetyl-CoA (ACC). (4) Conclusion: Icariin showed an ameliorative effect on hepatic steatosis induced by HFD and letrozole, which was associated with improved fatty acid oxidation and reduced lipid accumulation in the liver. [ABSTRACT FROM AUTHOR]

Background: The lack of clinically useful biomarkers for predicting micro-TESE outcomes in males with idiopathic NOA. To find clinically reliable serum reproductive hormone markers to predict the outcome of sperm retrieval in men with idiopathic NOA undergoing micro-TESE. Methods: We analyzed the clinical data of 168 men with idiopathic NOA treated with micro-TESE. The clinical predictors of a successful sperm retrieval were put to the test using logistic regression analysis. The clinical net benefit was calculated using a decision-curve analysis, and the predictive power of each variable was assessed using the ROC-derived area under the curve. Result: Between positive group and negative group for sperm retrieval, there was a statistically significant difference in INHB, AMH, and INHB/AMH. AMH, INHB, and INHB/AMH were each independent predictors of successful sperm retrieval, with INHB (OR1.02, p = 0.03), AMH (OR0.85, p = 0.01), INHB/AMH (OR1.08, p < 0.01). The ROC curve determined the optimal cut-off values for serum INHB and INHB/AMH in positive sperm retrieval patients undergoing micro-TESE. 21.51 pg/mL was the cut-off value for INHB. The cut-off value for INHB/AMH was 3.19, which had a 86.3% sensitivity and a 53.8% specificity. Using INHB and INHB/AMH prior to micro-TESE sperm retrieval in idiopathic NOA patients improved the net benefit of positive sperm retrieval, and the net benefit score of INHB/AMH was better than that of INHB, according to decision analysis curves. Conclusion: Serum INHB have predictive value for sperm retrieval outcomes in idiopathic NOA patients undergoing micro-TESE. Combining INHB and AMH, INHB/AMH seems to be a better predictor. [ABSTRACT FROM AUTHOR]

Gestation in sheep necessitates the support of nutrients to avoid early embryonic mortalities. Therefore, this study investigates the effects of supplementing either L-arginine or Spirulina alga in the first trimester on the pregnancy rate, litter size, inhibin, insulin, IGF-I, CO Q10, and bone morphogenetic peptide 15 (BMP15) in maternal circulation. Animals were offered barley (500 g/head/day, 14% CP), alfalfa hay (1 kg/head/day, 12% CP), clean water, and balanced salt block licks as free choices. Forty Noemi and Najdi ewes were randomly allotted into three groups: control (C, n = 8), L-arginine (ARG, n = 16), and Spirulina (SP, n = 16). All females were implanted with CIDR for ten days. On days 8, 9, and 10, treated ewes were given a protocol comprised of human recombinant FSH at descending doses (50, 50, 40, 40, and 30, 30 IU, A.M, and P.M, respectively). At the fifth dose, animals were given an equivalent dose of hCG (240 IU). After CIDR withdrawal, ewes were exposed to fertile rams for mating. SP-ewes were orally given 50 ml (2%) Spirulina, and ARG-ewes were given 50 ml (35 mg/kg BW) L-arginine daily for 50 days postbreeding. Blood inhibin, insulin, IGF-I, CO Q10, and BMP15 were determined throughout gestation until parturition. The findings indicated that the conception rates were 25, 75, and 87.5% in C, ARG, and SP, respectively (P < 0.05). The percent of ewes giving birth to twins was 0, 25, and 50% in C, ARG, and SP, respectively (P < 0.05). The survival rates were 100, 81.8, and 83.3%, respectively. Birth weight was 5.6, 3.2, and 3.4 kg in C, ARG, and SP, respectively. Weaning weights were 28.3, 25.6, and 27.2 kg in C, ARG, and SP, respectively. BMP-15 was reduced (P < 0.05) in ARG than in C and SP. However, SP decreased (P < 0.05) inhibin more than in C and ARG. ARG and SP increased (P < 0.05) insulin than in C, whereas SP decreased (P < 0.05) IGF-I. SP increased CO Q10 compared with ARG. Ewes bearing twins revealed higher (P < 0.05) IGF-I (8.57 ng/ml) than those bearing singles (4.63 ng/ml); however, BMP-15 was higher in single (796.6 pg/ml) than in twin-bearing (387.5 pg/ml) ewes. In conclusion, providing early-gestating ewes with Spirulina enhances maternal health, productivity, and reproductive outcomes. [ABSTRACT FROM AUTHOR]

Simultaneous knockout of the neuroendocrine marker genes Ptprn and Ptprn2, which encode the protein tyrosine phosphatase receptors N and N2, causes infertility in female mice while males are fertile. To elucidate the mechanism of the sex-specific roles of Ptprn and Ptprn2 in mouse reproduction, we analyzed the effects of their double knockout (DKO) on the hypothalamic-pituitary–gonadal axis. In DKO females, delayed puberty and lack of ovulation were observed, complemented by changes in ovarian gene expression and steroidogenesis. In contrast, testicular gene expression, steroidogenesis, and reproductive organs development were not significantly affected in DKO males. However, in both sexes, pituitary luteinizing hormone (LH) beta gene expression and LH levels were reduced, as well as follicle-stimulating hormone beta gene and gonadotropin-releasing hormone (GnRH) gene, while the calcium-mobilizing and LH secretory actions of GnRH were preserved. Hypothalamic Gnrh1 and Kiss1 gene expression was also reduced in DKO females and males. In parallel, a significant decrease in the density of immunoreactive GnRH and kisspeptin fibers was detected in the hypothalamic arcuate nucleus of DKO females and males. The female-specific kisspeptin immunoreactivity in the rostral periventricular region of the third ventricle was also reduced in DKO females, but not in DKO males. These data indicate a critical role of Ptprn and Ptprn2 in kisspeptin-GnRH neuronal function and sexual dimorphism in the threshold levels of GnRH required to preserve reproductive functions. [ABSTRACT FROM AUTHOR]

Background: Differences of sex development (DSD) are congenital conditions linked to atypical development of chromosomal, gonadal, or anatomical sex. Objective: The aim of this study was to demonstrate our experiences at the Diabetes Endocrine and Metabolism Pediatric Unit (DEMPU), Faculty of Medicine, Cairo University in the field of DSD by focusing on the clinical presentation, laboratory profile, classification, and etiological diagnosis of these conditions. In addition, the present study intended to delineate the importance of serum anti-Müllerian hormone (AMH) and inhibin B in detecting the presence of functioning testicular tissue. Methods: This cohort study included 451 infants and children with various clinical presentations of DSD. The study performed a retrospective analysis on medical records of established DSD cases to evaluate the clinical importance of AMH and inhibin B. In addition, newly diagnosed patients were prospectively analyzed. Results: Three hundred thirty-six (74.5%) patients were 46,XY DSD, 98 (21.7%) were 46,XX DSD, 14 patients had other karyotypes and 3 had missing karyotypes. Among the 46XY DSD patients, the most common cause was partial androgen insensitivity. In contrast, congenital adrenal hyperplasia constituted the most common diagnosis in 46,XX DSD cases. The cut off value of serum AMH was 14.5 ng/ml with 100% sensitivity and 55.1% specificity. Conclusion: Partial androgen insensitivity was the most important cause of 46, XY DSD in Egyptian children, and congenital adrenal hyperplasia was the most common cause of 46,XX DSD. AMH was valuable in detecting functioning testicular tissue. [ABSTRACT FROM AUTHOR]

