Search Results (541)

Leptin (LEP) is an adipocyte-derived cytokine that integrates nutritional status, metabolism, and reproduction in cattle, with particular relevance for modern high-producing dairy cows. In ruminants, LEP and its receptors are widely expressed in metabolic and reproductive tissues, including adipose tissue, liver, hypothalamus, pituitary, ovary, uterus, and placenta, where LEP modulates energy homeostasis, neuroendocrine function, and local tissue responses. Changes in circulating LEP concentrations during the transition period reflect changes in body fat reserve, insulin and GH-IGF-1 dynamics, thyroid hormones, and inflammation and contribute to coordinated metabolic adaptations supporting the onset of lactation. At the reproductive level, LEP influences the hypothalamic–pituitary–gonadal axis, affects the pulsatility of luteinizing hormone (LH) under nutritional stress, and exerts direct effects on ovarian steroidogenesis, folliculogenesis, oocyte competence, embryo development, and uterine immune function. New evidence also links LEP profiles to major peripartum disorders, including subclinical ketosis, insulin resistance, postpartum ovarian inactivity, and uterine inflammatory diseases, and emphasises its potential as part of a panel evaluating the risk of metabolic and reproductive disorders. Furthermore, polymorphisms within the bovine LEP gene and its signalling network have been associated with milk production, feed efficiency, body condition, and fertility traits, suggesting opportunities to incorporate markers into genomic selection schemes aimed at improving robustness and reproductive performance. This review summarises current knowledge on LEP biology in cattle, with an emphasis on dairy cows, and discusses perspectives on translating this information into practical tools for nutritional management, health monitoring, and genetic improvement in bovine production systems. Full article

Ovarian tissue cryopreservation (OTC) has emerged as the only viable fertility preservation strategy for prepubertal girls and adolescent cancer patients facing gonadotoxic treatments. While OTC has transitioned from an experimental procedure to an established clinical practice, the functional longevity of transplanted grafts remains limited by massive follicle depletion. This review synthesizes recent technological advances in OTC for female children, with a particular focus on the underlying molecular mechanisms and innovative protective strategies. We systematically evaluate pre-cryopreservation assessments, surgical harvesting techniques such as medulla-sparing biopsies, and the comparative efficacy of slow freezing versus vitrification in preserving stromal and follicular integrity. Central to this discussion are the molecular drivers of post-transplantation injury, including ischemia–reperfusion-induced oxidative stress and the iatrogenic over-activation of the PI3K/Akt/mTOR signaling pathway, which leads to follicular “burnout.” Furthermore, we explore targeted pharmacological interventions, such as the dual-drug application of VEGFA and rapamycin, alongside emerging bioengineering frontiers including decellularized extracellular matrix scaffolds and 3D-printed bioprosthetic ovaries. Clinical outcomes are also summarized, highlighting high rates of endocrine recovery (~95%) and promising live birth rates (~28%), predominantly through natural conception. By integrating deep molecular insights with advanced tissue engineering, this review provides a comprehensive framework for optimizing long-term fertility restoration and improving the quality of survivorship for young female cancer survivors. Full article

