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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]

In fish species, there is limited analysis of signature transcriptome profiles at the single‐cell level in gonadal cells. Here, the molecular signatures of distinct ovarian cell categories in adult Nile tilapia (Oreochromis niloticus) were analysed using single‐nucleus RNA sequencing (snRNA‐seq). We identified four cell types (oogonia, oocytes, granulosa cell, and thecal cell) based on their specifically expressed genes and biological functions. Similarly, we found some key pathways involved in ovarian development that may affect germline–somatic interactions. A cell‐to‐cell communication network between the distinct cell types was constructed. We found that the bidirectional communication is mandatory for the development of germ cells and somatic cells in fish ovaries, and the granulosa cells and thecal cells play a central regulating role in the cell network in fish ovary. Additionally, we identified some novel candidate marker genes for various types of ovarian cells and also validated them using in situ hybridization. Our work reveals an ovarian atlas at the cellular and molecular levels and contributes to providing insights into oogenesis and gonad development in fish. [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]

STUDY QUESTION Is oocyte developmental competence associated with changes in granulosa cell (GC) metabolism? SUMMARY ANSWER GC metabolism is regulated by the LH surge, altered by obesity and reproductive aging, and, in women, specific metabolic profiles are associated with failed fertilization versus increased blastocyst development. WHAT IS KNOWN ALREADY The cellular environment in which an oocyte matures is critical to its future developmental competence. Metabolism is emerging as a potentially important factor; however, relative energy production profiles between GCs and cumulus cells and their use of differential substrates under normal in vivo ovulatory conditions are not well understood. STUDY DESIGN, SIZE, DURATION This study identified metabolic and substrate utilization profiles within ovarian cells in response to the LH surge, using mouse models and GCs of women undergoing gonadotropin-induced oocyte aspiration followed by IVF/ICSI. PARTICIPANTS/MATERIALS, SETTING, METHODS To comprehensively assess follicular energy metabolism, we used real-time metabolic analysis (Seahorse XFe96) to map energy metabolism dynamics (mitochondrial respiration, glycolysis, and fatty acid oxidation) in mouse GCs and cumulus–oocyte complexes (COCs) across a detailed time course in the lead up to ovulation. In parallel, the metabolic profile of GCs was measured in a cohort of 85 women undergoing IVF/ICSI (n = 21 with normal ovarian function; n = 64 with ovarian infertility) and correlated with clinical parameters and cycle outcomes. MAIN RESULTS AND THE ROLE OF CHANCE Our study reveals dynamic changes in GC energy metabolism in response to ovulatory LH, with mitochondrial respiration and glycolysis differentially affected by obesity versus aging, in both mice and women. High respiration in GCs is associated with failed fertilization (P  <   0.05) in a subset of women, while glycolytic reserve and mitochondrial ATP production are correlated with on-time development at Day 3 (P  <   0.05) and blastocyst formation (P  <   0.01) respectively. These data provide new insights into the cellular mechanisms of infertility, by uncovering significant associations between metabolism within the ovarian follicle and oocyte developmental competence. LIMITATIONS, REASONS FOR CAUTION A larger prospective study is needed before the metabolic markers that were positively and negatively associated with oocyte quality can be used clinically to predict embryo outcomes. WIDER IMPLICATIONS OF THE FINDINGS This study offers new insights into the importance of GC metabolism for subsequent embryonic development and highlights the potential for therapeutic strategies focused on optimizing mitochondrial metabolism to support embryonic development. STUDY FUNDING/COMPETING INTEREST(S) National Health and Medical Research Council (Australia). The authors have no competing interests. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Phthalates are used as plasticizers and solvents in consumer products. Virtually 100% of the US population has measurable exposure levels to phthalates, however, the mechanisms by which prenatal exposure to phthalate mixtures affects reproductive health in the offspring remain unclear. Thus, this study tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture promotes inflammation in F1 ovarian tissue. Pregnant CD-1 dams were dosed orally with vehicle control (corn oil) or phthalate mixture (20 μg/kg/d, 200 μg/kg/d, 200 mg/kg/d, 500 mg/kg/d). Pregnant dams delivered pups naturally and ovaries and sera from the F1 females were collected at postnatal day (PND) 21, PND 60, 3 mo, and 6 mo. Sera were used to measure levels of C-reactive protein (CRP). Ovaries and sera were used for cytokine array analysis. RNA was isolated from F1 ovaries and used to quantify expression of selected cytokine genes. Prenatal exposure to the mixture significantly increased the levels of CRP at 200 µg/kg/d on PND 21 compared with controls. The mixture altered 6 immune factors in sera at PND 21 and 33 immune factors in the ovary and sera at 6 mo compared with controls. The mixture increased ovarian expression of cytokines at PND 21 and decreased ovarian expression of cytokines at 6 mo compared with controls. These data suggest that prenatal exposure to a phthalate mixture interferes with the immune response in F1 female mice long after initial exposure. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the expression patterns of secreted frizzled-related protein 5 (SFRP5) in the ovaries of Hu sheep and to explore the key downstream factors of SFRP5 in sheep granulosa cells (GCs) using RNA-seq. In the present study, SFRP5 was widely expressed in the ovary and localized to GCs and oocytes during various stages of follicular development. In addition, the expression of SFRP5 increased with follicular diameter. In contrast to the negative control, SFRP5 knockdown promoted the EdU-positive cell rate with an increase in PCNA mRNA and protein levels, whereas SFRP5 overexpression had the opposite effect. In addition, the cell cycle was propelled from the G0/G1 phase to the S phase with the upregulation of CCNB1, CCND1, CDK1, and CDK4 after SFRP5 knockdown. Moreover, SFRP5 overexpression enhanced the apoptosis of GCs with increased Caspase3 protein levels. Following SFRP5 knockdown, differentially expressed genes were mainly enriched in the PI3K/AKT, MAPK, Wnt, and Hippo signaling pathways, and several related candidate genes such as MMP1 , MMP3 , SFRP4 , INHA , TGFA , and CASP3 were screened. In general, this study enhances our understanding of the expression of SFRP5 in the GCs of Hu sheep, along with its functions in follicular development. • SFRP5 was widely expressed in different stages of follicular development of Hu sheep. • SFRP5 can inhibit and promote GCs proliferation and apoptosis, respectively. • SFRP5 regualated GCs function and state by PI3K/AKT, MAPK, Wnt, Hippo signaling pathways. [ABSTRACT FROM AUTHOR]