In a previous work, the common gonadotrophic hormone α-subunit (ag-GTHα), the ag-FSH β- and ag-LH β-subunit cDNAs, were isolated and characterized by our research group from A. gigas pituitaries, while a preliminary synthesis of ag-FSH was also carried out in human embryonic kidney 293 (HEK293) cells. In the present work, the cDNA sequence encoding the ag-growth hormone (ag-GH) has also been isolated from the same giant Arapaimidae Amazonian fish. The ag-GH consists of 208 amino acids with a putative 23 amino acid signal peptide and a 185 amino acid mature peptide. The highest identity, based on the amino acid sequences, was found with the Elopiformes (82.0%), followed by Anguilliformes (79.7%) and Acipenseriformes (74.5%). The identity with the corresponding human GH (hGH) amino acid sequence is remarkable (44.8%), and the two disulfide bonds present in both sequences were perfectly conserved. Three-dimensional (3D) models of ag-GH, in comparison with hGH, were generated using the threading modeling method followed by molecular dynamics. Our simulations suggest that the two proteins have similar structural properties without major conformational changes under the simulated conditions, even though they are separated from each other by a >100 Myr evolutionary period (1 Myr = 1 million years). The sequence found will be used for the biotechnological synthesis of ag-GH while the ag-GH cDNA obtained will be utilized for preliminary Gene Therapy studies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Adenomatoid tumors are rare benign neoplasms of mesothelial histogenesis. They are usually located in the genitourinary system in men and women, although exceptional cases of extragenital manifestation have been reported, for example in the adrenal gland. These tumors show multiple histological patterns, among which the angiomatoid, adenoid and cystic stand out. CLINICAL CASE: A 39-year-old male patient with an adrenal adenomatoid tumor, identified by chance, with follow-up in a chronic alcohol consumption rehabilitation program. The tumor measured 46 x 30 x 46 mm, was white and homogeneous. Histologically, mesothelial cells in an angiomatoid and adenoid pattern were observed, accompanied by lymphoid aggregates, with positivity for Cam 5.2, CK7, calretinin and podoplanin, and negativity for inhibin, synaptophysin, Melan A and CK20. CONCLUSIONS: Adenomatoid tumors are benign neoplasms of mesothelial origin, which can appear in atypical locations, such as the adrenal gland. It is important to know its characteristics and differential diagnoses because it can pose a clinical, radiological, and histological challenge. [ABSTRACT FROM AUTHOR]

There remains an insufficiency of data on the long-term toxicological profile of Garcinia kola Heckel and its extract, Kolaviron (KV), despite several studies on its pharmacological effects. This research was designed to investigate the long-term histopathological, hematological, biochemical, hormonal, reproductive, and oxidative effects of 90 days administration of KV to male and female rats, as well as additional 30 days reversibility study to assess the potential for reversal of induced effects. Fifty-six male and female Wistar rats divided into four groups were treated orally with distilled water/propylene glycol, 20 mg/kg KV, 100 mg/kg KV, and 500 mg/kg KV for 90 days. At the end of 90 days and 30 additional days of reversibility study, 5 ml blood was collected from animals for relevant analyses. Vital organs were harvested for histopathological assessments. In this study, KV did not elicit any adverse effect on histopathological presentations of vital organs which were generally non-abnormal. There was significant increase (p < 0.05) in LEU, MON, EOS%, BAS%, HCT (male animals) and LYM%, EOS%, BAS%, RBC, hemoglobin and MCH (female animals). There was significant diminution (p < 0.05) in cholesterol, triglycerides, LDL, and VLDL levels, with significant increase (p < 0.05) in HDL level in both male and female animals. KV elicited a non-significant increase in sperm count accompanied by a significant increase (p < 0.05) in levels of Follicle stimulating hormone (FSH) and testosterone in male rats. Furthermore, KV elicited significant (p < 0.001–0.05) elevation in the levels of GSH, SOD and CAT, and diminution in the level of MDA. The findings in this study suggest that long-term administration of KV is considerably safe with some variations in response between male and female animals. The possible sustenance of observed effects after cessation of KV administration, lipid lowering, erythropoiesis inducing, and immune system boosting activities of KV were confirmed in this study. [ABSTRACT FROM AUTHOR]

Medicinal plants offer an important therapeutic resource in treatment of male infertility. We aim to evaluate the possible therapeutic effects of Salvia balansae on metabolic disorders and testicular dysfunction resulting from a high-fat diet (HFD). Antioxidant activity of aqueous extract of S. balansae leaves was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assay and total antioxidant capacity (TAC) assay. Antidiabetic activity was determined by α-amylase inhibition. In vivo, HFD was administered in Wistar rats for 18 weeks and aqueous extract of S. balansae for the last 6 weeks (200 mg/Kg of body weight/day). At the term of experimentation, testosterone and some plasma parameters were analyzed and removed testes were subjected to a histomorphometric study. Our results show high levels of phenolic components in aqueous extract of S. balansae and significant antioxidant and antidiabetic activity. HFD increases body weight, causes type 2 diabetes, dyslipidemia, liver failure and inflammation. Also, HFD decreases testosterone and alters testis histological structure (seminiferous tubular degeneration, impaired spermatogenesis and interstitial fibrosis). Treatment of HFD rats with extract of S. balansae normalizes body weight and plasma parameters, increases testosterone and regenerates testicular structure and function. In summary, S. balansae could reduce metabolic complications induced by HFD and serve the basis for developing a new therapy for testicular dysfunction. [ABSTRACT FROM AUTHOR]

Premature ovarian failure (POF) is described as a loss of oocytes and the absence of folliculogenesis and is considered an adverse effect of chemotherapeutic drugs, which leads to infertility. Subsequently, the existing inquiry was achieved by exploring the potential suspicious influences of lemon peel extract (LPE), and resveratrol (RES) on cyclophosphamide (CPA) induced-POF. The results showed that CPA-induced POF significantly decreased serum estradiol (E2) and progesterone levels, along with a considerable rise in serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Moreover, CPA administration to rats significantly increased the serum level of Malondialdehyde (MDA) and significantly lowered the levels of reduced glutathione (GSH) and superoxide dismutase (SOD); in addition, it increased nuclear factor kappa B (NF-κB) levels, tumor necrosis factor-α (TNF-α), as well as cyclooxygenase 2 (COX-2) with the spread expression of inducible nitric oxide synthase (iNOS) mRNA levels and caspase-3 (Casp3) levels in ovarian tissues versus the control rats. However, treatment with LPE and RES suppressed the triggering of NF- κB pathways, evidenced by a considerable reduction in Casp3 & iNOS mRNA expression level and significant ameliorative effects in all evaluated parameters, as confirmed by the histological and immunohistochemical investigation when comparing the model group. In overall findings, both lemon peel extract and resveratrol can mitigate the adverse effects of CPA-induced POF. Most crucially, its combination therapy is a promising pharmacological agent for this disease. [ABSTRACT FROM AUTHOR]

