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Reproductive success relies on proper establishment and maintenance of biological sex. In many animals, including mammals, the primary gonad is initially ovary biased. We previously showed the RNA binding protein (RNAbp), Rbpms2, is required for ovary fate in zebrafish. Here, we identified Rbpms2 targets in oocytes (Rbpms2-bound oocyte RNAs; rboRNAs). We identify Rbpms2 as a translational regulator of rboRNAs, which include testis factors and ribosome biogenesis factors. Further, genetic analyses indicate that Rbpms2 promotes nucleolar amplification via the mTorc1 signaling pathway, specifically through the mTorc1-activating Gap activity towards Rags 2 (Gator2) component, Missing oocyte (Mios). Cumulatively, our findings indicate that early gonocytes are in a dual poised, bipotential state in which Rbpms2 acts as a binary fate-switch. Specifically, Rbpms2 represses testis factors and promotes oocyte factors to promote oocyte progression through an essential Gator2-mediated checkpoint, thereby integrating regulation of sexual differentiation factors and nutritional availability pathways in zebrafish oogenesis.

Background: Finding an ovary and/or fallopian tube within an indirect inguinal hernia is a rare occurrence that can be detected incidentally during elective surgery or present as a medical emergency requiring immediate intervention. Hence, it poses a difficult clinical picture in a reproductive-age woman with groin mass. Clinical presentation: We describe the case of a 45-year-old Ethiopian woman of Amhara ethnicity who presented with a left inguinal swelling that persisted for 5 years. Physical examination revealed an irreducible, non-tender lump in the left groin and an ultrasonography scan confirmed the presence of an indirect inguinal hernia. The patient was then scheduled for elective hernia repair. During the surgery, both her left ovary and fallopian tube were found within the hernial sac. The contents were released from the sac, high ligation performed, and the inguinal floor repaired with mesh. Discussion: Inguinal hernias in women are rare and often present a diagnostic challenge. Although the exact pathogenesis of inguinal hernias containing female genital organs is unknown, some risk factors have been postulated. Diagnosis should start with a physical exam and imaging, but many of the cases have been intraoperative surprises. Management is primarily surgical, ranging from simple reduction and hernia repair to salpingo-oophorectomy depending on the status of the hernia contents. Conclusion: This report emphasizes the importance of maintaining a high index of suspicion when examining females with inguinal hernias to ensure accurate diagnosis and management of tubo-ovarian hernias. Although rare, inguinal hernias containing female genital organs should be considered in the differential diagnosis of inguinal hernias, as early detection and appropriate surgical management can prevent potential complications. [ABSTRACT FROM AUTHOR]

Yaks (Bos grunniens) exhibit exceptional adaptation to the challenging highaltitude environment of the Qinghai-Tibetan plateau, making them the sole bovine species capable of thriving in such exreme conditions. Investigating the cellular and molecular characteristics of yak ovaries across different reproductive states is crucial for gaining insight into their ovarian functions. Herein, the cellular atlases of yak ovaries in different reproductive states were depicted by single-cell RNA-sequencing (scRNA-seq). The cellular atlases of the ovaries were established by identifying specific gene expression patterns of various cell types, including granulosa cells, theca cells, stromal cells, smooth muscle cells, endothelial cells, glial cell, macrophages, natural killer cells, and proliferating cells. The cellular compositions of the ovaries vary among different reproductive states. Furthermore, the granulosa cells comprise six cell subtypes, while theca cells consist of eight cell subtypes. The granulosa cells and theca cells exhibit distinct biological functions throughout different reproductive states. The two cell types were aligned along their respective pseudotime trajectories. Moreover, a cell-to-cell communication network was constructed among distinct cell types within the ovary, spanning the three reproductive states. Notably, during the estrus period, the granulosa cells demonstrated more prominent interactions with other cell types compared to the remaining reproductive states. [ABSTRACT FROM AUTHOR]

Introduction: Survival rates of the childhood cancer patients are improving, however cancer treatments such as chemotherapy may lead to infertility due to loss of the primordial follicle (PMF) reserve. Doxorubicin (DXR) is a gonadotoxic chemotherapy agent commonly used in childhood cancers. Anti-Müllerian Hormone (AMH) has been reported to have a protective effect on the mouse ovarian reserve against DXR in vivo. However, whether AMH can prevent PMF loss in conjunction with DXR in human ovarian tissue in vivo has not been determined. Methods: In order to investigate this, we first established an optimum dose of DXR that induced PMF loss in cultured mouse ovaries and investigated the efficacy of AMH on reducing DXR-induced PMF loss in mice in vitro. Second, we investigated the effects of DXR on pre-pubertal human ovarian tissue and the ability of AMH to prevent DXR-induced damage comparing using a mouse xenograft model with different transplantation sites. Results: Mouse ovaries treated with DXR in vitro and in vivo had reduced PMF populations and damaged follicle health. We did not observe effect of DXR-induced PMF loss or damage to follicle/stromal health in human ovarian cortex, this might have been due to an insufficient dose or duration of DXR. Although AMH does not prevent DXR-induced PMF loss in pre-pubertal and adult mouse ovaries, in mouse ovaries treated with higher concentration of AMH in vitro, DXR did not cause a significant loss in PMFs. This is the first study to illustrate an effect of AMH on DXR-induced PMF loss on pre-pubertal mouse ovaries. However, more experiments with higher doses of AMH and larger sample size are needed to confirm this finding. Discussion: We did not observe that AMH could prevent DXR-induced PMF loss in mouse ovaries in vivo. Further studies are warranted to investigate whether AMH has a protective effect against DXR in xenotransplanted human ovarian tissue. Thus, to obtain robust evidence about the potential of AMH in fertility preservation during chemotherapy treatment, alternative AMH administration strategies need to be explored alongside DXR administration to fully interrogate the effect of DXR and AMH on human xenografted tissues. [ABSTRACT FROM AUTHOR]

Simple Summary: Genital tract disorders are among the most prevalent conditions affecting female pet rabbits (Oryctolagus cuniculus). However, ovarian diseases are relatively rare, constituting only 3.3% of reproductive conditions in this species. These may include ovarian cysts, neoplasia, and necrosis. This study presents the first documented case of spontaneous ovarian torsion in rabbits. A female pet rabbit presented for routine clinical examination exhibited a large abdominal mass, the nature of which remained ambiguous upon diagnostic imaging. Computed tomography revealed a mass exhibiting specific signs indicative of torsion of the supporting ligaments of the right ovary. Confirmation of the diagnosis was achieved during laparotomy, where twisting of the right ovarian pedicle was observed. The rabbit was neutered, and the mass underwent histological examination, revealing predominantly necrotic areas with no evidence of neoplastic cells. Ovarian torsion (OT) is a condition that can affect both humans and animals, although it is less common in the latter, with very few cases documented in the literature. To our knowledge, no previous reports have documented the occurrence of this condition in rabbits. In this study, we present the first documented case of spontaneous OT in a 2-year-old female intact rabbit. The patient was brought to the clinic for a routine check-up, during which a firm, large abdominal mass was palpated. Subsequent ultrasound examination of the abdomen revealed the presence of a large, hypoechoic, non-vascularized mass occupying the majority of the caudal abdomen. A computed tomography (CT) scan further confirmed the presence of a heterogeneous mass exhibiting the Whirlpool sign, which is characteristic of organ torsion. Upon laparotomy, an enlargement of the right ovary was observed, characterized by twisting of the ovarian pedicle, consistent with the mass detected via ultrasound and CT scan. Ovariohysterovaginectomy was performed, and the mass was subsequently analyzed. Microscopic analysis of the mass revealed predominantly necrotic tissue, with only a few ovarian epithelial cells present. The underlying cause of the OT described in this study remains unclear. However, it is plausible that a previous neoplastic condition or ovarian necrosis led to an increase in the size and weight of the mass, ultimately resulting in the twisting of the supporting structures. [ABSTRACT FROM AUTHOR]

Anastomosing hemangioma of the ovary is a rare vascular tumor that predominantly affects middle-aged women. Despite its benign nature, its histological appearance can mimic aggressive vascular lesions, posing diagnostic challenges. This review aims to provide an overview of this uncommon entity. The PubMed and Scopus databases were searched for relevant articles published in English. Information on all retrieved cases was extracted and reviewed in detail. We found 33 cases with relevant details of anastomosing heamangioma of the ovary. Despite the small number of cases we found, our study demonstrated the importance of an accurate hystopathological evaluation. Although the preliminary imaging and initial microscopic features may appear alarming, careful microscopic examination reveals benign behavior. There is a need to raise awareness of this unusual and rare entity to improve morphologic recognition and avoid misdiagnosis that could lead to unnecessary treatment or patient anxiety. [ABSTRACT FROM AUTHOR]

Background: Stathmin, a cytosolic microtubule-destabilizing phosphoprotein involved in the regulation of mitosis, is widely expressed in various malignancies and acts as an adverse prognostic factor. Our research analyzed its immunohistochemical expression on a large cohort of ovarian sex cord-stromal tumors, evaluating its potential utility in differential diagnosis, prognosis, and therapeutic application. Methods: We examined 390 cases of ovarian sex cord-stromal tumors including 281 adult granulosa cell tumors (AGCT), 5 juvenile granulosa cell tumors (JGCT), 33 Sertoli-Leydig cell tumors (SLCT), 50 fibromas/thecomas (F/T), 11 Leydig cell tumors/steroid cell tumors (LCT/SterCT), 5 sex-cord stromal tumors NOS (SCST-NOS), 3 Sertoli cell tumors (SCT), and 2 sclerosing stromal tumors (ScST). Immunohistochemical analysis was performed using TMAs. Results: Strong expression (> 50%) was observed in all cases of AGCT, JGCT, SLCT, SCST-NOS, SCT and 1 ScST. The other case of ScST exhibited mild expression (5–10%). The negative cases included exclusively F/T and LCT/SterCT, with F/T showing 24% of negative cases and LCT/SterCT comprising 64% of negative cases. Conclusion: The results of our study indicate that stathmin is neither a prognostic marker nor suitable for the differential diagnosis of challenging cases of ovarian sex cord-stromal tumors. However, its predictive value may be theoretically significant, as a decrease in stathmin expression potentialy influences response to chemotherapy treatment. [ABSTRACT FROM AUTHOR]