Mesonephric-like adenocarcinoma is a rare neoplasm of the uterine corpus and ovary. Unlike prototypical mesonephric adenocarcinoma of the uterine cervix, which is considered of Wolffian origin, recent evidence suggests that mesonephric-like adenocarcinoma is a Mullerian tumor associated with endometriosis. We report here on a 48-year-old woman with a mixed carcinoma of the ovary that consisted of mesonephric-like adenocarcinoma, clear cell carcinoma, and endometrioid carcinoma, arising from an endometriotic cyst. The mesonephric-like adenocarcinoma consisted of cuboidal cells with vesicular nuclei presenting with a tubular, ductal, papillary, and solid architecture forming nodules. Each component showed distinct immunophenotypes that were consistent with their morphology. The mesonephric-like adenocarcinoma showed diffuse positive staining for paired box 8 and GATA binding protein 3, and negative staining for estrogen and progesterone receptors. A p53 stain exhibited wild-type immunoreactivity. A complete loss of AT-rich interactive domain-containing protein 1A (ARID1A) expression was suggestive of an ARID1A mutation. Manual macrodissection and Sanger sequencing revealed identical KRAS and PIK3CA mutations in all three components. To the best of our knowledge, this is the first report of mesonephric-like adenocarcinoma combined with a clear cell carcinoma and endometrioid carcinoma, which supports the hypothesis that mesonephric-like adenocarcinoma is an endometriosis-associated neoplasm. The report also highlights a potential pitfall in diagnosing mesonephric-like adenocarcinoma combined with clear cell carcinoma. [ABSTRACT FROM AUTHOR]

This study aimed to apply the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR), the Ovarian-Adnexal Reporting and Data System (O-RADS) and contrast-enhanced ultrasound (CEUS) in an identical cohort of Chinese patients and to analyze their performance in discrimination of ovarian masses with solid components. This was a two-center retrospective study that included a total of 94 ovarian lesions in 86 women enrolled from January 2018 to February 2023. The lesions were classified by using the IOTA terminology and CEUS was performed for the lesions exhibiting solid components on ultrasonography, IOTA SR and O-RADS were applied, and CEUS images were analyzed retrospectively. We assessed the time to wash-in, time to peak intensity (PI), PI compared to myometrium, and time to wash-out, and observed statistically significant differences between benign and malignant lesions in the first three parameters. CEUS characteristics were employed to determine CEUS scores for benign (score 0) and malignant (score 3) lesions. Subsequently, the lesions were reassessed based on the IOTA SR and O-RADS classifications and CEUS scores. The sensitivity, specificity, and area under the receiver-operating-characteristics curve (AUC) of the different models were also determined. Among the 94 ovarian lesions, 46 (48.9%) were benign and 48 (51.1%) were malignant. It was found that in the 60 lesions to which the SR could be applied, the sensitivity, specificity, and AUC was 0.900, 0.667, and 0.783, respectively. The sensitivity, specificity, and AUC of O-RADS was observed to be 1.000, 0.283 and 0.641, respectively. When SR and O-RADS were combined with CEUS, their sensitivity, specificity, and AUC values were increased to 0.917, 0.891, 0.904, and 0.958, 0.783, 0.871, respectively. IOTA SR and O-RADS exhibited relatively low specificity in differentiating malignant from benign ovarian lesions with the solid components, and their diagnostic performance can be significantly improved when combined with CEUS. [ABSTRACT FROM AUTHOR]