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To determine whether preimplantation genetic testing (PGT) is associated with a change in maternal serum analyte levels in pregnancies conceived via in vitro fertilization (IVF). Retrospective cohort of singleton and twin IVF pregnancies with available first- or second-trimester serum analyte data from 01/2014 to 09/2019. Multiple of the median (MoM) values for free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP), inhibin A, and unconjugated estriol, were compared between two groups: pregnancies conceived after transfer of PGT screened euploid embryos vs. those conceived after transfer of untested embryos. Multiple linear regression of log MoM values with F test was performed to adjust for potential confounders. Nine hundred and sixty-two singleton and 165 twin IVF pregnancies with serum analyte data available for analysis were included. PGT was associated with a higher median first- and second-trimester AFP compared to no PGT in singletons (1.23 MoM vs. 1.13 MoM; parameter estimate [PE] 1.08, 95% CI 1.00–1.17, p=.04, and 1.21 MoM vs. 1.07 MoM; PE 1.07, 95% CI 1.01–1.13, p=.01, respectively). PGT was also associated with a lower median PAPP-A compared to no PGT in twins (0.75 MoM vs. 1.18 MoM, PE 0.74, 95% CI 0.60–0.92, p=.006). Our data suggest that PGT is associated with higher maternal serum levels of second-trimester AFP in singleton and lower levels of first-trimester PAPP-A in twin pregnancies conceived via IVF. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 9 (GDF9) was the first oocyte-specific growth factor identified; however, most information about GDF9 functions comes from studies in the mouse model. In this study, we created a mutant for Gdf9 gene (gdf9-/-) in zebrafish using TALEN approach. The loss of Gdf9 caused a complete arrest of follicle development at primary growth (PG) stage. These follicles eventually degenerated, and all mutant females gradually changed to males through sex reversal, which could be prevented by mutation of the male-promoting gene dmrt1. Interestingly, the phenotypes of gdf9-/- could be rescued by simultaneous mutation of inhibin α (inha-/-) but not estradiol treatment, suggesting a potential role for the activin-inhibin system or its signaling pathway in Gdf9 actions. In gdf9 null follicles, the expression of activin βAa (inhbaa), but not βAb (inhbab) and βB (inhbb), decreased dramatically; however, its expression rebounded in the double mutant (gdf9-/-;inha-/-). These results indicate clearly that the activation of PG follicles to enter the secondary growth (SG) requires intrinsic factors from the oocyte, such as Gdf9, which in turn works on the neighboring follicle cells to trigger follicle activation, probably involving activins. In addition, our data also support the view that estrogens are not involved in follicle activation as recently reported. Author summary: Follicles are the basic structural and functional units of the ovary. Each follicle consists of an oocyte and surrounding somatic follicle cells. The growth and maturation of follicles or folliculogenesis is controlled by a variety of hormones and local factors. It has been known for decades that the oocyte in the follicle plays an active role in controlling folliculogenesis by releasing various regulatory factors, among which the growth differentiation factor 9 (GDF9) is the best characterized one. In this study, we used gene editing method to delete the gene for GDF9 (gdf9) in the zebrafish. We discovered that without gdf9 gene (mutant), the follicles could not develop to advanced stages and the females were therefore infertile. Interestingly, when inhibin (a hormone from the ovary) was lost simultaneously, the follicles in the gdf9 mutant resumed growth and development. We hypothesized that the resumption of follicle growth in the double mutant of gdf9 and inha was likely due to increased activity of activin. [ABSTRACT FROM AUTHOR]

Microcystic stromal tumor (MST) is a rare type of pure stromal tumor in the category of ovarian sex cord-stromal tumors. It is characterized by a distinctive microcystic appearance with bland tumor cells. Although the pathological diagnosis can be straightforward based on the typical histomorphology in most MSTs, the cases with morphologic variation can pose a diagnostic challenge due to unfamiliarity of pathologists with the histologic spectrum of MST and its negativity for inhibin and calretinin, the commonly used sex cord-stromal markers. The coexistence between MST and mucinous epithelial tumor is extremely rare. We present the first case, to our knowledge, of ovarian MST with predominant bizarre nuclei coexisting with mucinous cystadenoma in a pregnant woman. The histomorphology in this case presents a diagnostic challenge and raises differential diagnosis for a wide variety of ovarian malignant neoplasms including nonneoplastic lesions. [ABSTRACT FROM AUTHOR]

Activin and inhibin are both dimeric proteins sharing the same β subunits that belong to the TGF-β superfamily. They are well known for stimulating and inhibiting pituitary FSH secretion, respectively, in mammals. In addition, activin also acts as a mesoderm-inducing factor in frogs. However, their functions in development and reproduction of other species are poorly defined. In this study, we disrupted all three activin/inhibin β subunits (βAa, inhbaa; βAb, inhbab; and βB, inhbb) in zebrafish using CRISPR/Cas9. The loss of βAa/b but not βB led to a high mortality rate in the post-hatching stage. Surprisingly, the expression of fshb but not lhb in the pituitary increased in the female βA mutant together with aromatase (cyp19a1a) in the ovary. The single mutant of βAa/b showed normal folliculogenesis in young females; however, their double mutant (inhbaa-/-;inhbab-/-) showed delayed follicle activation, granulosa cell hypertrophy, stromal cell accumulation and tissue fibrosis. The ovary of inhbaa-/- deteriorated progressively after 180 dpf with reduced fecundity and the folliculogenesis ceased completely around 540 dpf. In addition, tumor- or cyst-like tissues started to appear in the inhbaa-/- ovary after about one year. In contrast to females, activin βAa/b mutant males showed normal spermatogenesis and fertility. As for activin βB subunit, the inhbb-/- mutant exhibited normal folliculogenesis, spermatogenesis and fertility in both sexes; however, the fecundity of mutant females decreased dramatically at 270 dpf with accumulation of early follicles. In summary, the activin-inhibin system plays an indispensable role in fish reproduction, in particular folliculogenesis and ovarian homeostasis. Author summary: Activin and inhibin are important growth factors that play essential roles in animal development and reproduction. Activin and inhibin share the same β subunits, but they are antagonistic in function. Using gene editing technology, we studied the functional roles and importance of all three β subunits (βAs: inhbaa and inhbab; βB: inhbb) in zebrafish development and reproduction. Our results showed that the loss of all three subunits resulted in early death in zebrafish larvae, indicating functional importance of these molecules in development. Further analysis demonstrated essential roles of the β subunits especially βΑs (inhbaa and inhbab) in controlling female follicle development in the ovary. The loss of βΑs especially inhbaa showed delayed follicle activation and ovarian fibrosis. Without inhbaa gene, the ovary deteriorated progressively after 6 months and the formation of eggs stopped completely after 18 months. In summary, the present study provided comprehensive evidence for the relative importance of each β subunit in zebrafish reproduction. [ABSTRACT FROM AUTHOR]

The TGF-β superfamily members, activins and inhibins, are mainly involved in cell proliferation, cell survival, invasion, immune surveillance, and lesion growth in endometriosis. Herein, we investigated the modulation of the TGF-β type III receptor (betaglycan or BG) by activin A and inhibin A in endometriosis in vitro. Often, BG undergoes ectodomain shedding releasing soluble BG (sBG) which frequently antagonizes TGF-β signaling. The effects of activin A on BG shedding and signaling pathways involved were evaluated with the inhibitors LY364947 and SIS3, siRNA knockdown in human endometrial cells (12Z, THESC, Ishikawa, and primary stromal cells) and were quantified with BG ELISAs. The effects of activin A and inhibin A on the secretion of MMP2 and MMP3 were analyzed using ELISAs. The effects of activin A on the BG expression were analyzed using RT-qPCR and western blot. The CCK-8 and BrdU assays were used to evaluate the effects of the recombinant BG on cell viability and proliferation. Activin A stimulation resulted in a significant time- and dose-dependent reduction in BG shedding, which was found to be activin A/ALK-4/SMAD3- but not SMAD2-dependent. Activin A increased the BG mRNA expression but had no effect on the protein expression. Likewise, inhibin A was found to block BG shedding. Activin A, but not inhibin A, significantly enhanced the secretion of MMP2 and MMP3. The recombinant BG had no effect on the viability and proliferation of endometriotic cells. Together, these observations support a novel role for activin A with BG in modulating the TGF-β superfamily ligands in endometrial cells in vitro. [ABSTRACT FROM AUTHOR]