Intermittent fasting (IF) has emerged as a popular dietary intervention with potential metabolic and endocrine benefits. However, its effects on sexual function and reproductive health remain incompletely understood. This comprehensive review synthesizes current evidence from human clinical trials and animal studies examining the impact of various IF protocols—including time-restricted eating (TRE), alternate-day fasting (ADF), and Ramadan fasting—on male and female sexual function, reproductive hormones, and fertility outcomes. In males, limited human data suggest preserved erectile function but reduced sexual desire during Ramadan fasting, with neutral effects on testosterone in obese adults undergoing TRE. Animal studies demonstrate context-dependent effects, with IF protecting against high-fat diet-induced reproductive dysfunction while potentially impairing spermatogenesis under prolonged energy restriction. In females, IF shows promise for improving hyperandrogenism and menstrual regularity in polycystic ovary syndrome (PCOS), mediated by enhanced insulin sensitivity and reduced free androgen index. However, direct measurements of female sexual function domains (libido, arousal, lubrication, orgasm) are largely absent from the literature. Mechanistic pathways involve modulation of the hypothalamic–pituitary–gonadal (HPG) axis, insulin–adipokine signaling, sex hormone-binding globulin (SHBG), and oxidative stress pathways. Evidence quality is limited by small sample sizes, heterogeneous protocols, short follow-up periods, and predominance of animal data. While IF may offer reproductive benefits in metabolically compromised populations, particularly women with PCOS, caution is warranted in young, lean, or energy-deficient individuals. Future research should employ standardized IF protocols, validated sexual function instruments, and long-term fertility endpoints to establish evidence-based clinical recommendations. Full article

In the female organism, Anti-Müllerian hormone (AMH) is produced exclusively by granulosa cells, particularly in secondary and early tertiary follicles. The amount of AMH released into the blood is proportional to the total number of follicles present in the ovaries and is therefore used to estimate the ovarian functional reserve. In both cattle and mares, a strong and highly repeatable association has also been demonstrated between AMH concentrations and antral follicle count. Therefore, AMH may serve as a biomarker with broad diagnostic utility in reproductive medicine in these species, as it reflects the functional ovarian reserve through its association with viable antral and preantral follicles. While AMH is already being used for clinical diagnostics in human reproductive medicine and has been extensively investigated, it has received little attention in applied veterinary practice so far. This review explores the applications of AMH for reproductive medicine in cattle and horses, monoovulatory farm animals in which assisted reproductive technologies are widely used. The objectives of this review are to (I) provide clinically relevant background information and a comparative discussion of (II) the role of AMH in follicular development, (III) its value as a fertility indicator, and (IV) its significance for embryo production in vivo and in vitro in cows and mares, with particular emphasis on practical relevance and potential applications. Full article

The present study investigated the effects of propionic acid (PA) supplementation during the in vitro growth of oocytes derived from bovine early antral follicles (EAFs) on oocyte quality and granulosa cell (GC) characteristics. Oocyte–GC complexes (OGCs) were collected from bovine ovaries and cultured for 14 days in medium supplemented with or without 0.01 mM PA. Oocytes and GCs obtained from large antral follicles were used as in vivo controls. Oocytes cultured with PA exhibited higher nuclear maturation and fertilization rates than those cultured without PA. PA supplementation increased lipid content and ATP levels in both oocytes and GCs and enhanced glucose consumption in OGCs. However, compared with in vivo-grown oocytes, in vitro-grown oocytes showed lower ATP levels, lipid content, mitochondrial membrane potential, and fertilization ability. RNA-seq followed by K-medoids clustering analysis revealed that PA-induced genes in GCs showing expression patterns similar to those in vivo were mainly associated with oxidative phosphorylation, whereas genes showing expression patterns distinct from the in vivo profile were associated with the PI3K–Akt signaling pathway. In conclusion, PA improves the quality of in vitro-grown oocytes and is associated with enhanced energy status in both oocytes and GCs. However, some PA-induced gene expression patterns in GCs differed from those observed in vivo. Full article