Adipose tissues produce a variety of biologically active compounds, including cytokines, growth factors and adipokines. Adipokines are important as they function as endocrine hormones that are related to various metabolic and reproductive diseases. The goal of this review was to summarise the role of asprosin, a recently discovered adipokine, and compare its role in ovarian steroidogenesis with that of other adipokines including adiponectin, leptin, resistin, apelin, visfatin, chemerin, irisin, and gremlin 1. The summary of concentrations of these adipokines in humans, rats and other animals will help researchers identify appropriate doses to test in future studies. Review of the literature indicated that asprosin increases androstenedione production in theca cells (Tc), and when cotreated with FSH increases oestradiol production in granulosa cells (Gc). In comparison, other adipokines (1) stimulate Gc oestradiol production but inhibit Tc androgen production (adiponectin), (2) inhibit Gc oestradiol production and Tc androstenedione production (leptin and chemerin), (3) inhibit Gc steroidogenesis with no effect on Tc (resistin), (4) inhibit Gc oestradiol production but stimulate Tc androgen production (gremlin 1), and (5) increase steroid secretion by Gc, with unknown effects on Tc steroidogenesis (apelin and visfatin). Irisin has direct effects on Gc but its precise role (inhibitory or stimulatory) may be species dependent and its effects on Tc will require additional research. Thus, most adipokines have direct effects (either positive or negative) on steroid production in ovarian cells, but how they all work together to create a cumulative effect or disease will require further research. Adipose tissues produce a variety of biologically active compounds including adipokines, which function as endocrine hormones that are linked to various metabolic and reproductive diseases. The goal of this review was to provide an up-to-date summary of the role of some of these adipokines in mammalian reproduction and how they regulate ovarian steroid production. Understanding the effects of these adipokines on ovarian function will help formulate solutions for improved reproductive efficiency. Image by Leon Spicer. [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]

Magnetic resonance imaging (MRI) is an essential tool for evaluating pelvic disorders affecting the prostate, bladder, uterus, ovaries, and/or rectum. Since the diagnostic pathway of pelvic MRI can involve various complex procedures depending on the affected organ, the Reporting and Data System (RADS) is used to standardize image acquisition and interpretation. Artificial intelligence (AI), which encompasses machine learning and deep learning algorithms, has been integrated into both pelvic MRI and the RADS, particularly for prostate MRI. This review outlines recent developments in the use of AI in various stages of the pelvic MRI diagnostic pathway, including image acquisition, image reconstruction, organ and lesion segmentation, lesion detection and classification, and risk stratification, with special emphasis on recent trends in multi-center studies, which can help to improve the generalizability of AI. [ABSTRACT FROM AUTHOR]

Ovarian cells, including oocytes, granulosa/cumulus cells, theca cells, and stromal cells, contain abundant mitochondria, which play indispensable roles in the processes of ovarian follicle development. Ovarian function is closely controlled by mitochondrial proteostasis and mitostasis. While mitochondrial proteostasis and mitostasis are disturbed by several factors, leading to dysfunction of ovarian function and initiating the mitochondrial unfolded protein response (UPRmt) and mitophagy to maintain or recover ovarian function and mitochondrial function, clear interactions between the 2 pathways in the ovary have not been fully elucidated. Here, we comprehensively summarize the molecular networks or regulatory mechanisms behind further mitochondrial research in the ovary. This review provides novel insights into the interactions between the UPRmt and mitophagy in ovarian functions. [ABSTRACT FROM AUTHOR]

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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]

Aims Methods and results Conclusions ST11 adnexal tumour is a rare, recently described malignant neoplasm that is associated with Peutz–Jeghers syndrome. It predominantly originates from the para‐adnexal soft tissues and often shows secondary involvement of the fallopian tube and ovary. STK11 adnexal tumours have a broad differential diagnosis due to their variable morphology and non‐specific immunoprofile, and diagnostic confirmation currently requires sequencing to identify an STK11 mutation. We investigate the diagnostic utility of STK11 (LKB1) immunohistochemistry (IHC) in a cohort of STK11 adnexal tumours and morphological mimics.IHC for STK11 was performed on 122 tumours, including 17 STK11 adnexal tumours and 105 morphological mimics (10 female adnexal tumours of Wolffian origin, 22 adult granulosa cell tumours, 10 juvenile granulosa cell tumours, four Sertoli–Leydig cell tumours, two Leydig cell tumours, one Sertoli cell tumour, one steroid cell tumour, four extra‐ovarian sex cord‐stromal tumours, 16 ovarian endometrioid carcinomas, eight tubo‐ovarian high‐grade serous carcinomas, five ovarian mesonephric‐like adenocarcinomas, 14 ovarian carcinosarcomas, five peritoneal malignant mesotheliomas, two pelvic plexiform leiomyomata and one ovarian solid pseudopapillary tumour). All STK11 adnexal tumours showed complete loss of cytoplasmic staining for STK11. All other tumour types showed retained cytoplasmic staining, except for one endometrioid carcinoma with mucinous differentiation which showed complete loss of STK11 expression and a high‐grade serous carcinoma with subclonal loss.STK11 is a highly sensitive and specific immunohistochemical marker for distinguishing STK11 adnexal tumour from its histological mimics, and can obviate the need for confirmatory molecular studies in the appropriate morphological context. [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]