Congenital hypogonadotropic hypogonadism (CHH) is a rare disease caused by deficiency or action of gonadotropin‐releasing hormone. While generally considered a long‐life condition, CHH can be reversible in about 5%–20% of cases, but mechanisms of reversibility are unknown. We report the case of a male with CHH who began treatment with low dose (20 mg/day) transdermal testosterone to induce pubertal development at age 17. Following the start of treatment, he experienced testicular growth and his serum testosterone concentrations increased beyond the expectations in relation to the dose. Treatment was withdrawn, but this led to the reappearance of symptoms of hypogonadism and a drop in testosterone levels. Testosterone was again prescribed at the same dose and, for the subsequent years, he completed full puberty, including attainment of 20 cc testicular volume, mature secondary sexual characteristics, normal levels of testosterone and only partially arrested germinal function, as demonstrated by inhibin B levels and spermogram. Testosterone treatment was withdrawn three more times, but hypogonadism resumed on each occasion. This case suggests that low‐dose testosterone treatment can induce reversal of CHH through the activation, albeit non‐permanent, of the hypothalamic–pituitary–gonadal axis, indicating that testosterone administration might be a reliable therapeutic option for reverting GnRH deficiency. [ABSTRACT FROM AUTHOR]

This study evaluated the quality of fresh and frozen semen of Bali cattle and its correlation with the molecular weight (MW) of seminal plasma protein. This study collected semen from 10 bulls aged 5-10 years using an artificial vagina and evaluated the samples macroscopically and microscopically. Two batches of frozen semen obtained in 2020 and 2021 were also analyzed. The frozen semen samples were thawed at 37 °C for 30 seconds. The sperm motility, viability, intact plasma membrane (IPM), and sperm abnormalities were investigated. The concentration of the seminal plasma proteins was determined using the Bradford method, and the proteins were characterized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D-SDS-PAGE). Additionally, the gels were stained with Coomassie brilliant blue, and the MWs of the proteins were determined using MW markers. The sperm motility, viability, and abnormalities of fresh semen varied significantly among the bulls (p<0.05); however, sperm IPMs among the bulls were similar (p>0.05). No differences in sperm motility after freezing were found among the bulls. However, the sperm viability, abnormality, and IPM varied among the bulls. Meanwhile, the seminal plasma proteins contained bands with different MWs. No difference in the expression of protein bands between bulls. Linearity analysis showed that sperm motility (r= 0.281), viability (r= 0.189), abnormalities (r= 0.141), and IPM (r= 0.173) were positively correlated with the protein bands at each MW (p<0.05). The results conclude there was a positive correlation between the MW of the protein marker and the same protein expression levels in Bali bulls. Therefore, the band intensity of Bali cattle seminal plasma proteins can be used as a biomarker for selecting superior Bali bulls. [ABSTRACT FROM AUTHOR]

Context: Although Dolichandrone serrulata (Wall. ex DC.) Seem (Bignoniaceae) flower (DSF) improves hyperglycaemia, testicular damage and sperm quality in type 2 diabetes mellitus (T2DM) animals, its effects on the seminal vesicles, secreting seminal plasma, are unknown. Objective: This study reports the protective effects of DSF on seminal dysfunction in T2DM rats. Materials and methods: Male Sprague-Dawley rats were divided into four groups (control, T2DM, T2DMþDSF200 and T2DMþDSF600; 10 animals/group). The control group was fed a low-fat diet for 14 days prior to single saline injection, whereas T2DM group was given a high-fat diet and injected with streptozocin (50 mg/kg body weight). The T2DM-induced rats were fed DSF orogastrically (200 and 600mg/kg body weight) for 28 consecutive days. At the end of the experiment, biochemical components, malondialdehyde (MDA), histology and protein expression in seminal lysate were evaluated. Results: DSF increased the levels of serum phosphorus (13.66 ± 0.59mg/dL), ALP (11.85 ± 0.99U/L), GOT (3938.23 ± 251.41 U/L) and GPT (34.16 ± 4.93), decreased MDA levels in seminal tissue, and elevated the serum testosterone in the T2DM rats. Treatment with DSF ameliorated histological damage, significantly increased seminal 44 and 31 kDa TyrPho protein expression, and decreased that of caspase 3 and 9. Conclusions: DSF extract was able to mitigate seminal dysfunction in T2DM rats via improvements of tyrosine phosphorylation, testosterone level and biochemical substances, as well as reductions of caspase proteins. DSF may be developed as an alternative medicine in treating of T2DM male subfertility and progressive complications. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the potential mitigating effect of fisetin on monosodium glutamate (MSG)-induced testicular toxicity and investigate the possible involvement of silent mating type information regulation 2 homolog 1 (SIRT1) in this effect. Forty male rats were divided into normal control, fisetin-treated, MSG-treated, and fisetin + MSG-treated groups. Testosterone, GnRH, FSH, and LH were measured in plasma, as well as SIRT1 and phosphorylated AMP-activated protein kinase (pAMPK) levels in testicular tissues using ELISA. Hydrogen peroxide (H2O2), nitric oxide (NO), and reduced glutathione (GSH) were measured colorimetrically, while Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) expression was relatively quantified using RT–PCR in testicular tissues. After 30 days, fisetin could ameliorate MSG-induced testicular toxicity by acting centrally on the hypothalamic-pituitary-gonadal axis, increasing plasma levels of GnRH, FSH, LH, and testosterone. Peripheral actions of fisetin on the testis were indicated as it increased testicular SIRT1 and pAMPK. Furthermore, it antagonized glutamate-induced oxidative stress by significantly lowering H2O2, NO, and relative NOX4 expression while significantly increasing reduced GSH levels. It also improved the architecture of the seminiferous tubules, reduced sperm abnormality, and increased sperm count. Fisetin ameliorates MSG-induced testicular toxicity via central and peripheral mechanisms making it a promising therapeutic target for male infertility. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Follicular reconstruction and neo-oogenesis in xenotransplantation of human ovarian isolated cells derived from chemotherapy-induced POF patients" published in the Journal of Biological Engineering. The correction addresses an error in the caption of Figure 4, where "IHC" should be corrected to "ICC." The corrected caption describes the ICC analysis of various cells in the HOCCs isolated from transsexual and chemotherapy-induced POF ovaries. The original article has been corrected. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. [Extracted from the article]

Menopause causes important bodily and metabolic changes, which favor the increased occurrence of cardiovascular diseases, obesity, diabetes, and osteoporosis. Resveratrol exerts proven effects on body metabolism, improving glucose and lipid homeostasis and reducing inflammation and oxidative stress in various organs and tissues. Accordingly, this study evaluates the effects of resveratrol supplementation on the expression of markers associated with thermogenesis in brown adipose tissue, and on the body, metabolic and hormonal parameters of female mice submitted to bilateral oophorectomy. Eighteen female mice were randomized into three groups: G1: control (CONTROL), G2: oophorectomy (OOF), and G3: oophorectomy + resveratrol (OOF + RSV); the animals were kept under treatment for twelve weeks, being fed a standard diet and treated with resveratrol via gavage. Body, biochemical, hormonal, and histological parameters were measured; in addition to the expression of markers associated with thermogenesis in brown adipose tissue. The results showed that animals supplemented with resveratrol showed reduced body weight and visceral adiposity, in addition to glucose, total cholesterol, and triglyceride levels; decreased serum FSH levels and increased estrogen levels were observed compared to the OOF group and mRNA expression of PRDM16, UCP1, and SIRT3 in brown adipose tissue. The findings of this study suggest the important role of resveratrol in terms of improving body, metabolic, and hormonal parameters, as well as modulating markers associated with thermogenesis in brown adipose tissue of female mice submitted to oophorectomy. [Display omitted] • Resveratrol decreases weight and adiposty and provided improves glycemic and lipidhomeostasis in menopausal mice. • Resveratrol increasesestrogen levels and decreased FSH in menopausal mice. • Resveratrol increases the expression of UCP1, SIRT3, and PRDM16 in brown adipose tissue in menopausal mice.. [ABSTRACT FROM AUTHOR]