The anti-Müllerian hormone type II receptor (Amhr2) is a critical component of the transforming growth factor-β (TGF-β) signaling pathway and plays essential roles in sex determination and gonadal development in teleosts. However, its function in the blotched snakehead (Channa maculata), an economically important fish in China, remains unexplored. In this study, we cloned and characterized the Amhr2 ortholog from C. maculata, designated CmAmhr2. The gene encodes a 443-amino acid protein containing a conserved STYKc kinase domain. Sequence and phylogenetic analyses revealed that CmAmhr2 is homologous to autosomal Amhr2 in other teleosts. Spatiotemporal expression analyses showed that CmAmhr2 was predominantly expressed in testes, particularly during critical windows of gonadal differentiation. In situ hybridization localized CmAmhr2 transcripts mainly in spermatogonia, with weaker signals in primary spermatocytes, Sertoli cells, and early-stage oocytes (oogonia and primary oocytes). Dietary administration of 30 mg/kg 17β-estradiol (E₂) from 15 to 45 days post-fertilization (dpf) for 30 days induced male-to-female sex reversal, producing neofemales (XY-F) and intersex individuals (XY-I). CmAmhr2 expression levels progressively declined with the degree of gonadal feminization: highest in normal XY male (XY-M) testes, intermediate in XY-I ovotestes, and lowest in fully feminized XY-F and normal XX female (XX-F) ovaries. Furthermore, CRISPR/Cas9-mediated mutagenesis of CmAmhr2 generated frameshift mutations predicted to disrupt the kinase domain. These findings suggest that CmAmhr2 is involved in male sex differentiation and testis development in C. maculata, providing novel molecular insights and a foundation for future sex-control research in aquaculture. Full article

Incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have emerged as potentially promising therapeutic agents for improving ovarian function, especially in women with polycystic ovary syndrome (PCOS) and obesity-related reproductive dysfunction. This comprehensive review synthesizes evidence from 30 highly relevant studies examining the mechanisms of action, clinical outcomes, and safety profile of incretin therapies on ovarian function. The evidence suggests that GLP-1 RAs may exert beneficial effects through multiple molecular pathways, including FOXO1 signaling, modulation of steroidogenesis, and enhancement of insulin sensitivity, although most mechanistic data derive from animal models and in vitro studies without validation in human ovarian tissue. Clinical outcomes from randomized controlled trials and meta-analyses show improvements in menstrual regularity, hormonal profiles, and spontaneous conception rates, though evidence certainty is limited by small sample sizes, short duration, high heterogeneity, and restriction to overweight/obese populations. While preliminary safety data regarding inadvertent early pregnancy exposure are reassuring, animal studies suggest potential dose-dependent risks that warrant careful consideration. Importantly, GLP-1 RAs are not currently approved or guideline-recommended for fertility restoration, and substantial uncertainty remains regarding long-term reproductive safety, optimal patient selection, and clinical guidelines. This review provides a balanced synthesis of current evidence and identifies critical gaps requiring further investigation before routine clinical use can be recommended. Full article

Introduction: Talc, commonly used in products like baby powder and cosmetics, has been studied for a possible link to female genital cancers, especially ovarian cancer. However, evidence is inconclusive. We conducted a systematic review and meta-analysis to assess the association between talc exposure and the incidence and mortality of ovarian, cervical, and endometrial cancers, including ovarian cancer subtypes. Method: We searched MEDLINE (PubMed) and SCOPUS databases up to January 2026 for cohort and case–control studies. Studies were assessed for quality using a modified Newcastle–Ottawa Scale. Due to the nature of available data, meta-analysis was performed only on case–control studies on ovarian cancer, using a random-effects model. Publication bias was assessed through funnel plots and Egger’s test, and a leave-one-out sensitivity analysis was performed. Stratified analyses were conducted based on geographic location, year of publication, exposure source, and tumor characteristics. Additionally, a two-stage dose–response meta-analysis was performed for ovarian cancer regarding frequency and duration of talc use. Results: Our review identified 37 studies related to ovarian cancer, one to cervical cancer, and six to endometrial cancer. Twenty-five case–control studies were included in the meta-analysis. Results showed a positive association between talc use and ovarian cancer risk (RR 1.32; 95% CI: 1.25–1.39), with stronger associations observed for women who applied talc directly to the genital area (RR 1.38) and those who used talc after bathing (RR 1.30). The risk was also higher for specific ovarian cancer subtypes, such as serous (RR 1.36) and endometrioid tumors (RR 1.35). No evidence of publication bias was found. Results of the pooled analysis of four cohort studies showed no association (RR for ever-use 1.08; 95% CI: 0.99–1.17, no trend according to duration or frequency of use). For cervical and endometrial cancers, no significant associations with talc exposure were observed. Conclusions: Case–control studies suggest a modest link between genital talc use and ovarian cancer risk, especially serous and endometrioid types. Cohort studies show no association, and no links were found for cervical or endometrial cancers. Accordingly, the results should be interpreted with caution, and the current evidence does not conclusively establish a causal relationship. Full article