Loss of ovarian homeostasis is associated with ovary dysfunction and female diseases; however, the underlying mechanisms responsible for the establishment of homeostasis and its function in the ovary have not been fully elucidated. Here, we showed that conditional knockout of Rab37 in oocytes impaired macroautophagy/autophagy proficiency in the ovary and interfered with follicular homeostasis and ovary development in mice. Flunarizine treatment upregulated autophagy, thus rescuing the impairment of follicular homeostasis and ovarian dysfunction in rab37 knockout mice by reprogramming of homeostasis. Notably, both the E2F1 and EGR2 transcription factors synergistically activated Rab37 transcription and promoted autophagy. Thus, RAB37-mediated autophagy ensures ovary function by maintaining ovarian homeostasis.Abbreviations: AMH: anti-Mullerian hormone; ATG: autophagy related; BECN1: beclin 1; cKO: conditional knockout; Cre: cyclization recombination enzyme; dpp: days postpartum; E2: estradiol; E2F1: E2F transcription factor 1; EBF1: EBF transcription factor 1; EGR2: early growth response 2; FSH: follicle stimulating hormone; LH: luteinizing hormone; mpp: months postpartum; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; RAB37: RAB37, member RAS oncogene family; SQSTM1: sequestosome 1; TFEB: transcription factor EB; Zp3: zona pellucida glycoprotein 3. [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]

Background Although polycystic ovary syndrome (PCOS) is a very common endocrinopathy, there are several issues related to this disorder which perplex clinicians in their everyday practice. Objective To determine the current state of knowledge among European endocrinologists concerning the full spectrum of PCOS. Methods An online survey comprising 41 items covering various aspects of PCOS diagnosis and management was distributed to members of the European Society of Endocrinology. Results A total of 505 European endocrinologists (64% females), with a mean age of 47 ± 11.6 years, participated in the survey. The Rotterdam criteria were the primary diagnostic tool for 85% of respondents. Most referrals (87.1%) occurred between ages 20 and 40 years. Twenty-five percent of physicians have access to mass spectrometry for the evaluation of androgen levels. While an extended metabolic profile was commonly employed as part of the workup, there was uncertainty regarding chronic anovulation diagnosis. Diabetes, including gestational or type 2, was recognized as a significant risk factor with universal screening irrespective of BMI status. Lifestyle modification and metformin were considered as standard interventions by all participants alongside oral contraceptives, though there was significant discrepancy in treatment duration. Conclusions The Rotterdam diagnostic criteria are widely adopted for PCOS diagnosis among European endocrinologists. The current updated survey shows an emphasis on steroid profiling as an important part of diagnostic workup and a strong position held for recognition of PCOS as a metabolic condition with potentially serious implications. Current therapy thus shifted to the demand for prioritizing lifestyle interventions and metabolic therapies, either as monotherapy or in combination with standard hormone compounds. [ABSTRACT FROM AUTHOR]