Testicular toxicity is a complication of cisplatin therapy and it limits its use. Since cisplatin-induced testicular damage is mediated by inflammation and oxidative stress, evaluation of the protective role of antioxidant and anti-inflammatory molecules such as micronized purified flavonoid fraction (Daflon®) is pertinent. Aim: Therefore, this study investigated the mitigating effect of daflon against cisplatin-induced testicular toxicity. Also, the impact of daflon on Nrf2/HO-1 and TLR4/NF-kB pathways, which are key pathways in cisplatin toxicity, was explored. Materials and methods: After 2 weeks of acclimatization, 20 male albino Wistar rats were allotted at random into 4 equal groups; control, daflon-treated, cisplatin-treated, and cisplatin+daflon-treated. Results: Daflon significantly restored cisplatin-induced reductions in body weight (112.20±9.01 vs. 129.60±5.68, P = 0.0175), body weight gain (-39.80±9.52 vs. −16.80±16.53, P = 0.0154), and testicular weight (1.69±0.08 vs. 1.95±0.13, P = 0.0980) and alterations in testicular histology. In addition, daflon abrogated cisplatin-induced rise in testicular CK (55.53±2.77 vs. 37.40±3.29, P< 0.0001) and LDH (74.52±3.20 vs. 65.89±2.08, P = 0.0009) activities, and lactate content (180.50±4.19 vs. 166.20±2.78, P < 0.0001). Also, daflon alleviated cisplatin-induced suppression of GnRH (5.09±0.60 vs. 10.17±0.51, P < 0.0001), LH (1.33±0.07 vs. 2.77±0.13, P < 0.0001), FSH (0.51±0.10 vs. 1.82±0.09, P < 0.0001), and testosterone (2.39±0.11 vs. 4.70±0.33, P < 0.001) as well as lowered sperm quality. More so, daflon attenuated cisplatin-induced testicular oxidative stress, inflammation, and apoptosis evidenced by daflon-driven suppression of MDA (14.16±0.66 vs. 9.22±0.52, P < 0.0001), TNF-α (79.42±5.66 vs. 54.13±3.56, P < 0.0001), IL-1β (8.63±0.41 vs. 3.37±0.43, P < 0.0001), IL-6 (6.87±0.48 vs. 3.67±0.32, P < 0.0001), and caspase 3 activity (4.20±0.26 vs. 0.72±0.23, P < 0.0001) and DNA fragmentation (34.60±3.05 vs. 17.20±3.19, P < 0.0001), and upregulation of GSH level (0.07±0.03 vs. 0.36±0.03, P < 0.0001), and GPx (5.96±0.46 vs. 11.88±1.05, P < 0.0001), GST (5.16±0.71 vs. 11.50±0.81, P < 0.0001), SOD (1.29±0.15 vs. 2.81±0.29, P < 0.0001), and catalase activities (6.18±0.69 vs. 10.71±0.74, P < 0.0001). Furthermore, daflon upregulated testicular Nrf2 expression (40.25±2.65 vs. 66.62±4.01, P < 0.0001) and HO-1 (4.18±0.56 vs. 8.79±0.55, P < 0.0001) activity but downregulated TLR4 (11.63±0.89 vs. 7.23±0.43, P < 0.0001) and NF-kB levels (113.20±3.36 vs. 78.22±3.90, P < 0.0001) in cisplatin-treated rats. Conclusion: Collectively, the ameliorative effect of daflon on cisplatin-induced testicular toxicity is associated with inhibition of oxidative stress and TLR4/NF-kB-mediated inflammatory pathways and activation of Nrf2/HO-1 signaling. [Display omitted] • Daflon prevented cisplatin-induced alterations in testicular histology. • Daflon ameliorated cisplatin-induced suppression HPT axis and sperm quality. • Daflon attenuated cisplatin-induced oxidative stress, inflammation, and apoptosis. • Daflon modulated Nrf2/HO-1 and TLR4/NF-kB signaling pathways. [ABSTRACT FROM AUTHOR]

We previously screened 6 differentially expressed miRNAs in ovarian tissues of 4-vinylcyclohexene diepoxide (VCD)-treated premature ovarian failure (POF) model in SD rats, including miRNA-190a-5p, miRNA-98-5p, miRNA-29a-3p, miRNA-144-5p,miRNA-27b-3p,miRNA-151-5p. In this study, to investigate the mechanisms causing the onset of POF, we first identified miRNAs with earlier differential expression at consecutive time points in the VCD-treated rat POF model and explored the mechanisms by which the target miRNAs promote POF. The SD ratswere injectedwith VCD for 15 days to induce POF. Additionally, we collected rat blood and ovaries at the same time every day for 15 consecutive days, and luteinizing hormone (LH), follicle-stimulating hormone (FSH), Anti-Mullerian hormone (AMH), and estradiol (E2) serum levels were detected by ELISA. Six miRNAs expression were measured in rat ovaries by qRT-PCR. Dual-luciferase reporter gene assays were employed to predict and verify the target gene (PHLPP1) of targetmiRNAs (miRNA-190a-5p). Western blot was examined to detect the expression levels of PHLPP1, AKT, p-AKT, FOXO3a, p-FOXO3a, and LHR proteins on the target gene PHLPP1 and its participation in the primordial follicular hyperactivation-related pathways (AKT-FOXO3a and AKT-LH/LHR). During the VCD modeling POF rat ovaries, miRNA-190a-5p was the first to show significant differential expression, i.e., 6th of VCD treating, and PHLPP1 was verified to be a direct downstream target of it. Starting from the 6th of VCD treatment, the more significant the up-regulation trend of miRNA-190a-5p expression, the more obvious the down-regulation trend of PHLPP1 and LHR mRNA and protein expression, accompanied by the more severe phosphorylation of AKT and FOXO3a proteins, thus continuously over-activating the rat primordial follicle to promote the development of POF. In conclusion, miRNA-190a-5p may become a potential biomarker for early screening of POF, and it can continuously activate primordial follicles in rats by targeting the expression of PHLPP1 and key proteins in the AKT-FOXO3a and AKT-LH/LHR pathways. [ABSTRACT FROM AUTHOR]

Pituitary gonadotropins directly govern ovarian functions, which are in turn regulated by the ovarian steroid hormones. The precise interplay of gonadotropins and steroid hormones is critical for follicle growth and differentiation. Furthermore, autophagy regulates ovarian follicle differentiation. However, how the high-fat-high fructose (HFD-HF) diet regulates gonadotropins and facilitates autophagy-mediated follicular differentiation in the ovary is obscure. We fed prepubertal rats (PND 25) an HFD-HF diet until PND 90. The results showed diminished adenohypophyseal GnRHR, PR, and aromatase expression, whereas AR, ERα, PRLR, and inhibin were augmented, resulting in gonadotropins decline. Interestingly, autophagy biomarkers, Beclin-1, ATG5, ATG12, LC3-II, and LAMP1 were reduced but SQSTM1/p62 was augmented in the ovaries of HFD-HF-fed rats, causing autolysosome to aggregation. The diet altered T, E2, P4, PRL, and their receptors status in the ovary, disturbed estrous cyclicity, and delayed vaginal opening. Ovarian histomorphology exhibited numerous cystic and atretic follicles, along with disturbed follicular maturation and ovulation. Moreover, the reduction of FSHR; steroidogenic proteins; receptor proteins AR, ERβ, PR; and signaling proteins Wnt2 and β-catenin was also noticed in the ovary, whereas PRLR, inhibin, and pGSK3β were augmented. In conclusion, exposure to a prepubertal HFD-HF diet leads to hypogonadotropism and the autophagy-mediated defective differentiation of ovarian follicles, abating fertility in adult rats. [ABSTRACT FROM AUTHOR]