The idea of utilizing unused oocytes present in the ovaries has been tested in various ways to produce offspring. However, only a limited number of studies succeeded in offspring generation. They include transplantation of ovaries into autologous or allogeneic animals, and acquisition of pups from oocytes obtained by transplanting mouse ovaries into immunodeficient rats. Here we report successful production of rat oocytes by transplanting rat ovaries under the kidney capsule of immunodeficient mice with addition of hormone administration to the mice. In addition, these oocytes were developed by in vitro fertilization, and transplanted into the oviducts of pseudopregnant rats, resulting in successful delivery of pups. The modified gene of the donor rat was confirmed to be correctly inherited to the pups. These results show that xenotransplantation of ovarian tissue makes it possible to leave offspring, beginning a new phase in developmental engineering. [ABSTRACT FROM AUTHOR]

Objective: To compare the diagnostic effectiveness of the Gynecologic Imaging Reporting and Data System (GI-RADS) and Neoplasias in the Adnexa (ADNEX) model for the diagnosis of benign and malignant ovarian tumors by junior physicians. Methods: The sonographic data of 634 patients with ovarian tumors confirmed by pathology in our hospital over 4 years were analyzed retrospectively by junior doctors. The diagnostic efficacy of the GI-RADS and ADNEX models was compared based on pathology. Results: (1) Regarding the diagnostic efficacy of the GI-RADS and ADNEX models, the sensitivity was 90.15% and 84.85%, the specificity was 87.65% and 85.86%, the accuracy rates were 88.17% and 85.65%, and the Youden Indices were 0.778 and 0.707, respectively. The areas under the receiver operating characteristic (ROC) curves were 0.924 (95% CI: 0.900-0.943) and 0.933 (95% CI: 0.911-0.951), respectively. The GI-RADS classification was equivalent to that of the ADNEX model in the diagnosis of adnexal tumors (P>0.05). These findings were highly consistent with the pathological results (Kappa values were 0.684 and 0.691, respectively). (2) When differentiating between different pathological types of adnexal tumors, the ADNEX model had the best diagnostic value for distinguishing between benign tumors and stage II-IV ovarian cancer (AUC=0.990, 95% CI: 0.978-0.997). Conclusions: (1) The diagnostic efficacy of the GI-RADS and ADNEX models in the diagnosis of benign and malignant ovarian tumors by junior physicians is excellent and comparable. (2) The ADNEX model shows good value for differentiating ovarian tumors of different pathological types by junior physicians [ABSTRACT FROM AUTHOR]

A 27-year-old man was admitted to the hospital after a year of marriage due to infertility. During laparoscopic exploratory surgery, the presence of a retrovesical uterus was clearly observed, and the gonadal organs were visible on both sides. However, the testicles or ovaries were not identifiable, nor were the spermatic vessels and fallopian tubes at the joint. Intraoperative bilateral gonad biopsy was performed. Cryopreservation of the right gonadal gland revealed gonadoblastoma and malignant germinoma (asexual tumor/seminoma) with sclerosis and atrophy of testicular tissue. No proliferation of germ cells and sertoli cells was observed in spermatic tubule. The left gonad was diagnosed as a gonadoblastoma. Finally, total hysterectomy and bilateral gonadal tumor organectomy were performed to seal the vaginal stump. Local radiotherapy was administered after surgery. In general, tumors were found on both sides of the gonads, especially gonadoblastoma and malignant germinoma on the right side and gonadoblastoma on the left side. [ABSTRACT FROM AUTHOR]

Background: Secreted frizzled-related proteins (SFRPs) comprise a family of WNT signaling antagonists whose roles in the ovary are poorly understood. Sfrp4-null mice were previously found to be hyperfertile due to an enhanced granulosa cell response to gonadotropins, leading to decreased antral follicle atresia and enhanced ovulation rates. The present study aimed to elucidate the mechanisms whereby SFRP4 antagonizes FSH action. Methods: Primary cultures of granulosa cells from wild-type mice were treated with FSH and/or SFRP4, and effects of treatment on gene expression were evaluated by RT-qPCR and RNAseq. Bioinformatic analyses were conducted to analyse the effects of SFRP4 on the transcriptome, and compare them to those of FSH or a constitutively active mutant of FOXO1. Additional granulosa cell cultures from wild-type or Sfrp4-null mice, some pretreated with pharmacologic inhibitors of specific signaling effectors, were used to examine the effects of FSH and/or SFRP4 on signaling pathways, autophagy and apoptosis by western blotting and TUNEL. Results: Treatment of cultured granulosa cells with recombinant SFRP4 was found to decrease basal and FSH-stimulated mRNA levels of FSH target genes. Unexpectedly, this effect was found to occur neither via a canonical (CTNNB1-dependent) nor non-canonical WNT signaling mechanism, but was found to be GSK3β-dependent. Rather, SFRP4 was found to antognize AKT activity via a mechanism involving AMPK. This lead to the hypophosphorylation of FOXO1 and a decrease in the expression of a portion of the FSH and FOXO1 transcriptomes. Conversely, FSH-stimulated AMPK, AKT and FOXO1 phosphorylation levels were found to be increased in the granulosa cells of Sfrp4-null mice relative to wild-type controls. SFRP4 treatement of granulosa cells also induced autophagy by signaling via AKT-mTORC1-ULK1, as well as apoptosis. Conclusions: This study identifies a novel GSK3β-AMPK-AKT signaling mechanism through which SFPR4 antagonizes FSH action, and further identifies SFRP4 as a novel regulator of granulosa cell autophagy. These findings provide a mechanistic basis for the phenotypic changes previously observed in Sfrp4-null mice, and broaden our understanding of the physiological roles of WNT signaling processes in the ovary. [ABSTRACT FROM AUTHOR]

Simple Summary: Activin is a dimeric growth factor with diverse biological activities in vertebrates. This study aimed to investigate the regulatory role of the activin signaling pathway in the ovary of cultured Acipenser sinensis. One activinβA subunit with a full-length cDNA sequence of 1572 base pairs was identified. Multiple sequence alignment and phylogenetic analyses indicated the conserved evolution of ActivinβA from mammals to fish species. Transcripts of activinβA were distributed ubiquitously in ovary and non-ovarian tissues. The in vitro human recombinant Activin A incubation stimulated not only the activin system-related gene transcriptions of activinβA, follistatin, its receptors activinRIIA and activinRIIB, and smad2, smad3, and smad4, but also the ovary development-related genes cyp19a1a, erα, and erβ. Gonadotropin activated activin signaling by recruiting activinβA, follistatin, activinRIIA, and smad2. These results were helpful for not only the molecular exploration of activin signaling in fish species, but also the ovarian maturation regulation of A. sinensis. Activin is a dimeric growth factor with diverse biological activities in vertebrates. This study aimed to investigate the regulatory role of the activin signaling pathway in the ovary of the endangered, cultured sturgeon species Acipenser sinensis. One activinβA subunit was identified, with a full-length complementary DNA (cDNA) sequence of 1572 base pairs. Multiple sequence alignment suggested that ActivinβA shared high sequence identities with its counterparts in four other sturgeon species. Phylogenetic analysis indicated the conserved evolution of ActivinβA among vertebrates from mammals to fish species. Transcripts of activinβA were distributed ubiquitously in the liver, kidney, intestine, ovary, midbrain, hypothalamus, and pituitary, with the highest transcription found in the pituitary. In Chinese sturgeon ovarian cells, in vitro human recombinant Activin A incubation stimulated the activin system-related gene transcriptions of activinβA, follistatin, its receptors -activinRIIA and activinRIIB, and drosophila mothers against decapentaplegic proteins (smads) smad2, smad3, and smad4. Ovary development-related mRNA levels of cyp19a1a and aromatase receptors of erα and erβ were enhanced by Activin A or human chorionic gonadotropin (hCG) incubation. Furthermore, 15 IU/mL hCG treatment increased the transcription levels of activinβA, follistatin, activinRIIA, and smad2. This suggested that the activin system was functional for the regulation of ovary development in Chinese sturgeon, possibly under the regulation of gonadotropin, by recruiting activinβA, follistatin, activinRIIA, and smad2. These results were helpful for the molecular exploration of activin signaling in fish species, as well as the ovarian maturation regulation of A. sinensis. [ABSTRACT FROM AUTHOR]

Enclosed ovules are a reproductive feature restricted to angiosperms. Although this feature can be used as a criterion for identifying fossil angiosperms, how ovules are enclosed and the nature of the placenta are still foci of debates. A reason underlying these controversies is the lack of reproductive organ fossils shedding light on these issues. These controversies hinder a clear understanding of angiosperm evolution and systematics. Here, we report a new fossil ovary, Xenofructus dabuensis gen. et sp. nov, from the Middle Jurassic of Liaoning, China. Our fossil clearly demonstrates the existence of ovules in Xenofructus that has a free central placentation. This new feature implies that a placenta in angiosperm gynoecia is homologous to an ovule/seed-bearing axis, and free central placentation is one of the early developed placentations. This discovery is apparently at odds with the current understanding of placentation and its evolution. Apparently, the understanding of angiosperms and their gynoecia should be updated with newly available palaeobotanical data. [ABSTRACT FROM AUTHOR]