• The combined toxicity of Mo and Cd was evaluated in duck ovaries. • Mo and/or Cd led to trace element imbalance and ovarian injury. • Mo and/or Cd disturbed Th1/Th2 balance and polarized towards Th1. • Mo and/or Cd could activate ER stress-mediated necroptosis. • Mo and Cd could aggravate ovarian toxic damage. Cadmium (Cd) and excess molybdenum (Mo) pose serious threats to animal health. Our previous study has determined that Cd and/or Mo exposure can cause ovarian damage of ducks, while the specific mechanism is still obscure. To further investigate the toxic mechanism of Cd and Mo co-exposure in the ovary, forty 8-day-old female ducks were randomly allocated into four groups for 16 weeks, and the doses of Cd and Mo in basic diet per kg were as follows: control group, Mo group (100 mg Mo), Cd group (4 mg Cd), and Mo + Cd group (100 mg Mo + 4 mg Cd). Cadmium sulfate 8/3-hydrate (CdSO 4 ·8/3H 2 O) and hexaammonium molybdate ((NH 4) 6 Mo 7 O 24 ·4H 2 O) were the origins of Cd and Mo, respectively. At the 16th week of the experiment, all ovary tissues were collected for the detection of related indexes. The data indicated that Mo and/or Cd induced trace element disorders and Th1/Th2 balance to divert toward Th1 in the ovary, which activated endoplasmic reticulum (ER) stress and then provoked necroptosis through triggering RIPK1/RIPK3/MLKL signaling pathway, and eventually caused ovarian pathological injuries and necroptosis characteristics. The alterations of above indicators were most apparent in the joint group. Above all, this research illustrates that Mo and/or Cd exposure can initiate necroptosis through Th1/Th2 imbalance-modulated ER stress in duck ovaries, and Mo and Cd combined exposure aggravates ovarian injuries. This research explores the molecular mechanism of necroptosis caused by Mo and/or Cd, which reveals that ER stress attenuation may be a therapeutic target to alleviate necroptosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Throughout the individual’s reproductive period of life the ovary undergoes continues changes, including cyclic processes of cell death, tissue regeneration, proliferation, and vascularization. Tissue-resident leucocytes particularly macrophages, play a crucial role in shaping ovarian function and maintaining homeostasis. Macrophages crucially promote angiogenesis in the follicles and corpora lutea, thereby supporting steroidogenesis. Recent research on macrophage origins and early tissue seeding has unveiled significant insights into their role in early organogenesis, e.g. in the testis. Here, we review evidence about the prenatal ovarian seeding of leucocytes, primarily macrophages with angiogenic profiles, and its connection to gametogenesis. In the prenatal ovary, germ cells proliferate, form cysts, and undergo changes that, following waves of apoptosis, give rice to the oocytes contained in primordial follicles. These follicles constitute the ovarian reserve that lasts throughout the female’s reproductive life. Simultaneously, yolk-sac-derived primitive macrophages colonizing the early ovary are gradually replaced or outnumbered by monocyte-derived fetal macrophages. However, the cues indicating how macrophage colonization and follicle assembly are related are elusive. Macrophages may contribute to organogenesis by promoting early vasculogenesis. Whether macrophages contribute to ovarian lymphangiogenesis or innervation is still unknown. Ovarian organogenesis and gametogenesis are vulnerable to prenatal insults, potentially programming dysfunction in later life, as observed in polycystic ovary syndrome. Experimental and, more sparsely, epidemiological evidence suggest that adverse stimuli during pregnancy can program defective folliculogenesis or a diminished follicle reserve in the offspring. While the ovary is highly sensitive to inflammation, the involvement of local immune responses in programming ovarian health and disease remains to be thoroughly investigated. [ABSTRACT FROM AUTHOR]

In mammals, glial cell derived neurotrophic factor (GDNF) plays a critical role in the self-renewal and maintenance of spermatogonial stem cells (SSCs) in testis and oogenesis in ovary, whilst retinoic acid (RA), the key factor of meiosis initiation, can downregulate its expression. Unlike mammals, two Gdnf replication genes are widely present in teleost fishes, however, our understanding of them is still poor. In the present study, two paralogous gdnf from Nile tilapia (Oreochromis niloticus), namely as Ongdnfa and Ongdnfb , were characterized, and then their cellular expression profiles in testis and ovary and responsiveness to RA treatment at the tissue and cellular levels were investigated. In phylogenetic tree, the Gdnfa and Gdnfb from teleost fishes were clustered into two different subclasses, respectively, and then clustered with the homologs from cartilaginous fish and tetrapods, suggesting that OnGdnfa and OnGdnfb are orthologous to GDNF and paralogous to each other. Ongdnfa is expressed in Sertoli cells and Leydig cells in testis and oocytes in ovary. The expression pattern of Ongdnfb is similar to Ongdnfa. In the ex vivo testicular organ culture, RA down-regulated the expression of Ongdnfa , whereas up-regulated the expression of Ongdnfb (P < 0.05), suggesting that they have differential responsiveness to RA signaling. RA treatment of the cultured cells derived from adult Nile tilapia testis which have the expression of RA receptors (RAR), Ongdnfa and Ongdnfb further confirmed the above result. Collectively, our study suggests that Ongdnfa and Ongdnfb have non-germline expression patterns in testis and germline expression patterns in ovary; furthermore, they have differential responsiveness to RA signaling, implying that they might have differential biological functions. This study broadens and enriches our understanding of fish GDNF homologs and lays foundation for the study of their biological functions in the future. • Two paralogous gdnf (Ongdnfa and Ongdnfb) were characterized from Nile tilapia. • Ongdnfa and Ongdnfb had non-germline expressions in testis. • Ongdnfa and Ongdnfb had germline expressions in ovary. • Ongdnfa and Ongdnfb had differential responsiveness to RA treatment. [ABSTRACT FROM AUTHOR]