Granulosa cell tumors (GCTs) are common ovarian neoplasms in the mare and bitch that can be challenging to diagnose on histopathology. Inhibin has long been the standard immunohistochemical (IHC) marker for GCTs; however, anti-Müllerian hormone (AMH) has not been evaluated widely as an IHC marker in the bitch and mare. We compared the efficacy of AMH and inhibin as IHC markers in canine and equine GCTs. We selected retrospectively 18 equine and 15 canine cases. All equine tumors were dominated by a cystic pattern; canine tumors often had solid patterns. Both inhibin and AMH had similar punctate cytoplasmic patterns of immunolabeling, although labeling intensity was variable; distribution and intensity of labeling were unrelated to the histomorphologic pattern. Labeling for AMH occurred in 12 of 15 canine and 18 of 18 equine cases. Labeling for inhibin occurred in 15 of 15 canine and 18 of 18 equine cases. AMH in equine GCTs often had stronger immunolabeling than inhibin, and granulosa cells were labeled more extensively. Inhibin and AMH performed comparably in bitches, but AMH had more diffuse immunolabeling than inhibin in mares. [ABSTRACT FROM AUTHOR]

The effects of Bifidobacterium sp., Clostridium butyricum, and Lactobacillus plantarum on the clinical symptoms of letrozole-induced polycystic ovary syndrome (PCOS) in rats were investigated. During the experiment, the estrus cycle, visceral fat mass and weight, Lee's index, and fasting plasma glucose levels were monitored. Thereafter, all the PCOS rats were sacrificed and the histological and fibrotic changes in ovarian tissue were observed using hematoxylin-eosin and Masson staining assays. The serum levels of sex hormones, blood lipids, insulin, and lipopolysaccharide were determined by enzyme-linked immunosorbent assay. The expression of key signaling molecules of the TGF-β/Smad signaling pathway, including Smad2, p-Smad2, Smad3, p-Smad3, and Smad4, in the rat ovaries was detected using western blots. Bifidobacterium sp., C. butyricum, and L. plantarum effectively restored the estrous cycle and improved insulin resistance. They significantly modulated the levels of sex hormones (T: 48.49, 45.71, and 40.36 nmol/L; E2: 46.63, 42.94, and 49.94 ng/L; FSH: 15.94, 17.77, and 18.73 IU/L; LH: 18.73, 18.94, and 17.27 ng/L), dyslipidemia (TG: 0.59, 0.69, and 0.79 mmol/L; TC: 4.65, 4.72, and 4.48 mmol/L; LDL-C: 0.40, 0.42, and 0.44 mmol/L; HDL-C: 1.99, 1.53, and 1.39 mmol/L), and LPS (102.62, 152.8, and 136.58 EU/L). Moreover, the intervention by all three probiotics significantly inhibited the expression of Smad4 (52.89%, 29.14%, and 69.80%), p-Smad3 (65.31%, 65.82%, and 78.57%), and p-Smad2 (77.42%, 52.86%, and 56.96%) (p<0.05). Hence, Bifidobacterium sp., C. butyricum, and L. plantarum exert significant protective effects on letrozole-induced PCOS in rats. [ABSTRACT FROM AUTHOR]

The inhibins control reproduction by suppressing follicle-stimulating hormone synthesis in pituitary gonadotrope cells. The newly discovered inhibin B coreceptor, TGFBR3L, is selectively and highly expressed in gonadotropes in both mice and humans. Here, we describe our initial characterization of mechanisms controlling cell-specific Tgfbr3l/TGFBR3L transcription. We identified two steroidogenic factor 1 (SF-1 or NR5A1) cis -elements in the proximal Tgfbr3l promoter in mice. SF-1 induction of murine Tgfbr3l promoter–reporter activity was inhibited by mutations in one or both sites in heterologous cells. In homologous cells, mutation of these cis -elements or depletion of endogenous SF-1 similarly decreased reporter activity. We observed nearly identical results when using a human TGFBR3L promoter–reporter. The Tgfbr3l gene was tightly compacted and Tgfbr3l mRNA expression was essentially absent in gonadotropes of SF-1 (Nr5a1) conditional knockout mice. During murine embryonic development, Tgfbr3l precedes Nr5a1 expression, though the two transcripts are fully colocalized by embryonic day 18.5 and thereafter. Collectively, these data indicate that SF-1 directly regulates Tgfbr3l/TGFBR3L transcription and is required for postnatal expression of the gene in gonadotropes. [ABSTRACT FROM AUTHOR]

We present a case of solid-tubulocystic variant of intrahepatic cholangiocarcinoma (also called cholangioblastic variant of intrahepatic cholangiocarcinoma) in a 15-year-old girl, the youngest patient reported to date. The tumor was located in the left lobe of the liver, predominantly solid with cystic areas, and measured 16 cm in greatest dimension. Microscopic examination showed 2 major histologic patterns: a mixed pattern with solid, tubulocystic, macrocystic, trabecular, and nested growth, diffuse cytokeratin 7/19 and weak neuroendocrine immunoreactivity, and low Ki-67 index; and a more compact, macrotrabecular/gyriform pattern with focal CK7/19, stronger neuroendocrine reactivity, and higher Ki-67 index. Inhibin immunoreactivity was diffuse throughout both patterns. Treatment included tumor resection with negative margins and 8 cycles of capecitabine chemotherapy; the patient is alive with no evidence of tumor 2.5 years after resection. Although molecular characterization of the tumor at the time of resection was unrevealing, a recent study has identified a novel NIPBL-NACC1 fusion transcript in this tumor type, which we have confirmed in this case. This case expands the reported age range of this rare tumor type and confirms a recently-reported diagnostic genomic alteration. Awareness of this rare entity affecting pediatric patients is crucial to avoid confusion with similar-appearing neoplasms. [ABSTRACT FROM AUTHOR]

Pharmacological and genetic studies over the past decade have established the follicle-stimulating hormone (FSH) as an actionable target for diseases affecting millions, namely osteoporosis, obesity, and Alzheimer's disease. Blocking FSH action prevents bone loss, fat gain, and neurodegeneration in mice. We recently developed a first-in-class, humanized, epitope-specific FSH-blocking antibody, MS-Hu6, with a KD of 7.52 nM. Using a Good Laboratory Practice (GLP)-compliant platform, we now report the efficacy of MS-Hu6 in preventing and treating osteoporosis in mice and parameters of acute safety in monkeys. Biodistribution studies using 89Zr-labeled, biotinylated or unconjugated MS-Hu6 in mice and monkeys showed localization to bone and bone marrow. The MS-Hu6 displayed a β phase t½ of 7.5 days (180 hr) in humanized Tg32 mice. We tested 217 variations of excipients using the protein thermal shift assay to generate a final formulation that rendered MS-Hu6 stable in solution upon freeze-thaw and at different temperatures, with minimal aggregation, and without self-, cross-, or hydrophobic interactions or appreciable binding to relevant human antigens. The MS-Hu6 showed the same level of "humanness" as human IgG1 in silico and was non-immunogenic in ELISpot assays for IL-2 and IFN-γ in human peripheral blood mononuclear cell cultures. We conclude that MS-Hu6 is efficacious, durable, and manufacturable, and is therefore poised for future human testing. [ABSTRACT FROM AUTHOR]

Objective: To see how letrozole and gonadotropin alter the levels of serum glycoproteins (HRG, AMH, and Inhibin B). Methods: As a control group, 33 infertile women and 22 healthy (fertile women) were recruited from an outpatient women's clinic (OWC). They are between the ages of (50) and (44). HRG, inhibin B, and AMH glycoproteins were evaluated using the ELISA technique. Results: According to a research that evaluated the blood levels of inhibin B, AMH, and HRG in infertile and healthy women, Infertile women's serum inhibin B levels are substantially lower than healthy women's (p = 0.05). Despite the fact that HRG and AMH concentrations were not significantly different (p > 0.05), the quantity and size of oocytes increased significantly (p = 0.000) in both the right and left ovarian infertile women after therapy as compared to the infertile ladies who were infertile before therapy. Conclusion: Letrozole and gonadotropin medicines have an effect on HRG and AMH levels in infertile women after treatment. [ABSTRACT FROM AUTHOR]