Introduction: The reproductive system is tightly regulated by environmental and physiological signals. Melatonin, known as the hormone of darkness, plays a crucial role in regulating both the circadian and reproductive systems in mammals. Hypothyroidism is a key endocrine disorder that harms the reproductive system. Despite many studies on melatonin's effects on the reproductive system, there is conflicting information regarding melatonin synthesis modulation in hypothyroidism. The objective of this study was to investigate the modulation of plasma melatonin levels and gene expression of Aanat and Asmt in the pineal gland and gonads of rats with hypothyroidism at different times of the day. Methods: Female and male Wistar rats were divided into control and hypothyroid groups. Hypothyroidism was induced using propylthiouracil (PTU) for 15 days, rats were euthanized six hours after lights on (ZT6), before lights off (ZT11.5), and six hours after lights off (ZT18). Free thyroxine (FT4) and melatonin were quantified in plasma, and gene expressions of melatonin synthesizing enzymes (Aanat and Asmt) were measured in pineal and sexual organs (testis and ovary). Also, morphological analysis was performed in sexual organs. Results: The results reveal some disparities between the sexes. Hypothyroidism reduced antral and primary follicles in the ovary, and reduced the weight of testis, epididymis, and prostate. In relation to gene expression, we observed a reduction in Aanat expression in the pineal gland during the light phase (ZT6), and in males, this reduction occurred during the dark phase (ZT18). Regarding Asmt expression, there was a decrease in females also during the dark phase (ZT18). In the gonads, there was an increase in expression in both sexes at ZT11.5. Additionally, it was interesting to observe the association between FT4 levels and Asmt expression in the gonads. Conclusions: This study showed that acute hypothyroidism can affect components of the melatonergic system in gonads, particularly gene expression of melatonin synthesis enzymes (Aanat and Asmt) contributing to changes in reproduction organs during disease progression. These findings enhance our understanding of melatonin synthesis in the reproductive system during hypothyroidism, showing distinct responses in male and female rats, and suggest that hypothyroidism affects the circadian rhythmicity of melatonin synthesis in a sex-dependent manner. [ABSTRACT FROM AUTHOR]

Southern stingrays (Hypanus americanus) are relatively large rays that are common and popular in public aquariums because of their size and gentle nature. In aquariums, as well as in the wild, female southern stingrays are fecund. They have a short gestation cycle and can sustain multiple pregnancies each year, each culminating with 2-10 young. This reproductive rate could quickly outpace capacity in managed care and result in a ray surplus. To prevent overpopulation, many aquaria have resorted to single sex groups with a preference for femaleonly populations. This is an effective way to control population growth, but forces the maintenance of two separated populations of rays; for females this interrupts normal reproductive cycling and replaces it with a protracted non-pregnant condition. An additional consideration is development of reproductive disease in females which is recognized by an enlarged, misshapen, and congested ovary with an abundance of cystic structures and an enlarged uterus with a thickened wall that is often filled with histotroph despite a non-pregnant status. There are no effective long-lasting medical treatments for this type of reproductive disease and mortality is often the result. This report describes a surgical technique for ovariectomy in southern stingrays including outcomes and complications. Ovariectomy as a surgical method prevents unwanted reproduction and has the benefit of reducing reproductive pathologies commonly observed in southern stingrays as they age. Seven stingrays 1-5.2years old and 42-83.5cm disc width underwent ovariectomy. After anesthesia, the ovary and a small amount of epigonal was excised via a left para-lumbar incision. Four of the seven rays survived five or more years postprocedure. Two rays died acutely of coelomitis and one ray died of complications unrelated to the procedure. This report details a surgical procedure for ovariectomy in southern stingrays including outcomes, complications, and recommendations. [ABSTRACT FROM AUTHOR]

During the development of animal organs, various adverse stimuli or toxic environments can induce oxidative stress and delay ovarian development. Paeoniflorin (PF), the main active ingredient of the traditional Chinese herb Paeonia lactiflora Pall., has protective effects on various diseases by preventing oxidative stress. However, the mechanism by which PF attenuates oxidative damage in mouse ovaries remains unclear. We evaluated the protective effects of PF on ovaries in an H2O2-induced mouse oxidative stress model. The H2O2-induced mouse ovarian oxidative stress model was used to explore the protective effect of PF on ovarian development. Histology and follicular development were observed. We then detected related indicators of cell apoptosis, oxidative stress, and autophagy in mouse ovaries. We found that PF inhibited H2O2-induced ovarian cell apoptosis and ferroptosis and promoted granulosa cell proliferation. PF prevented oxidative stress by increasing nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression levels. In addition, the autophagic flux of ovarian cells was activated and was accompanied by increased lysosomal biogenesis. Moreover, PF-mediated autophagy was involved in clearing mitochondria damaged by H2O2. Importantly, PF administration significantly increased the number of primordial follicles, primary follicles, secondary follicles, and antral follicles. PF administration improved ovarian sizes compared with the H2O2 group. The present study suggested that PF administration reversed H2O2-induced ovarian developmental delay and promoted follicle development. PF-activated mitophagy is crucial for preventing oxidative stress and improving mitochondrial quality. [ABSTRACT FROM AUTHOR]

Background: Energy allocation between growth and reproduction determines puberty onset and fertility. In mammals, peripheral hormones such as leptin, insulin and ghrelin signal metabolic information to the higher centres controlling gonadotrophin-releasing hormone neurone activity. However, these observations could not be confirmed in lower vertebrates, suggesting that other factors may mediate the energetic trade-off between growth and reproduction. A bioinformatic and experimental study suggested co-regulation of the circadian clock, reproductive axis and growth-regulating genes in zebrafish. While loss-of-function of most of the identified co-regulated genes had no effect or only had mild effects on reproduction, no such information existed about the co-regulated somatostatin, well-known for its actions on growth and metabolism. Results: We show that somatostatin signalling is pivotal in regulating fecundity and metabolism. Knock-out of zebrafish somatostatin 1.1 (sst1.1) and somatostatin 1.2 (sst1.2) caused a 20–30% increase in embryonic primordial germ cells, and sst1.2−/− adults laid 40% more eggs than their wild-type siblings. The sst1.1−/− and sst1.2−/− mutants had divergent metabolic phenotypes: the former had 25% more pancreatic α-cells, were hyperglycaemic and glucose intolerant, and had increased adipocyte mass; the latter had 25% more pancreatic β-cells, improved glucose clearance and reduced adipocyte mass. Conclusions: We conclude that somatostatin signalling regulates energy metabolism and fecundity through anti-proliferative and modulatory actions on primordial germ cells, pancreatic insulin and glucagon cells and the hypothalamus. The ancient origin of the somatostatin system suggests it could act as a switch linking metabolism and reproduction across vertebrates. The results raise the possibility of applications in human and animal fertility. [ABSTRACT FROM AUTHOR]

Introduction: Laying performance is a key factor affecting production efficiency in poultry, but its molecular mechanism is still indistinct. In this study, Yaoshan chickens, a local breed in Guizhou, China, and merchant chickens (GYR) with higher egg yield after the three-line cross improvement hybridization of Yaoshan chickens were used as animal samples. Methods: To explore the regulatory mechanism of the diversities in laying performance, RNA-seq and ultra-performance liquid chromatographytandem mass spectrometry (UPLC--MS/MS) were used to describe the transcriptional and metabolic profiles of the ovaries of Yaoshan and GYR chickens. Results: At the transcriptional level, 288 differentially expressed genes were upregulated in Yaoshan chickens and 353 differentially expressed genes were upregulated in GYR chickens. In addition, GSEA showed that ECM-receptor interactions and the TGF-β signaling pathway were restrained, resulting in increased egg production in GYR chickens. Furthermore, the upregulation of thiamine and carnitine was identified by metabolomic analysis to facilitate the laying performance of hens. Finally, comprehensive analyses of the transcriptome and metabolome found that thiamine and carnitine were negatively correlated with ECM-receptor interactions and the TGF-β signaling pathway, which jointly regulate the laying performance of Yaoshan chickens and GYR chickens. Discussion: Taken together, our research delineates differences in the transcriptional and metabolic profiles of the ovaries of Yaoshan and GYR chickens during the peak egg production period and provides new hypotheses and clues for further research on poultry egg production performance and the improvement of economic benefits. [ABSTRACT FROM AUTHOR]

Cell death is an important process in the body, as it occurs throughout every tissue during development, disease, and tissue regeneration. Phagocytes are responsible for clearing away dying cells and are typically characterized as either professional or nonprofessional phagocytes. Professional phagocytes, such as macrophages, are found in nearly every part of the body while nonprofessional phagocytes, such as epithelial cells, are found in every tissue type. However, there are organs that are considered “immune-privileged” as they have little to no immune surveillance and rely on nonprofessional phagocytes to engulf dying cells. These organs are surrounded by barriers to protect the tissue from viruses, bacteria, and perhaps even immune cells. The Drosophila ovary is considered immune-privileged, however the presence of hemocytes, the macrophages of Drosophila, around the ovary suggests they may have a potential function. Here we analyze hemocyte localization and potential functions in response to starvation-induced cell death in the ovary. Hemocytes were found to accumulate in the oviduct in the vicinity of mature eggs and follicle cell debris. Genetic ablation of hemocytes revealed that the presence of hemocytes affects oogenesis and that they phagocytose ovarian cell debris and in their absence fecundity decreases. Unpaired3, an IL-6 like cytokine, was found to be required for the recruitment of hemocytes to the oviduct to clear away obsolete follicle cells. These findings demonstrate a role for hemocytes in the ovary, providing a more thorough understanding of phagocyte communication and cell clearance in a previously thought immune-privileged organ. [ABSTRACT FROM AUTHOR]