Purpose: The present knowledge about lymphatic drainage of the ovary is based on carcinological studies, but it has only rarely been studied under physiological conditions. However, it is one of the preferential routes of dissemination in ovarian cancer, and understanding it is therefore vital for optimal carcinological management.Our purpose was to evaluate the feasibility of an innovative technique to study the lymphatic drainage territories of the ovary using a recirculation module on the cadaveric model. Methods: We injected patent blue into the cortex of twenty "revascularised" cadaver ovaries with the Simlife recirculation model. We observed the migration of the dye live and described the drainage territories of each ovary. Results: We observed a staining of the lymphatic vessels and migration of the dye in all the subjects, systematically ipsilateral to the injected ovary. We identified a staining of the lumbo-aortic territory in 65% of cases, with a preferential lateral-caval involvement (60%) for the right ovary and lateral-aortic territory (40%) for the left ovary. A common iliac involvement was observed in only 10% of cases. In 57% of cases, the staining of the lumbo-aortic territory was associated with a staining of the suspensory ligament. The pelvic territory was involved in 50% of cases, with an external iliac staining in 25% of cases and internal in 20%. Conclusion: Our study provides for a better understanding of lymphatic drainage of the ovary using a new detection method, and allows the possibility of improving the teaching for operators with a realistic model. Continuation of this work could lead to considering more targeted and thus less morbid lymph node sampling for lymph node staging in early-stage ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Ovarian enlargement is one of several findings of pathology, including ovarian torsion. With increasing use of MRI for acute abdominal pain in children, data for normal ovary size and appearance are needed. Objective: To provide preliminary data on normal sizes of ovaries on MRI in pediatric patients. Materials and methods: This retrospective IRB-approved study included girls (5 to 17 years of age) with MRI examinations performed for indications not related to the ovaries from 2018 to 2022. For each MRI, coronal T2-weighted single shot fast spin echo and axial T2-weighted fat-saturated images were independently reviewed by three pediatric radiologists who recorded ovary visualization and ovarian linear measurements (3 planes). Ovarian volumes were calculated from linear measurements. Agreement among observers was calculated using kappa statistics and intraclass correlation coefficients. Results: A total of 181 MRIs were reviewed. The left ovary was visualized in 166–176 (92–97%) cases (R1–R3) and the right ovary was visualized in 165–174 (91–96%) cases with excellent agreement among reviewers (left: K = 0.89 [0.84–0.94], right: K = 0.85 [0.79–0.91]). Interrater class coefficient (ICC) for largest single dimension of the ovary was left: 0.83 (CI 0.79–0.87) and right: 0.85 (CI 0.81–0.89). There were significant moderate to strong correlations between ovarian volume and age (left: 0.67 [0.58–0.75], right: 0.66 [0.57–0.74]). Conclusion: The ovaries can be adequately visualized and measured on MRI with excellent inter-reader agreement. This study serves as the foundation for developing normative values for ovarian volumes by age on MRI. [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]

The present study investigated the effect of ivermectin and amitraz on the cellular architecture of vital organs of Rhipicephalus microplus. Adult female ticks were treated with lethal concentrations (LC95) of ivermectin and amitraz, and the ovaries, synganglion, and Gené’s organ were processed 48 h post treatment. In both the treatment groups, the ultra-thin sections of ovary exhibited deformed oocytes, irregular plasmic membrane and chorion layer, extensive vacuolation in the cytoplasm mainly at periphery of the cell and oocyte-pedicel junction. Marked vacuolations in the cortex and neuropile region with significant structural disorganization of the neural fibers were common alterations observed in the synganglion of ticks exposed to ivermectin and amitraz. The tissue sections of Gené’s organ revealed deformed tubular glands with severe loss of cellular limit of secretory epithelium and cytoplasmic vacuolations in the ivermectin treated ticks whereas, the alterations were comparatively less severe in amitraz exposed ticks. The cellular deformities in these vital organs probably impaired reproductive function, nerve signal transmission and metabolic activities and thus affected fecundity and survivability of the treated ticks. The findings suggested that the action of ivermectin and amitraz are not restricted to the nervous system of ticks, but also on other vital organs, ovary and Gené’s organ affecting the oviposition. The study provided insights into the development of targeted interventions for tick control strategies. [ABSTRACT FROM AUTHOR]

Isolated fallopian tube torsion (IFTT) is a rare form of adnexal torsion that is more difficult to diagnose, which may lead to delays in treatment. Our objectives were to identify clinical and radiologic factors associated with surgically-confirmed IFTT and compare them with those of patients without torsion and with adnexal torsion (AT) in a large pediatric population. We conducted a retrospective chart review of all patients who underwent surgery for suspected adnexal torsion from 2016 to 2019. Torsion was determined intraoperatively, with IFFT defined as those with only tubal but no ovarian torsion and AT defined as those with ovarian torsion, with or without involvement of the ipsilateral fallopian tube. Clinical and radiologic variables were compared between patients with IFTT and those without torsion and with AT using descriptive statistics. A previously-described composite score to predict torsion based on the presence of vomiting and adnexal volume (VVCS) was calculated for each patient. Of 291 patients who underwent surgery for suspected torsion, 168 had confirmed torsion: 33 (19.6%) IFTT and 135 (80.4%) AT. Patients with IFTT were more likely to be younger (12.8 vs. 14.2 years, P = 0.02), premenarchal (29.0% vs. 10.7%, P = 0.009), experience nausea (90.6% vs. 70.9%, P = 0.02) and vomiting (81.3% vs. 32.8%, P < 0.001), have a paratubal cyst on imaging (18.8% vs. 2.5%, P = 0.003), and have larger adnexal volume (143.3 vs. 64.9 ml, P < 0.001) than those without torsion. Higher BMI (26.6 vs. 22.9 kg/m2, P = 0.03), a paratubal cyst on imaging (18.8% vs. 1.5%, P < 0.001), presence of arterial (65.5% vs. 44.1%, P = 0.04) and venous Doppler flow (79.3% vs. 55.9%, P = 0.02), and radiologic impression indicating lack of torsion (37.9% vs. 16.8%, P = 0.04) were more common in IFTT than AT. The accuracy of the VVCS in predicting torsion for the IFFT group was 83.9%. IFTT has a similar clinical presentation to AT but with a higher likelihood of a paratubal cyst and preserved Doppler flow on imaging. IFTT should be strongly considered in patients who present with pain, nausea, and vomiting and have an adnexal mass separate from the ovary on imaging, regardless of Doppler flow. Level II. Prognosis study. • What is currently known about this topic? Isolated fallopian tube torsion (IFTT) is a rare form of adnexal torsion with minimal data on risk factors that can help diagnose this condition or differentiate it from ovarian torsion. Low preoperative suspicion for IFTT can lead to delays in treatment that can impact future fertility. • What new information is contained in this article? Our data provide robust information about IFTT that can lead to earlier diagnosis and intervention, including the importance of nausea, vomiting, and the presence of a paratubal cyst and enlarged adnexa on imaging with frequently preserved Doppler flow. [ABSTRACT FROM AUTHOR]