Obesity is linked to reproductive disorders. Novel neuropeptide phoenixin demonstrated many therapeutic actions. In this study, we aim to evaluate phoenixin's potential effect in obesity-induced infertility through modulating mitochondrial dynamics. Ninety adult female rats were divided to 4 groups: (I), fed with normal pellet diet; (II), given phoenixin; (III), fed with high-fat diet. Rats that developed obesity and infertility were divided to 2 groups: (III-A), received no further treatment; (III-B), given phoenixin. Our results showed that phoenixin treatment in obese infertile rats significantly decreased serum levels of insulin and testosterone and ovarian levels of dynamin-related protein1(Drp1),reactive oxygen species ROS, TNF-α, MDA, and caspase-3. Phoenixin treatment also significantly increased serum estrogen progesterone, LH, and FSH together with ovarian levels of GnRH receptor (GnRHR), mitofusin2(Mfn2), mitochondrial transmembrane potential (ΔΨm), and electron transport chain (ETC) complex-I significantly when compared with obese group. Ovarian histopathological changes were similarly improved by phoenixin. Our data demonstrate phoenixin's role in improving obesity-induced infertility. [ABSTRACT FROM AUTHOR]

Background: Recent epidemiological data suggest that Co-ronavirus disease 2019 (COVID-19) has a gender predisposition, with men being more seriously affected than women. Furthermore, older men accounting for most deaths. Therefore, this study aimed to investigate the serum testosterone, inhibin B, intrleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a) levels in different age groups of Jordanian males with SARS-CoV2 infection and to evaluate the correlation of these markers in male patients with COVID-19. Methods: This study was performed on 157 selected individuals divided into two groups; COVID-19 patients and healthy controls. The participants of each group were further divided into two subgroups based on the age (20-50 years and 51-80 years age groups). The biochemical tests that were performed in this research are testosterone, inhibin-B, TNF-α, and IL-6. Results: The levels of IL-6 were significantly higher in COVID-19 patients than healthy individuals (7.63 ± 6.30 vs. 5.54 ± 2.10, P=0.006). Similarly, the difference between the levels of TNF-α in the study groups were statistically significant (P=0.001). The mean testosterone levels in COVID-19 patients and healthy controls were 1.53 ± 1.24 and 3.87 ± 1.44, respectively (P<0.001), whereas the mean inhibin B levels in COVID-19 patients (54.29 ± 7.33) were lower than in healthy controls (64.14 ± 37.66) with P = 0.011. TNF-α was significantly and positively correlated with age (r = 0.263, P=0.018) and IL-6 (r = 0.245, P=0.027). Inhibin B had a significant, but negative correlation with TNF-α (r = -0.326, P = 0.003). Conclusions: It can be concluded that most men seeking medical attention with symptomatic COVID-19 had low testosterone and inhibin B levels with increased both IL-6 and TNF-α, which are independent of age conforming the deleterious effects of SARS-CoV-2 infection on testicular function and immune response induction. [ABSTRACT FROM AUTHOR]

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As a result of its expression in corresponding normal cell types, inhibin alpha (INHA) is used as an immunohistochemical marker for adrenocortical neoplasms and testicular or ovarian sex cord stromal tumors. However, other tumors can also express INHA. To comprehensively determine INHA expression in cancer, a tissue microarray containing 15,012 samples from 134 different tumor types and subtypes was analyzed by immunohistochemistry. INHA positivity was found in 72 of 134 tumor categories, including 26 categories with ≥1 strongly positive case. A moderate to strong INHA positivity was found in 100% of 37 granulosa cell tumors of the ovary, 100% of 43 other sex cord stromal tumors of the ovary/testis, 100% of 31 granular cell tumors, 78.5% of 28 adenomas, 44% of 25 carcinomas of the adrenal cortex, and 46.7% of 15 pancreatic acinar cell carcinomas. At least a weak INHA positivity was seen in <33% of cases of 46 additional tumor entities. In summary, these data support the use of INHA antibodies for detecting sex cord stromal tumors, granular cell tumors, and adrenocortical neoplasms. Since INHA can also be found in other tumor entities, INHA immunohistochemistry should only be considered as a part of any panel for the distinction of tumor entities. [ABSTRACT FROM AUTHOR]

Testosterone is a hormone that plays a key role in carbohydrate, fat, and protein metabolism. Testosterone deficiency is associated with multiple comorbidities, e.g., metabolic syndrome and type 2 diabetes. Despite its importance in many metabolic pathways, the mechanisms by which it controls metabolism are not fully understood. The present study investigated the short-term metabolic changes of pharmacologically induced castration and, subsequently, testosterone supplementation in healthy young males. Thirty subjects were submitted to testosterone depletion (TD) followed by testosterone supplementation (TS). Plasma samples were collected three times corresponding to basal, low, and restored testosterone levels. An untargeted metabolomics study was performed by liquid chromatography–high resolution mass spectrometry (UHPLC–HRMS) to monitor the metabolic changes induced by the altered hormone levels. Our results demonstrated that TD was associated with major metabolic changes partially restored by TS. Carnitine and amino acid metabolism were the metabolic pathways most impacted by variations in testosterone. Furthermore, our results also indicated that LH and FSH might strongly alter the plasma levels of indoles and lipids, especially glycerophospholipids and sphingolipids. Our results demonstrated major metabolic changes induced by low testosterone that may be important for understanding the mechanisms behind the association of testosterone deficiency and its comorbidities. [ABSTRACT FROM AUTHOR]

Simple Summary: Early pregnancy regulation is an extremely complex process that is influenced by various factors. We previously mined the differentially expressed genes affected by N-acetyl-L-cysteine (NAC) in early pregnancy in goats via transcriptome sequencing. We found that NAC increased the number of lambs by affecting the immune pathway in ewes and enhancing antioxidation. Based on this, we here explored the effect of NAC on early pregnancy in goats at the protein level. The results showed a difference in the expression of uterine keratin and increases in the levels of antioxidant indices and hormones in doe serum. Dietary supplementation with N-acetyl-L-cysteine (NAC) may support early pregnancy regulation and fertility in female animals. The purpose of this study was to investigate the effect of supplementation with 0.07% NAC on the expression of the uterine keratin gene and protein in Qianbei-pockmarked goats during early pregnancy using tandem mass spectrometry (TMT) relative quantitative proteomics. The results showed that there were significant differences in uterine keratin expression between the experimental group (NAC group) and the control group on day 35 of gestation. A total of 6271 proteins were identified, 6258 of which were quantified by mass spectrometry. There were 125 differentially expressed proteins (DEPs), including 47 upregulated and 78 downregulated proteins, in the NAC group. Bioinformatic analysis showed that these DEPs were mainly involved in the transport and biosynthesis of organic matter and were related to the binding of transition metal ions, DNA and proteins and the catalytic activity of enzymes. They were enriched in the Jak-STAT signalling pathway, RNA monitoring pathway, amino acid biosynthesis, steroid biosynthesis and other pathways that may affect the early pregnancy status of does through different pathways and thus influence early embryonic development. Immunohistochemistry, real-time quantitative PCR and Western blotting were used to verify the expression and localization of glial fibrillary acidic protein (GFAP) and pelota mRNA surveillance and ribosomal rescue factor (PELO) in uterine horn tissue. The results showed that both PELO and GFAP were localized to endometrial and stromal cells, consistent with the mass spectrometry data at the transcriptional and translational levels. Moreover, NAC supplementation increased the levels of the reproductive hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol (E2), progesterone (P4), superoxide dismutase (SOD), glutamate peroxidase (GSH-Px) and nitric oxide (NO) in the serum of does. These findings provide new insight into the mechanism by which NAC regulates early pregnancy and embryonic development in goats. [ABSTRACT FROM AUTHOR]