Endometriosis (EM) is defined as the engraftment and proliferation of functional endometrial-like tissue outside the uterine cavity, leading to a chronic inflammatory condition. While the precise etiology of EM remains elusive, recent studies have highlighted the crucial involvement of a dysregulated immune system. The complement system is one of the predominantly altered immune pathways in EM. Owing to its involvement in the process of angiogenesis, here, we have examined the possible role of the first recognition molecule of the complement classical pathway, C1q. C1q plays seminal roles in several physiological and pathological processes independent of complement activation, including tumor growth, placentation, wound healing, and angiogenesis. Gene expression analysis using the publicly available data revealed that C1q is expressed at higher levels in EM lesions compared to their healthy counterparts. Immunohistochemical analysis confirmed the presence of C1q protein, being localized around the blood vessels in the EM lesions. CD68+ macrophages are the likely producer of C1q in the EM lesions since cultured EM cells did not produce C1q in vitro. To explore the underlying reasons for increased C1q expression in EM, we focused on its established pro-angiogenic role. Employing various angiogenesis assays on primary endothelial endometriotic cells, such as migration, proliferation, and tube formation assays, we observed a robust proangiogenic effect induced by C1q on endothelial cells in the context of EM. C1q promoted angiogenesis in endothelial cells isolated from EM lesions (as well as healthy ovary that is also rich in C1q). Interestingly, endothelial cells from EM lesions seem to overexpress the receptor for the globular heads of C1q (gC1qR), a putative C1q receptor. Experiments with siRNA to silence gC1qR resulted in diminished capacity of C1q to perform its angiogenic functions, suggesting that C1q is likely to engage gC1qR in the pathophysiology of EM. gC1qR can be a potential therapeutic target in EM patients that will disrupt C1q-mediated proangiogenic activities in EM. [ABSTRACT FROM AUTHOR]

Objectives: We present an Egyptian study on pediatric ovarian immature teratomas (ITs), aiming to clarify our treatment strategy selection. Methods: A retrospective review of all children with pure ovarian ITs who were treated at our institution between 2008 and 2023. The analysis included clinical characteristics, tumor staging according to Children's Oncology Group (COG), grading based on the Norris system, management, and outcomes. Results: Thirty-two patients were included, with a median age of 9 years. All patients underwent primary surgery. Unilateral salpingo-oophorectomy was performed in 31 patients. Surgical staging was completed in all patients. Based on COG staging, there were 28 patients (87.5%) stage I, 1 (3%) stage II, and 3 (9.5%) stage III. According to Norris classification, 16 patients (50%) were classified as grade I, 9 (28%) grade II, and 7 (22%) grade III. All patients in stage I were treated using surgery-alone approach, whereas the remaining four (12.5%) received adjuvant chemotherapy. Five patients in stage I had gliomatosis peritonei (GP), and none of them underwent extensive surgery. At a median follow-up of 86 months, two patients had events. The first patient (stage III/grade I) developed IT relapse on the operative bed, and the second (stage I/grade I) had a metachronous IT on the contralateral ovary. Both patients were successfully managed with surgery followed by second-line chemotherapy. Five-year overall survival and event-free survival for all patients were 100% and 93.4%, respectively. Conclusions: Surgery-alone strategy with close follow-up achieves excellent outcomes for localized ovarian ITs in children, irrespective of the Norris grading or the presence of GP. However, adjuvant chemotherapy is questionable for patients with incompletely resected or locally advanced tumors, and its role requires further evaluation through prospective multicentric studies with a larger sample size. [ABSTRACT FROM AUTHOR]

Background: The toxicity of silver nanoparticles (AgNPs) has been proven in the female reproductive system. Thymoquinone (TQ) is a natural antioxidant and bioactive component of Nigella sativa. Objective: We evaluated the efficacy of TQ on ovarian tissue following toxicity induced by AgNPs in female mice. Materials and Methods: 24 female NMRI mice (5-6 wk, an average weight of 33 gr) were randomly divided into 4 groups (n = 6/each): control, AgNPs (500 mg/kg, gavage), TQ (2.5 mg/kg, intraperitoneal injection), and TQ+AgNPs. Mice were treated every day for 35 days. Serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), luteinizing hormone, and follicle-stimulating hormone were measured. The optical disector and stereological techniques were utilized to estimate the follicular count, their volume at different developmental stages, and the structure of ovarian tissue. Results: In the AgNPs group, the serum concentrations of TAC (p = 0.01), luteinizing hormone (p < 0.001), follicle-stimulating hormone, the volume of corpus luteum (p < 0.001), and the number of follicles decreased significantly compared to the control group. Nevertheless, AgNPs significantly increased the MDA level. In the TQ+AgNPs group compared to the AgNPs group, a significant decrease in MDA level (p < 0.001) and a significant improvement in TAC (p = 0.03), and hormonal levels, the number of primary, preantral, and antral follicles (p = 0.04), and the volume of corpus luteum (p = 0.01) were observed. Conclusion: TQ improved the number of follicles by reducing oxidative stress and lipid peroxidation in AgNPs-damaged ovarian tissue. [ABSTRACT FROM AUTHOR]

Ex vivo follicle growth is an essential tool, enabling interrogation of folliculogenesis, ovulation, and luteinization. Though significant advancements have been made, existing follicle culture strategies can be technically challenging and laborious. In this study, we advanced the field through development of a custom agarose micromold, which enables scaffold-free follicle culture. We established an accessible and economical manufacturing method using 3D printing and silicone molding that generates biocompatible hydrogel molds without the risk of cytotoxicity from leachates. Each mold supports simultaneous culture of multiple multilayer secondary follicles in a single focal plane, allowing for constant timelapse monitoring and automated analysis. Mouse follicles cultured using this novel system exhibit significantly improved growth and ovulation outcomes with comparable survival, oocyte maturation, and hormone production profiles as established three-dimensional encapsulated in vitro follicle growth (eIVFG) systems. Additionally, follicles recapitulated aspects of in vivo ovulation physiology with respect to their architecture and spatial polarization, which has not been observed in eIVFG systems. This system offers simplicity, scalability, integration with morphokinetic analyses of follicle growth and ovulation, and compatibility with existing microphysiological platforms. This culture strategy has implications for fundamental follicle biology, fertility preservation strategies, reproductive toxicology, and contraceptive drug discovery. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to comprehensively analyze the clinical characteristics and treatment status of Chinese small cell carcinoma of the ovary hypercalcemic type (SCCOHT) patients, providing insights into this unique population and comparing findings with international literature. Methods: Through a meta-analysis, we collected data from published case reports and records from the Obstetrics & Gynecology Hospital of Fudan University. Demographic information, clinical presentations, tumor attributes, treatment modalities, and survival outcomes were extracted and examined alongside relevant global studies. Results: The analysis encompassed 80 Chinese SCCOHT patients, of which 62 from 33 previously reported literatures, and the other 18 were from Obstetrics & Gynecology Hospital of Fudan University. In 62 cases with stage information, A total of 25 tumors were International Federation of Gynecology and Obstetrics stage I, 3 were stage II, 19 were stage III, and 15 were stage IV. Most patients received surgery and chemotherapy, but regimens were varied. Median follow-up was 10 months (range=4-120). Elevated carbohydrate antigen 125 and serum calcium levels were consistent findings. Recurrence rates were notable, especially among stage I patients. Platinum-based chemotherapy, paclitaxel and carboplatin (n=11, 13.4%), constituted common treatment regimens. Conclusion: This study observed demographic and clinical similarities with international datasets. And the findings emphasize the urgency for innovative therapeutic approaches to improve outcomes in SCCOHT patients. Continued research efforts are essential to enhance the knowledge surrounding this rare malignancy and to optimize its clinical management. [ABSTRACT FROM AUTHOR]

Fasciolosis, a globally re-emerging zoonotic disease, is mostly caused by the parasitic infection with Fasciola hepatica, often known as the liver fluke. This disease has a considerable impact on livestock productivity. This study aimed to evaluate the fluke burdens and faecal egg counts in goats that were administered phage clones of cathepsin L mimotopes and then infected with F. hepatica metacercariae. Additionally, the impact of vaccination on the histology of the reproductive system, specifically related to egg generation in adult parasites, was examined. A total of twenty-four goats, which were raised in sheds, were divided into four groups consisting of six animals each. These groups were randomly assigned. The goats were then subjected to two rounds of vaccination. Each vaccination involved the administration of 1 × 1013 phage particles containing specific mimotopes for cathepsin L2 (group 1: PPIRNGK), cathepsin L1 (group 2: DPWWLKQ), and cathepsin L1 (group 3: SGTFLFS). The immunisations were carried out on weeks 0 and 4, and the Quil A adjuvant was used in combination with the mimotopes. The control group was administered phosphate-buffered saline (PBS) (group 4). At week 6, all groups were orally infected with 200 metacercariae of F. hepatica. At week 22 following the initial immunisation, the subjects were euthanised, and adult F. hepatica specimens were retrieved from the bile ducts and liver tissue, and subsequently quantified. The specimens underwent whole-mount histology for the examination of the reproductive system, including the testis, ovary, vitellaria, Mehlis' gland, and uterus. The mean fluke burdens following the challenge were seen to decrease by 50.4%, 62.2%, and 75.3% (p < 0.05) in goats that received vaccinations containing cathepsin L2 PPIRNGK, cathepsin L1 DPWWLKQ, and cathepsin L1 SGTFLFS, respectively. Animals that received vaccination exhibited a significant reduction in the production of parasite eggs. The levels of IgG1 and IgG2 isotypes in vaccinated goats were significantly higher than in the control group, indicating that protection is associated with the induction of a mixed Th1/Th2 immune response. The administration of cathepsin L to goats exhibits a modest level of efficacy in inducing histological impairment in the reproductive organs of liver flukes, resulting in a reduction in egg output. [ABSTRACT FROM AUTHOR]