Chemotherapy, pelvic radiotherapy (including total body irradiation) and novel compounds used to treat children and teenagers with benign or malignant diseases can lead to impaired fertility. For prepubertal female patients at high risk of treatment-related infertility, upfront storage of ovarian tissue is increasingly being recognised as standard of care. No surgical guidelines exist to ensure best practice technique. We reviewed current UK practice to assess surgical management. A ten-item, anonymous multiple-choice survey was distributed to the lead surgeons in all paediatric centres in England/Wales undertaking ovarian procurement for cryopreservation. There are currently 18 centres in England and Wales that provide ovarian procurement for cryopreservation. Responses were received from 100% of the invited paediatric surgical oncology centres in England and Wales. 39.3% of participants stated that in their centre <10 cases of ovarian harvest are performed annually. In 32.1% of centres >20 cases are undertaken per year. In 64% of centres surgery is performed by a paediatric surgeon with interest in oncology or fertility preservation. The majority of cases were performed by a Consultant or Senior Registrar (89%). Regarding the surgical technique, 82% of respondents stated they gain access to the abdominal cavity using standard 3-port laparoscopy, 7% use single-port laparoscopy. Most frequently used energy devices for ovary/ovarian tissue resection were Ligasure™ (44%) and Harmonic Scalpel™ (18.5%). 96% of respondents perform a total oophorectomy, 1 respondent stated they perform a hemi-oophorectomy. 53% stated they place the ovary into a retrieval bag only if the ovary was too big for easy removal via the camera port, 28.5% always place it in a retrieval bag. Most surgeons use the umbilical port site for retrieval (82%). This national survey shows significant heterogeneity in the surgical management of ovarian procurement for cryopreservation. To ensure best outcomes, research into the various surgical methods is necessary to provide data for a standardised best practice approach. This is a level II evidence study. In itself, it is a national survey of specialists, which was undertaken in a prospective manner. [ABSTRACT FROM AUTHOR]

Surfactant protein A (SP-A) and Surfactant protein D (SP-D) glycoproteins play a crucial role in maintaining lung homeostasis and lung host defense. Interestingly, these proteins are also expressed in extra-pulmonary tissues, including the female genital tract. The ovarian tissue, where SP-A and SP-D expression increases with follicular development, may serve as the primary site of defense for this tissue. However, their functions in these tissues are not well understood and are currently an active area of research. Therefore, the objective of this study is to investigate the expression of SP-A and SP-D in the ovine ovary throughout the ovarian cycle using immunohistochemistry by semiquantitative intensity classification and Western blotting techniques. These findings revealed the presence of SP-A and SP-D in various compartments of the ovary, such as the follicular epithelium, granulosa cells, cumulus cells, theca cells, oocyte I, follicular fluid, and luteal cells of Graafian follicles, excluding the corpus albicans. SP-A and SP-D likely act as a first line of defense against potential pathogens that infiltrate the ovaries. Further investigation of the differential expression of SP-A and SP-D proteins in ovarian follicles will provide a basis for understanding their interactions with key proteins involved in oogenesis. [ABSTRACT FROM AUTHOR]