Purpose: Adenocarcinomas of the esophagus (AEG) and stomach (AS) are among the most common cancers worldwide. Novel markers for risk stratification and guiding treatment are strongly needed. Activin is a multi-functional cytokine with context specific pro- and anti-tumorigenic effects. We aimed to investigate the prognostic role of activin tumor protein expression in AEG/ASs.Methods: Tissue from a retrospective cohort of 277 patients with AEG/AS treated primarily by surgery at the Charité - Universitätsmedizin Berlin was collected and analyzed by immunohistochemistry using a specific antibody to the activin homodimer inhibin beta A. Additionally, we evaluated T-cell infiltration and PD1 expression as well as expression of PD-L1 by immunohistochemistry as possible confounding factors. Clinico-pathologic data were collected and correlated with activin protein expression.Results: Out of 277 tumor samples, 72 (26.0%) exhibited high activin subunit inhibin beta A protein expression. Higher expression was correlated with lower Union for International Cancer Control (UICC) stage and longer overall survival. Interestingly, activin subunit expression correlated with CD4+ T-cell infiltration, and the correlation with higher overall survival was exclusively seen in tumors with high CD4+ T-cell infiltration, pointing towards a role of activin in the tumor immune response in AEG/ASs.Conclusion: In our cohort of AEG/AS, higher activin subunit levels were correlated with longer overall survival, an effect exclusively seen in tumors with high CD4+ cell infiltration. Further mechanistic research is warranted discerning the exact effect of this context specific cytokine. [ABSTRACT FROM AUTHOR]

The progressive improvement of lymphoma treatment has led to an important prolongation of patient survival and life expectancy. The principal international scientific societies of oncology now therefore recommend that long-term survivors of lymphoma join fertility programs. Specifically, fertile-age patients should be assisted by a multidisciplinary team, including specialists dedicated to fertility preservation in oncology, in order to support the completion of their reproductive project. In the general population, the use of Myo-Inositol and D-Chiro-Inositol (MI/DCI) has been demonstrated to be an effective choice to treat ovarian dysfunctions, with a consequent improvement in reproductive outcomes, so it may represent an adjuvant strategy for this purpose. We therefore conducted a pilot prospective case–control study to evaluate the potentialities of this nutritional supplement, with the aim of optimizing reproductive function in female long-term survivors of lymphoma. One group underwent oral supplementation with MI 1200 mg and DCI 135 mg per day for 12 months, compared with controls who underwent no treatment in the same period. After 12 months, FSH, LH, and progesterone levels, as well as oligomenorrhea and antral follicle count (AFC), were significantly improved in the MI/DCI group. In addition, a significantly higher mean value in FSH and LH and a significantly lower mean AFC value in the right ovary were observed in controls compared to the MI/DCI group. Despite the need for further investigation, MI/DCI could be considered a potential adjuvant strategy to restore ovarian function in female long-term survivors of lymphoma. [ABSTRACT FROM AUTHOR]

Inhibin is a molecule that belongs to peptide hormones and is excreted through pituitary gonadotropins stimulation action on the granulosa cells of the ovaries. However, the differential regulation of inhibin and follicle-stimulating hormone (FSH) on granulosa cell tumor growth in mice inhibin-deficient females is not yet well understood. The objective of this study was to evaluate the role of inhibin and FSH on the granulosa cells of ovarian follicles at the premature antral stage. This study stimulated immature wild-type (WT) and Inhibin-α knockout (Inha−/−) female mice with human chorionic gonadotropin (hCG) and examined hCG-induced gene expression changes in granulosa cells. Also, screening of differentially expressed genes (DEGs) was performed in the two groups under study. In addition, related modules to external traits and key gene drivers were determined through Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm. The results identified a number of 1074 and 931 DEGs and 343 overlapping DEGs (ODEGs) were shared in the two groups. Some 341 ODEGs had high relevance and consistent expression direction, with a significant correlation coefficient (r2 = 0.9145). Additionally, the gene co-expression network of selected 153 genes showed 122 nodes enriched to 21 GO biological processes (BP) and reproduction and 3 genes related to genomic pathways. By using principal component analysis (PCA), the 14 genes in the regulatory network were fixed and the cumulative proportion of fitted top three principal components was 94.64%. In conclusion, this study revealed the novelty of using ODEGs for investigating the inhibin and FSH hormone pathways that might open the way toward gene therapy for granulosa cell tumors. Also, these genes could be used as biomarkers for tracking the changes in inhibin and FSH hormone from the changes in the nutrition pattern. [ABSTRACT FROM AUTHOR]

Objective: Mucuna pruriens Linn., a leguminous plant, is identified as a herbal medicine for improving fertility-related disorders in the alternative and complementary systems of medicine. The study was focused on evaluating the therapeutic potential of M. pruriens on testis and sperm parameters in a high-fat-induced hypercholesterolemia model. Materials and Methods: Male rats were divided as normal-control rats (NCR); normal-control rats + M.pruriens (200 mg/kg b.w. of ethanolic extract of M. pruriens seed) treated (NCRD); hypercholesterolemic rats (HCR) and hypercholesterolemic rats + M. pruriens (HCRD). Groups were further divided into three post-exposure periods (subgroups) of 9, 18, and 36 days, and the progressive changes in testis histology and sperm were analyzed. Results: The study showed a significant impairment in testicular histoarchitecture, depletion of antioxidant enzyme levels, increased oxidative stress and lipid peroxidation in the HCR group. The study indicated severe structural and functional damage in sperm parameters and diminished chromatin integrity in the HCR group. In the HCR rats, the follicular stimulating hormone (FSH) and luteinizing hormone (LH) and testosterone were significantly reduced. There was a significant improvement in sperm parameters and testis histology in the HCRD group. Conclusion: The study reveals the potential efficacy of M. pruriens to improve spermatogenesis, sperm parameters and hormone levels in hypercholesterolemic rats. [ABSTRACT FROM AUTHOR]

The objective of the present study was to evaluate the effects of a novel Inhibin (INH) DNA vaccine (C500/pVAX-asd-IS) on the immune response, reproductive hormone levels, and spermatogenesis of rats. Forty healthy male rats were divided into four groups, and respectively immunized (thrice, 14 d apart) with 1×10 8 , 1×10 9 , and 1×10 10 CFU of the recombinant inhibin vaccine (group C500/pVAX-asd-IS-L, C500/pVAX-asd-IS-M, and C500/pVAX-asd-IS-H) or 1×10 10 CFU C500. P/N values increased after vaccination and differed ( p <0.05) at 7 d, and sharply increased at 14 d following the booster vaccination ( p <0.01); The weight and volume of testes in C500/pVAX-asd-IS groups were increased ( p < 0.05) at decapitation, respectively; Histological evaluation showed that the number of spermatogenic cells in the lumen was increased, and the cytoplasmic remnants of sperms were allergy increased significantly compared with the control group. Oral vaccination with INH DNA reduced ( P < 0.05) serum concentrations of INH B, enhanced serum concentrations of testosterone (T) and FSH. Furthermore, mRNA expressions of VIM and SMAD4 in the testes were increased in C500/pVAX-asd-IS-M and C500/pVAX-asd-IS-H groups ( p < 0.05 or p < 0.01). The mRNA amount of INHβ-B in C500/pVAX-asd-IS-M group was greater than control group ( p < 0.05).These results suggested that neutralization of endogenous INH through oral vaccination with INH DNA delivered by C500 strain successfully elicited a humoral immune response. INH gene immunization may have a positive effect on spermatogenesis and reproductive efficiency in male rats., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare., (Copyright © The Author(s).)