The obesity epidemic continues to increase, with half of US women predicted to be obese by 2030. Women with obesity are at increased risk for not only cardiovascular and liver disease, but also reproductive disorders. Although mouse models are useful in studying the effects of obesity, there is inconsistency in obesity-induction methods, diet composition, and mouse strains, and studies using female mice are limited. In this study, we sought to compare the effects of a 45% high-fat diet (HFD) versus a 60% HFD on the uterine estrous cycle of nulligravid C57BL/6J mice. For 22 weeks, we placed a total of 20 mice on either a 60% HFD, 45% HFD, or each HFD-matched control diet (CD). Both HFDs produced significant weight gain, with 60% HFD and 45% HFD gaining significant weight after 2 weeks and 15 weeks, respectively. Additionally, both HFDs led to glucose intolerance, fatty liver, and adipocyte hypertrophy. Mice fed 60% HFD displayed hyperphagia in the first 12 weeks of HFD treatment. Moreover, 60% HFD-treated mice had a longer estrous cycle length and an increased percentage of estrus stage samplings compared to CD-treated mice. Estrous cycle stage-controlled 60% HFD-treated mice displayed an increased estrogen-to-progesterone ratio and decreased ovarian corpora lutea compared to CD-treated mice, which may underlie the observed estrous cycle differences. There was no significant difference between diets regarding endometrial morphology or the percent of endometrial CD45+ immune cells. Our results indicate that consideration is needed when selecting a HFD-induced obesity mouse model for research involving female reproductive health. [ABSTRACT FROM AUTHOR]

Per- and poly-fluoroalkylated substances (PFAS) are a large group of chemicals that persist both in the environment and in the body. Legacy PFAS, e.g., perfluorooctanoic acid and perfluorooctane sulfonic acid, are implicated as endocrine disruptors and reproductive and developmental toxicants in epidemiological and animal model studies. This review describes female reproductive outcomes of reported studies and includes where associative relationships between PFAS exposures and female reproductive outcomes have been observed as well as where those are absent. In animal models, studies in which PFAS are documented to cause toxicity and where effects are lacking are described. Discrepancies exist in both human and animal studies and are likely attributable to human geographical contamination, developmental status, duration of exposure, and PFAS chemical identity. Similarly, in animal investigations, the model used, exposure paradigm, and developmental status of the female are important and vary widely in documented studies. Taken together, support for PFAS as reproductive and developmental toxicants exists, although the disparity in study conditions and human exposures contribute to the variation in effects noted. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by abnormal steroid hormone levels in peripheral blood and poor-quality oocytes. In the ovary, androgen is produced by theca cells, and estrogen is produced by granulosa cells. Androgen is converted to estrogen in granulosa cells, with cytochrome P450 aromatase as the limiting enzyme during this process. Estrogen receptors (ER) include ER alpha, ER beta, and membrane receptor GPR30. Studies have demonstrated that the abnormal functions of estrogen and its receptors and estradiol synthesis-related enzymes are closely related to PCOS. In recent years, some estrogen-related drugs have made significant progress in clinical application for subfertility with PCOS, such as letrozole and clomiphene. This article will elaborate on the recent advances in PCOS caused by abnormal expression of estrogen and its receptors and the application of related targeted small molecule drugs in clinical research and treatment. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) stem cell models of the ovary have the potential to benefit womens reproductive health research. One such model, the reconstituted ovary (rOvary) self-assembles with pluripotent stem cell-derived germ cells creating a 3D ovarian mimic competent to support the differentiation of functional oocytes inside follicles. In this study, we evaluated the cellular composition of the rOvary revealing the capacity to generate multiple follicles surrounded by NR2F2+ stroma cells. However, the rOvary does not develop a surface epithelium, the source of second-wave pre-granulosa cells, or steroidogenic theca. Therefore, the rOvary models represent the self-assembly of activated follicles in a pre-pubertal ovary poised but not yet competent for hormone production.

Cells migrate collectively through confined environments during development and cancer metastasis. The nucleus, a stiff organelle, impedes single cells from squeezing into narrow channels within artificial environments. However, how nuclei affect collective migration into compact tissues is unknown. Here, we use border cells in the fly ovary to study nuclear dynamics in collective, confined in vivo migration. Border cells delaminate from the follicular epithelium and squeeze into tiny spaces between cells called nurse cells. The lead cell nucleus transiently deforms within the lead cell protrusion, which then widens. The nuclei of follower cells deform less. Depletion of the Drosophila B-type lamin, Lam, compromises nuclear integrity, hinders expansion of leading protrusions, and impedes border cell movement. In wildtype, cortical myosin II accumulates behind the nucleus and pushes it into the protrusion, whereas in Lam-depleted cells, myosin accumulates but does not move the nucleus. These data suggest that the nucleus stabilizes lead cell protrusions, helping to wedge open spaces between nurse cells.

The purpose of this research was to determine the correlation between the weight of the ovary, the number of follicles, and the quality of the oocytes from the culling female bovine obtained from the slaughterhouse. The variation may affect the potential of the ovary to produce follicles. Paired ovaries were obtained from female bovines. Follicle numbers were recorded and divided into three size categories (small: 3 mm, medium: < 3 mm-8 mm, and large: > 8 mm). Oocytes were aspirated and the number of oocytes was recorded and graded into four categories (grades A, B, C, and D). There was a positive correlation between the weight of the ovary and the number of follicles, which is 0.560 with the regression equation y = 3.52 + 0.501 x. There was a positive correlation between the number of follicles and the number of oocytes, which is 0.546 with the regression equation y =2.48 + 1.204 x. There was a positive correlation between the number of oocytes and the grade of oocytes, which is 0.520, with the regression equation y = 0.93 + 0.800 x. There was no correlation between the weight of the ovary and oocyte grade A, which is 0.013.

Objective: Mitotically active cellular fibroma (MACF) of the ovary, characterized by relatively high mitotic activity without severe atypia, was first described in the WHO classification in 2014. However, due to its rarity, the clinicopathological characteristics of ovarian MACF have not been established. This study was performed to describe the clinical, radiological, and pathological features of MACF by analyzing 11 cases of ovarian MACF. Materials and methods: Between 2015 and 2022, 11 patients with ovarian MACFs underwent surgical treatment at our institution. Clinicopathologic data of the patients were retrospectively reviewed from their medical records. Results: Median patient age was 53.7 years (range 21–77 years), and median tumor diameter was 7.8 cm (range 4.3–14.0 cm). Preoperative CA125 was elevated in 4 cases. Four of the eleven patients had abdominal pain, and two presented with vulvar pain or a palpable abdominal mass, respectively. Preoperative radiological impressions included fibroma, fibrothecoma, stromal tumor, and cystadenocarcinoma. A laparoscopic approach was adopted in 7 cases (64%). Intraoperative frozen section was performed in 5 patients, and all demonstrated the presence of a benign, fibromatous stromal tumor. Three patients underwent fertility-sparing surgery, including laparoscopic ovarian cystectomy and unilateral salpingo-oophorectomy. Median follow-up was 37.7 months (range 2–84 months), and no patient experienced disease relapse or died of their disease. Conclusion: This study shows that ovarian MACF has a benign clinical course. Fertility-sparing surgery provides a safe therapeutic option for MACF, which can be managed safely by laparoscopy. Imaging findings and final pathological diagnosis were not well matched. Intraoperative frozen section is important for determining surgical extent in mitotically active cellular fibroma of the ovary.

Ovarian lymphangiomas are rare benign neoplasms characterized by the proliferation of lymphatic vessels within the ovarian tissue. While lymphangiomas can manifest in various anatomical locations, their occurrence within the ovaries is exceptionally uncommon, posing diagnostic and therapeutic challenges for clinicians. The aetiology of ovarian lymphangiomas remains elusive, with theories suggesting congenital malformations, lymphatic obstruction, or acquired lymphatic proliferation as potential contributing factors. The clinical presentation of ovarian lymphangiomas often includes nonspecific symptoms such as abdominal pain, swelling, or discomfort, leading to difficulties in early detection and diagnosis. Radiological imaging, particularly Ultrasound, CT (computed tomography) and MRI (magnetic resonance imaging), plays a crucial role in identifying these lesions and guiding subsequent management strategies. Despite their generally benign nature, ovarian lymphangiomas can attain significant sizes, causing complications such as torsion, rupture, or compression of adjacent structures. Surgical intervention, typically in cystectomy or oophorectomy, is frequently pursued to alleviate symptoms and prevent potential complications. This paper aims to comprehensively review the existing literature on ovarian lymphangiomas, addressing their clinical presentation, diagnostic challenges, and management strategies. By synthesizing available data, we seek to enhance our understanding of this rare entity, providing valuable insights for clinicians encountering similar cases. Improved awareness and knowledge of ovarian lymphangiomas are essential for timely diagnosis and optimal patient outcomes.

Abstract Background Stathmin, a cytosolic microtubule-destabilizing phosphoprotein involved in the regulation of mitosis, is widely expressed in various malignancies and acts as an adverse prognostic factor. Our research analyzed its immunohistochemical expression on a large cohort of ovarian sex cord-stromal tumors, evaluating its potential utility in differential diagnosis, prognosis, and therapeutic application. Methods We examined 390 cases of ovarian sex cord-stromal tumors including 281 adult granulosa cell tumors (AGCT), 5 juvenile granulosa cell tumors (JGCT), 33 Sertoli-Leydig cell tumors (SLCT), 50 fibromas/thecomas (F/T), 11 Leydig cell tumors/steroid cell tumors (LCT/SterCT), 5 sex-cord stromal tumors NOS (SCST-NOS), 3 Sertoli cell tumors (SCT), and 2 sclerosing stromal tumors (ScST). Immunohistochemical analysis was performed using TMAs. Results Strong expression (> 50%) was observed in all cases of AGCT, JGCT, SLCT, SCST-NOS, SCT and 1 ScST. The other case of ScST exhibited mild expression (5–10%). The negative cases included exclusively F/T and LCT/SterCT, with F/T showing 24% of negative cases and LCT/SterCT comprising 64% of negative cases. Conclusion The results of our study indicate that stathmin is neither a prognostic marker nor suitable for the differential diagnosis of challenging cases of ovarian sex cord-stromal tumors. However, its predictive value may be theoretically significant, as a decrease in stathmin expression potentialy influences response to chemotherapy treatment.