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Natural Nicotinamide Adenine Dinucleotide (NAD+) precursors have attracted much attention due to their positive effects in promoting ovarian health. However, their target tissue, synthesis efficiency, advantages, and disadvantages are still unclear. This review summarizes the distribution of NAD+ at the tissue, cellular and subcellular levels, discusses its biosynthetic pathways and the latest findings in ovary, include: (1) NAD+ plays distinct roles both intracellularly and extracellularly, adapting its distribution in response to requirements. (2) Different precursors differs in target tissues, synthetic efficiency, biological utilization, and adverse effects. Importantly: tryptophan is primarily utilized in the liver and kidneys, posing metabolic risks in excess; nicotinamide (NAM) is indispensable for maintaining NAD+ levels; nicotinic acid (NA) constructs a crucial bridge between intestinal microbiota and the host with diverse functions; nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) increase NAD+ systemically and can be influenced by delivery route, tissue specificity, and transport efficiency. (3) The biosynthetic pathways of NAD+ are intricately intertwined. They provide multiple sources and techniques for NAD+ synthesis, thereby reducing the dependence on a single molecule to maintain cellular NAD+ levels. However, an excess of a specific precursor potentially influencing other pathways. In addition, Protein expression analysis suggest that ovarian tissues may preferentially utilize NAM and NMN. These findings summarize the specific roles and potential of NAD+ precursors in enhancing ovarian health. Future research should delve into the molecular mechanisms and intervention strategies of different precursors, aiming to achieve personalized prevention or treatment of ovarian diseases, and reveal their clinical application value. [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]

1. The proliferation of granulosa cells is vital for the development and recruitment of hen ovarian prehierarchical follicles (PF). The RAB23 protein is a member of the Rab family, belonging to the GTPase family. This study studied the regulatory roles of the RAB23 gene in PF.2. The expression of RAB23 was significantly increased in granulosa cells (GC) during PF growth and was highest in GC at 6–8 mm diameter (p < 0.05). The RAB23 protein was mainly expressed in the GC, oocytes (OC) as well as somatic cells (SC) of the PF.3. The mRNA expression of FSHR, CCND1,CYP11A1, StAR and HSD3B1 was significantly increased in the siRNA RAB23 group (p < 0.05). Additionally, protein expression of FSHR, CCND1, CYP11A1, HSD3B1 was significantly increased (p < 0.05) after GC were transfected with RAB23-specific siRNA. Protein expression of StAR in the siRNA RAB23 group was numerically higher than that in the positive control (PC) and negative control (NC) groups. The GC proliferation rate and progesterone synthesis of the prehierarchical follicles in hen ovaries were markedly increased in vitro (p < 0.05).4.This study revealed that RAB23 might play an inhibitory role in GC proliferation and progesterone synthesis during the prehierarchical follicles development in vitro. [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]

The present study investigates the distribution and dynamics of gonadotropin-releasing hormone I (GnRH I) and bradykinin in the air-breathing catfish, Heteropneustes fossilis, in relation to the reproductive cycle. Changes in bradykinin, bradykinin B2-receptor, and ovarian GnRH I regulation were demonstrated during the reproductive cycle. The localization of GnRH I, bradykinin, and their respective receptors in the ovaries was investigated by immunohistochemistry, while their levels were quantified by slot/western blot followed by densitometry. GnRH I and its receptor were mainly localized in the cytoplasm of oocytes during the early previtellogenic phase. However, as the follicles grew larger, immunoreactivity was observed in the granulosa and theca cells of the late previtellogenic follicles. The ovaries showed significantly higher expression of GnRH I protein and its receptor during the early to mid-previtellogenic phase, suggesting their involvement in follicular development. Bradykinin and bradykinin B 2 -receptor showed a distribution pattern similar to that of GnRH I and its receptor. This study further suggested the possibility that bradykinin regulates GnRH I synthesis in the ovary. Thus, we show that the catfish ovary has a GnRH-bradykinin system and plays a role in follicular development and oocyte maturation in H. fossilis. • Catfish, Heteropneustes fossilis ovary possess GnRH I and bradykinin system. • GnRH I and bradykinin and their receptors are present in the same cell types during different phase of reproductive cycle. • GnRH I, bradykinin and their receptors were highest during previtellogenic phase which decreased in later phases. • We hypothesized bradykinin may act as a regulator of GnRH in the ovaries of H. fossilis. [ABSTRACT FROM AUTHOR]

Selection to increase body weight in poultry can hamper reproduction traits and compromise production efficiency. Thus, attention to reproduction traits is essential to improving the sustainability of breeding programs. Data from a domestic quail breeding program for meat production were used to estimate genetic parameters. We analyzed five traits: 4-week body weight, age at sexual maturity for males and females, cloacal gland area, female, and male reproductive organs weights. A multi-trait mixed model analysis with fixed effects of generation/hatch was performed, assuming environmental covariance equals zero for sex-limited traits. Heritability estimates range from low to moderate for male sexual maturity and cloacal gland area, and high for other traits. Intersexual genetic correlation for age at sexual maturity is positive, which can lead to correlated responses in the other sex. Reproductive organs weights are genetically correlated with body weight, but not significantly between sexes and nor with sexual maturity. Genetic correlations for the cloacal gland area were positive with body weight and negative with age at sexual maturity of males and females, demonstrating a potential use of this trait for selection with favorable outcomes in reproduction. The use of the cloacal gland area can be used in the same way as the scrotal circumference in mammals, improving female reproduction traits by selecting a trait recorded in males. [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]