Abstract The idea of utilizing unused oocytes present in the ovaries has been tested in various ways to produce offspring. However, only a limited number of studies succeeded in offspring generation. They include transplantation of ovaries into autologous or allogeneic animals, and acquisition of pups from oocytes obtained by transplanting mouse ovaries into immunodeficient rats. Here we report successful production of rat oocytes by transplanting rat ovaries under the kidney capsule of immunodeficient mice with addition of hormone administration to the mice. In addition, these oocytes were developed by in vitro fertilization, and transplanted into the oviducts of pseudopregnant rats, resulting in successful delivery of pups. The modified gene of the donor rat was confirmed to be correctly inherited to the pups. These results show that xenotransplantation of ovarian tissue makes it possible to leave offspring, beginning a new phase in developmental engineering.

Background: Infertility is a health problem that affects approximately 10-15% of couples trying to achieve pregnancy worldwide. Various studies have shown that Nigella sativa (N. Sativa) has many health benefits, including reproductive health. However, studies examining the effectiveness of N. Sativa in preventing folliculogenesis disorders have never been reported. Purpose: This study aims to determine the benefits of administering N. Sativa in preventing folliculogenesis disorders as measured by the diameter of the antral follicles and the thickness of the granulosa cell layer. Methods: This research design uses an experiment with a randomized posttest-only controlled group design approach. There were 27 experimental animals (mice) divided into three groups, namely the negative control group (9 animals) and the positive control group (9 animals), as well as the treatment group (9 animals). The positive control group was exposed to two cigarettes of cigarette smoke per day. The treatment group was exposed to cigarette smoke and N. Sativa 300 mg/KgBW/day for 28 days. After that, the mice were sacrificed to take their ovaries. Then, the ovarian organ samples were stained with Hematoxylin-eosin and examined for the diameter of the antral follicles and the thickness of the granulosa cell layer in the antral follicles with photo slides at 400x magnification in 5 fields of view, statistical analysis using the Independent T-test. Results: There were significant differences in antral follicle diameter and granulosa cell thickness in mice exposed to cigarette smoke and N. Sativa. Administration of N. Sativa extract can increase granulosa cell thickness through estrogenic function. Administration of N. Sativa extract showed estrogenic activity by increasing serum estradiol levels. N. Sativa heterotrophic activity cannot be separated from the flavonoid and phenolic compounds contained in N. Sativa, which have been proven to have high estrogenic activity. Conclusion: N. Sativa extract is efficacious in improving the diameter of antral follicles and the thickness of granulosa cells caused by exposure to cigarettes.

Abstract A 27-year-old man was admitted to the hospital after a year of marriage due to infertility. During laparoscopic exploratory surgery, the presence of a retrovesical uterus was clearly observed, and the gonadal organs were visible on both sides. However, the testicles or ovaries were not identifiable, nor were the spermatic vessels and fallopian tubes at the joint. Intraoperative bilateral gonad biopsy was performed. Cryopreservation of the right gonadal gland revealed gonadoblastoma and malignant germinoma (asexual tumor/seminoma) with sclerosis and atrophy of testicular tissue. No proliferation of germ cells and sertoli cells was observed in spermatic tubule. The left gonad was diagnosed as a gonadoblastoma. Finally, total hysterectomy and bilateral gonadal tumor organectomy were performed to seal the vaginal stump. Local radiotherapy was administered after surgery. In general, tumors were found on both sides of the gonads, especially gonadoblastoma and malignant germinoma on the right side and gonadoblastoma on the left side.

Abstract Background Secreted frizzled-related proteins (SFRPs) comprise a family of WNT signaling antagonists whose roles in the ovary are poorly understood. Sfrp4-null mice were previously found to be hyperfertile due to an enhanced granulosa cell response to gonadotropins, leading to decreased antral follicle atresia and enhanced ovulation rates. The present study aimed to elucidate the mechanisms whereby SFRP4 antagonizes FSH action. Methods Primary cultures of granulosa cells from wild-type mice were treated with FSH and/or SFRP4, and effects of treatment on gene expression were evaluated by RT-qPCR and RNAseq. Bioinformatic analyses were conducted to analyse the effects of SFRP4 on the transcriptome, and compare them to those of FSH or a constitutively active mutant of FOXO1. Additional granulosa cell cultures from wild-type or Sfrp4-null mice, some pretreated with pharmacologic inhibitors of specific signaling effectors, were used to examine the effects of FSH and/or SFRP4 on signaling pathways, autophagy and apoptosis by western blotting and TUNEL. Results Treatment of cultured granulosa cells with recombinant SFRP4 was found to decrease basal and FSH-stimulated mRNA levels of FSH target genes. Unexpectedly, this effect was found to occur neither via a canonical (CTNNB1-dependent) nor non-canonical WNT signaling mechanism, but was found to be GSK3β-dependent. Rather, SFRP4 was found to antognize AKT activity via a mechanism involving AMPK. This lead to the hypophosphorylation of FOXO1 and a decrease in the expression of a portion of the FSH and FOXO1 transcriptomes. Conversely, FSH-stimulated AMPK, AKT and FOXO1 phosphorylation levels were found to be increased in the granulosa cells of Sfrp4-null mice relative to wild-type controls. SFRP4 treatement of granulosa cells also induced autophagy by signaling via AKT-mTORC1-ULK1, as well as apoptosis. Conclusions This study identifies a novel GSK3β-AMPK-AKT signaling mechanism through which SFPR4 antagonizes FSH action, and further identifies SFRP4 as a novel regulator of granulosa cell autophagy. These findings provide a mechanistic basis for the phenotypic changes previously observed in Sfrp4-null mice, and broaden our understanding of the physiological roles of WNT signaling processes in the ovary.

Abstract Objectives We present an Egyptian study on pediatric ovarian immature teratomas (ITs), aiming to clarify our treatment strategy selection. Methods A retrospective review of all children with pure ovarian ITs who were treated at our institution between 2008 and 2023. The analysis included clinical characteristics, tumor staging according to Children’s Oncology Group (COG), grading based on the Norris system, management, and outcomes. Results Thirty-two patients were included, with a median age of 9 years. All patients underwent primary surgery. Unilateral salpingo-oophorectomy was performed in 31 patients. Surgical staging was completed in all patients. Based on COG staging, there were 28 patients (87.5%) stage I, 1 (3%) stage II, and 3 (9.5%) stage III. According to Norris classification, 16 patients (50%) were classified as grade I, 9 (28%) grade II, and 7 (22%) grade III. All patients in stage I were treated using surgery-alone approach, whereas the remaining four (12.5%) received adjuvant chemotherapy. Five patients in stage I had gliomatosis peritonei (GP), and none of them underwent extensive surgery. At a median follow-up of 86 months, two patients had events. The first patient (stage III/grade I) developed IT relapse on the operative bed, and the second (stage I/grade I) had a metachronous IT on the contralateral ovary. Both patients were successfully managed with surgery followed by second-line chemotherapy. Five-year overall survival and event-free survival for all patients were 100% and 93.4%, respectively. Conclusions Surgery-alone strategy with close follow-up achieves excellent outcomes for localized ovarian ITs in children, irrespective of the Norris grading or the presence of GP. However, adjuvant chemotherapy is questionable for patients with incompletely resected or locally advanced tumors, and its role requires further evaluation through prospective multicentric studies with a larger sample size.

Ovarian carcinoid is a rare well-differentiated neuroendocrine tumor resembling those arising in the gastrointestinal tract. We present a case of ovarian carcinoid with magnetic resonance imaging (MRI) findings. A 50-year-old woman with genital bleeding and severe constipation was referred to our hospital. On MR imaging, a left ovarian tumor showed iso to high signal intensity on T1-weighted images (T1WI), relatively low signal intensity on T2WI, and slightly high signal intensity on diffusion-weighted images. Additionally, the tumor demonstrated early and delayed strong contrast enhancement on dynamic contrast-enhanced images. The tumor was pathologically diagnosed with ovarian strumal carcinoid. High signal intensity on T1WI should be recognized as the MRI findings in ovarian carcinoids.

Juvenile granulosa cell tumour (JGCT) is very uncommon gynecological malignancy that occurs more commonly in under five years old of age. We describe a case of JGCT in a 4-years old girl. The malignancy is assigned to International Federation of Gynecology and Obstetric staging system (FIGO stage I). Treated with complete excision only, the patient showed no evidence of relapse one year after surgery. Findings in this case are discussed and histological examination confirmed the diagnosis. The naturalhistory of JGCT, epidemiology, histology, treatment and prognosis are reviewed along with the case presentation.

The present study aimed to identify the novel mechanisms regulating rabbit fecundity. For this purpose, the association between litter size variability, fecundity, ovarian morphology, and markers of proliferation, apoptosis, steroidogenesis, and the presence of regulatory proteins were examined in ovarian cells from two rabbit lines divergently selected for low (LL) and high (HL) variability in litter size throughout sixteen generations. Ovaries and uteri were isolated from multiparous non-lactating female rabbits from each line at sixteen generations of selection. One part of the ovary was subjected to histomorphometric analysis of folliculogenesis. From the rest of ovary, ovarian granulosa cells (OGCs) were isolated, cultured, and cell viability, proliferation (accumulation of PCNA and of cyclin B1, and BrdU-positive cells), and apoptosis (accumulation of caspase 3, bax and DNA fragmentation) were evaluated by the Trypan blue exclusion test and BrdU, quantitative immunocytochemistry, and cell death detection assays. Furthermore, OGCs were subjected to proteomic analysis by using the nano HPLC-Chip-MS/MS method. The release of progesterone and oestradiol was measured by ELISA. The LL had more than one kit per litter than the HL (7.6 kits vs. 6.5 kits, p ≤ 0.05). No differences were found in the diameter of primordial and primary ovarian follicles, theca, and granulosa thickness, but the diameter of oocytes in the primary and secondary follicles was higher in the LL than in the HL (88.49 µm in the LL vs. 77.86 µm in the HL for oocytes of primary follicles, p ≤ 0.05; 122.10 µm in the LL vs. 109.87 µm in the HL for oocytes of secondary follicles, p ≤ 0.05). Preovulatory follicles were presented only in the ovaries of the LL. The LL had higher incorporation of BrdU and reduced accumulation of bax within OGCs (0.92% in the LL vs. 0.44% in the HL for incorporation of BrdU, p ≤ 0.05; 41% in the LL vs. 48% in the HL for accumulation of bax, p ≤ 0.05). Ovarian fragments from the LL produced less progesterone and oestradiol than those of the HL (12 ng/mg tissue/day in the LL vs, 45 ng/mg tissue/day in the HL for progesterone, p ≤ 0.05; 11 ng/mg tissue/day in the LL vs. 30 ng/mg tissue/day in the HL for oestradiol, p ≤ 0.05). Besides, the OGCs from the LL produced a higher number of specific regulatory proteins involved in cell differentiation, proliferation, and adhesion than the HL (50 vs 38, p ≤ 0.05). In conclusion, higher prolificacy in the LL line would be caused by: (1) the selection of growing primordial ovarian follicles; (2) better transformation to preovulatory follicles; (3) increased cytoplasmic maturation of oocytes; (4) increased DNA synthesis and decreased cytoplasmic apoptosis in OGCs; (5) changes in ovarian steroidogenesis; and (6) changes in the number of peptides involved in cell differentiation, proliferation, and adhesion.HIGHLIGHTS Assessing fecundity in two divergently rabbit lines for variability in litter size. Fecundity and its variability are related to the diameter and quality of oocytes. Selection and better growth of preovulatory follicles have been related to fecundity.

AbstractChinese herbs contain substances that regulate female hormones. Our study confirmed that Zingiberis rhizoma carbonisata contains Zingiberis rhizoma-based carbon dots (ZR-CDs), which exert regulatory effects on serum oestradiol and FSH in mice and show impacts on endometrial growth and follicular development that potentially affect the ability of female fertility. ZR-CDs were characterized to clarify the microstructure, optical features, and functional group characteristics. It shows that ZR-CDs are spherical carbon nanostructures ranging from 0.97 to 2.3 nm in diameter, with fluorescent properties and a surface rich in functional groups. We further investigated the impact of ZR-CDs on oestradiol and FSH in serum, growth, and the development of ovarian and uterine using normal female mice and exogenous oestradiol intervention model. It was observed that ZR-CDs accelerated oestrogen metabolism and attenuated oestradiol-induced endometrial hyperplasia. Simultaneously, ZR-CDs triggered an increase in FSH, even in the presence of high-serum oestradiol that inhibits FSH secretion. Our findings suggest that ZR-CDs could be a potential therapeutic treatment for anovulatory menstruation.

The Pacific white shrimp Penaeus vannamei is one of the most productive shrimp species in China and the world. Domestic demand for P. vannamei has increased annually because of its fast growth, easy breeding, strong resistance to stress and disease, and high meat yield. The primary challenge in the development of the shrimp industry is seed rearing. The demand for broodstocks of P. vannamei in China is as high as 1, 000, 000 pairs per year, and the total weight of shrimp seedlings exceeds 1.3 trillion. China needs to import 300, 000 pairs of P. vannamei every year. The cost of each pair of P. vannamei is approximately 200 US＄, thus equating to hundreds of millions of US＄ in total. During the production of P. vannamei, the spawning frequency varies greatly among female shrimp. Cultivating high-fecundity P. vannamei through genetic improvement is an effective way to reduce the cost of seedling farms and improve economic benefits.To further study the molecular mechanisms of fecundity differences in female P. vannamei, the ovarian histology and expression of four candidate genes in populations with high- and low-fecundity were analyzed in this study. Before the experiment, the 7-month-old parent shrimp of P. vannamei were fed a commercial parent shrimp fortified diet, a maturation promoting diet, and squid for nutritional enhancement. After one month of promoting maturity, the unilateral eyestalk of female shrimp was cut using forceps, and next-generation family construction began after 15–20 days of recovery. The spawning frequency of 439 female shrimp in the 30-day production cycle was calculated and used to indicate fecundity. Those with a spawning frequency of 0 were included in the low-fecundity group, while those with a spawning frequency of > 3 were included in the high-fecundity group. The ovarian development of P. vannamei was divided into four stages (proliferation, small growth, large growth, and maturation) according to the color, size, and shape of the ovaries. In the high-fecundity group, the ovaries exhibited development up to stageⅣ, indicating their attainment of maturity. In the low-fecundity group, ovarian development was limited to stageⅢ, with progression to stageⅣ proving difficult. Ovarian tissues from the same part of female shrimp of stageⅠ–Ⅳ in the high-fecundity group and stageⅠ–Ⅲ in the low-fecundity group were taken and immediately immersed in tissue fixative for paraffin sectioning. The research team previously identified candidate genes related to fecundity in genomic regions undergoing selective sweep in isolated populations. These included thioredoxin 2 (TRX2), partitioning-defective 3 (PARD3), phospholipase Cβ4 (PLCβ4), and arginine-glutamate acid dipeptide repeats (RERE), which play important roles in oocyte maturation, cell proliferation, and early development in other species. qRT-PCR was used to analyze and compare their expression in the ovary and eyestalk tissues of high- and low-fecundity females at different stages of ovarian development.The results of paraffin section showed that the ovarian development of the low-fecundity group was slower than that of the high-fecundity group. In the high-fecundity group, stageⅠ ovaries primarily consisted of oogonia and oocytes during the early phase of yolk formation, with the emergence of small spherical yolk granules. StageⅠ ovaries in the low-fecundity group primarily consisted of oogonia, with no observable yolk granule formation. StageⅡ ovaries in the high-fecundity group were mainly composed of oocytes with vitelline formation, accompanied by a notable augmentation in both the size and number of yolk granules. StageⅡ ovaries in the low-fecundity group primarily comprised oocytes in the early phase of vitelline formation with yolk granules beginning to form. StageⅢ ovaries in the high-fecundity group consisted mainly of oocytes during the late phase of yolk formation. Many spherical yolk granules were formed in the cytoplasm, and cortical rods began to appear, although the lengths of the cortical rods were short. StageⅢ ovaries in the low-fecundity group were composed of oocytes during yolk formation. The cytoplasm was full of spherical yolk granules in the absence of cortical rods. In the high-fecundity group, stage Ⅳ ovaries were filled with mature oocytes, large yolk granules filled the entire cytoplasm, and thick cortical rods were formed in the oocytes. qRT-PCR showed that the four genes maintained high expression levels in the mature ovaries of the high-fecundity group. Their expression levels in the ovaries of the high-fecundity group were higher than those in the ovaries of the low-fecundity group in the small and large growth stages. TRX2, PLCβ4, and RERE expression levels were significantly different between the groups (P < 0.05). In eyestalk tissues at different stages, TRX2, PARD3, PLCβ4, and RERE expression levels in the low-fecundity group were higher than those in the high-fecundity group. The results suggest that these four genes may play important roles in the ovarian development of P. vannamei. The expression levels of all four genes in the high-fecundity group were lower than those in the low-fecundity group in eyestalk tissues. However, in ovarian tissues, except for the PARD3 gene in stageⅠ, which was expressed at lower levels in the high-fecundity group than in the low-fecundity group, the expression levels of all four genes in the other stages were higher in the high-fecundity group than those in the low-fecundity group, which is opposite to the expression trend in eyestalk tissues. Therefore, we speculate that these genes also promote cell proliferation, development, and target gene expression in the eyestalks of the low-fecundity group. Their high expression in the eyestalks of the low-fecundity group may enhance the secretion of ovarian inhibitory factors, thereby inhibiting ovarian development. Further research is needed to reveal their functional mechanisms. The above results provide an important reference for the in-depth study of the molecular mechanisms of differences in the fecundity of female P. vannamei.

Background and purpose: Paraquat is one of the chemical herbicides with high toxicity. In case of incorrect consumption, this chemical causes fatal poisoning in people, especially those active in the field of agriculture. Nowadays, using compounds of natural origin to improve or reduce the harmful effects of agricultural pesticides is one of the important issues that has attracted the attention of researchers in this field. Quercetin as a natural flavonoid is found in large quantities in fruits and vegetables. As a kind of natural antioxidant, this compound has great power in removing free radicals. The purpose of this research was to evaluate the protective effects of quercetin on ovarian toxicity caused by paraquat in rats. Materials and methods: To conduct this experimental research, 30 adult Wistar rats with an average age of 6 to 8 months and a weight range of 160 to 180 gr were randomly divided into 5 experimental groups including 6 rats in each group. Paraquat (1.25 mg/kg, intraperitoneally) was injected into mice. Then quercetin was injected intraperitoneally in concentrations of 50, 100, and 200 mg/kg. The negative control group received only normal saline. After 24 hours, the animals were sacrificed and their ovaries were evaluated for changes in oxidative stress indices. Results: The results showed that paraquat significantly increased the reactive oxygen species (ROS), protein carbonyl, and lipid peroxidation, and significantly decreased glutathione content and survival of ovarian tissue cells when compared with the control group (P

Clock genes play a pivotal role in the rhythm maturation of bony fish ovaries. To explore the role of clock genes in the rhythmic ovarian development and maturation of tongue sole (Cynoglossus semilaevis), we used real-time fluorescent quantitative PCR technique to analyze the expression profiles of circadian locomotor output cycles Kaput 1a (Clock1a), brain and muscle Arntlike 1a (Bmal1a), Cryptochrome 1a (Cry1a), Cryptochrome 2 (Cry2), and Period 2 (Per2) at the ovarian stages Ⅱ, Ⅲ, Ⅳ, Ⅴ, and Ⅵ.The coding DNA sequence (CDS) of five clock genes were cloned and phylogenetically analyzed. We found that the CDS sequence length of Clock1a was 1 620 bp and encoded 539 amino acids, with the encoded amino acid sequence of Clock1a having a predicted molecular weight of 81.9 kDa. Clock1a has the functional domain PASD1 (consisting of 64 amino acids) and PAS11 (consisting of 103 amino acids). The CDS sequence length of Bmal1a was 1 881 bp and encoded 626 amino acids, with the encoded amino acid sequence of Bmal1a having a predicted molecular weight of 68.9 kDa. In the Bmal1a sequence, the functional domain PASD3 is composed of 63 amino acids, and the functional domain PAS11 is composed of 103 amino acids. The CDS sequence length of Cry1a was 1 896 bp and encoded 631 amino acids, with the encoded amino acid sequence of Cry1a having a predicted molecular weight of 71.4 kDa. Its functional domain FAD7 was composed of 199 amino acids. The CDS sequence length of Cry2 was 2 007 bp and encoded 669 amino acids, with the encoded amino acid sequence of Cry2 having a predicted molecular weight of 76.0 kDa. The Cry2 sequence contains a functional domain FAD7 consisting of 199 amino acids. The CDS sequence length of Per2 was 4 248 bp, encoding 1 415 amino acids, and the encoded amino acid sequence of Per2 has a predicted molecular weight of 154.0 kDa. In the Per2 sequence, the functional domain PeriodC consists of 295 amino acids and a functional domain PAS11 consists of 102 amino acids.The neighbor-joining method was used to analyze the Clock1a, Bmal1a, Cry1a, Cry2, and Per2 phylogenetic relationships between C. semilaevis and other bony fish, amphibians, birds, and mammals. The homology of Clock1a, Bmal1a, Cry1a, Cry2, and Per2 with other bony fish was 60%–79%, 94%–100%, 85%–91%, 84%–94%, and 70%–84%, respectively. Therefore, we believe that these five amino acid sequences show strong conserved property. In addition, the homology of Cry1a and Cry2 was 62%, indicating that Cry1a and Cry2 evolved differently during the evolution of C. semilaevis. In the constructed phylogenetic tree, Clock1a, Bmal1a, Cry1a, Cry2, and Per2 of C. semilaevis were clustered together with other bony fishes, indicating a close relationship between C. semilaevis and other bony fish in the evolutionary process. Moreover, the homology of Clock1a between C. semilaevis and mammals, birds, and amphibians is low, indicating that there are evolutionary differences in the evolutionary process of Clock1a. The high homology of Bmal1a, Cry1a, Cry2, and Per2 with mammals, birds, and amphibians suggests that these four clock genes were strongly conserved during the evolution of C. semilaevis.In the present study, we found that the expression levels of five clock genes were high in stagesⅡ and Ⅲ, which were equivalent to the non-reproductive season (P < 0.05). However, the expression levels of five clock genes were low in stages Ⅳ and Ⅴ, which were equivalent to the reproductive season (P < 0.05). Therefore, the expression profiles of Clock1a, Bmal1a, Cry1a, Cry2, and Per2 in the ovaries of C. semilaevis also have seasonal characteristics. The ovarian development and maturation of C. semilaevis goes through stages Ⅱ, Ⅲ, Ⅳ, Ⅴ, and Ⅵ, and then reaches stage Ⅱ again and starts a new reproductive cycle. The variation patterns of seasonal factors, such as light and temperature, in fish ovaries were consistent with the annual expression patterns of the five clock genes in this study. Therefore, it can be considered that the expression of clock genes in C. semilaevis has an annual cycle. The findings presented in this study can enrich the theory of ovarian development and maturation of C. semilaevis and provide a theoretical basis for improving breeding technology and seedling efficiency.

Abstract Background The common marmoset, Callithrix jacchus, is an invaluable model in biomedical research. Its use includes genetic engineering applications, which require manipulations of oocytes and production of embryos in vitro. To maximize the recovery of oocytes suitable for embryo production and to fulfil the requirements of the 3R principles to the highest degree possible, optimization of ovarian stimulation protocols is crucial. Here, we compared the efficacy of two hormonal ovarian stimulation approaches: 1) stimulation of follicular growth with hFSH followed by triggering of oocyte maturation with hCG (FSH + hCG) and 2) stimulation with hFSH only (FSH-priming). Methods In total, 14 female marmosets were used as oocyte donors in this study. Each animal underwent up to four surgical interventions, with the first three performed as ovum pick-up (OPU) procedures and the last one being an ovariohysterectomy (OvH). In total, 20 experiments were carried out with FSH + hCG stimulation and 18 with FSH-priming. Efficacy of each stimulation protocol was assessed through in vitro maturation (IVM), in vitro fertilization (IVF) and embryo production rates. Results Each study group consisted of two subgroups: the in vivo matured oocytes and the oocytes that underwent IVM. Surprisingly, in the absence of hCG triggering some of the oocytes recovered were at the MII stage, moreover, their number was not significantly lower compared to FSH + hCG stimulation (2.8 vs. 3.9, respectively (ns)). While the IVM and IVF rates did not differ between the two stimulation groups, the IVF rates of in vivo matured oocytes were significantly lower compared to in vitro matured ones in both FSH-priming and FSH + hCG groups. In total, 1.7 eight-cell embryos/experiment (OPU) and 2.1 eight-cell embryos/experiment (OvH) were obtained after FSH + hCG stimulation vs. 1.8 eight-cell embryos/experiment (OPU) and 5.0 eight-cell embryos/experiment (OvH) following FSH-priming. These numbers include embryos obtained from both in vivo and in vitro matured oocytes. Conclusion A significantly lower developmental competence of the in vivo matured oocytes renders triggering of the in vivo maturation with hCG as a part of the currently used FSH-stimulation protocol unnecessary. In actual numbers, between 1 and 7 blastocysts were obtained following each FSH-priming. In the absence of further studies, FSH-priming appears superior to FSH + hCG stimulation in the common marmoset under current experimental settings.

Malathion, a widely used organophosphate, is known for its relatively low toxicity and extensive application. However, it has been found to act as a female reproductive toxicant by causing oxidative stress, apoptosis, autophagy, and hormonal imbalances. Hesperidin, a flavonoid belonging to the flavanone class, exhibits various beneficial properties such as antioxidant and anti-inflammatory effects, which can potentially counteract harmful effects. The objective of this study was to examine how hesperidin and malathion impact the expression of miRNAs and genes linked to apoptosis and inflammation. Balb/c mice (n = 40) were divided into four groups: hesperidin (20 mg/kg), malathion (3 mg/kg), hesperidin+malathion, and control. After a 35-day intraperitoneal treatment, the mice were sacrificed. The left ovaries were used for analyzing the expression of miRNA-146a-5p, miRNA-129-3p, miRNA-96-5p, NF-κB, Bax, and Bcl-2 through RT-qPCR, as well as the levels of several cytokines using the ELISA method. The right ovaries were examined through histological and immunohistochemical techniques using H&E and NF-κB staining. Malathion exposure led to an increased Bax/Bcl-2 ratio, upregulated expression of Bax and NF-κB, elevated levels of IFN-γ, IL-2, and IL-6, enhanced expression of miRNA-146a-5p, decreased expression of miRNA-129-3p and miRNA-96-5p, and reduced levels of IL-4 and IL-10. Additionally, malathion-exposed ovaries exhibited structural abnormalities and disrupted architecture, accompanied by heightened NF-κB immunoreactivity. Conversely, treatment with hesperidin showed its capacity to counteract the detrimental consequences of malathion on the ovaries by alleviating or reversing these changes. In conclusion, hesperidin showed protective effects against malathion-induced ovarian toxicity by modulating cytokine production, apoptosis, inflammation, and miRNA expression.

Aim – to study the dynamics of ovarian parameters in women from the first period of adulthood to early old age measured by sonography. Material and methods. The study used the results of an ultrasound examination of 81 women with normal pelvic dimensions, without reproductive organ pathology, having maximum two pregnancies in life history more than one year before the study. All participants gave their consent to routine examination. The procedure consisted of measuring the length, width, anteroposterior size and volume of the ovaries by transvaginal access according to standard protocols. The subjects were divided into three groups according to anatomical age classification. The first group consisted of 29 early adulthood women (22 to 35 years); the second group included 23 women in middle adulthood (36 to 56 years) and 29 early old age women (57 to 73 years). Results. All the ovarian parameters decreased by early old age (p 0.01). At the same time, a trend towards macroanatomic asymmetry of the ovaries with larger dimensions in the right side was revealed in each of the studied age periods (p 0.05). Conclusion. The results of a lifetime comparative analysis of the anatomical dimensions of the ovaries in women contribute to the knowledge of their age-specific structure and requires a future detailed study. A new knowledge is required to develop modern methods for preventing pathologies of the female reproductive system and to provide timely, high-quality medical care.