Nerve Growth Factor (NGF), a member of the neurotrophin family, is currently regarded as a key regulator of ovarian physiology beyond its well-known neurotrophic functions. The mammalian ovary is one of the most highly innervated peripheral organs. Increasing evidence indicates that NGF and its receptors, TrkA and p75NTR, are widely expressed in ovarian tissues. Through the activation of the PI3K/AKT, MAPK/ERK, and PLCγ signaling pathways, NGF influences granulosa cell proliferation, steroidogenesis, and ovulation. Physiological levels of NGF are essential for primordial follicle activation, FSH receptor expression, and effective bidirectional communication between oocytes and surrounding somatic cells. As a result, NGF also regulates oocyte maturation and developmental competence. The disruption of NGF signaling can lead to serious health issues. Both low and high levels of NGF negatively affect folliculogenesis and fertility. Elevated intraovarian NGF results in sympathetic over-innervation, altered steroid production, and polycystic ovarian features. In addition, increased NGF expression has been linked to endometriosis and ovarian cancer progression. Clinical studies further suggest that follicular NGF levels may serve as indicators of ovarian reserve and reproductive outcomes in assisted reproduction. This narrative review synthesizes the current knowledge on NGF roles in ovarian physiology and disease. It highlights NGF’ dual functions as a central regulator of follicular dynamics, and as a potential biomarker and therapeutic target for common reproductive system diseases. Full article

Background: Although ovarian cryopreservation is an essential strategy for fertility preservation, ischemia–reperfusion injury and oxidative stress can significantly compromise graft viability after transplantation. Melatonin is a potent antioxidant capable of modulating redox homeostasis and tissue repair; however, its effects on the ovarian microenvironment after cryopreservation are not fully understood. Objective: To investigate whether melatonin supplementation during ovarian cryopreservation enhances GPx1/2-mediated antioxidant defense, preserves follicular integrity, and modulates the angiogenic balance (assessed via VEGF-A expression) after autologous ovarian transplantation in rats. Methods: Twenty-four Wistar rats were ovariectomized and divided into control (standard cryopreservation) and melatonin-treated (0.1 μM melatonin) groups. Ovaries were cryopreserved, thawed, and autotransplanted. After 30 days, the grafts were analyzed for GPx1/2 expression (immunohistochemistry), VEGF-A levels (ELISA), biochemical markers, and follicular integrity (histomorphometry) Results: The melatonin treatment significantly increased GPx1/2 expression in the corpus luteum (p = 0.002), theca interna (p = 0.007), and interstitium (p = 0.012), and reduced the number of degenerated follicles (p = 0.03). Although absolute VEGF-A levels did not differ between groups, melatonin-treated animals showed higher VEGF/FSH ratios (p = 0.0007) and VEGF/LH (p = 0.0494) ratios. Positive correlations were observed between GPx1/2 expression and VEGF-A expression. Conclusions: Melatonin increases antioxidant defenses in cryopreserved ovarian grafts through the upregulation of GPx1/2 and preservation of follicular morphology. Instead of directly increasing VEGF-A levels, melatonin appears to modulate angiogenic signaling, contributing to a more stable microenvironment for ovarian graft survival. Full article

Background and Clinical Significance: The management of large benign ovarian cysts in women of reproductive age requires balancing minimally invasive surgery with oncologic safety and preservation of ovarian function. Laparoscopic cystectomy for large cysts is technically challenging and carries an increased risk of intraoperative rupture and spillage; Case Presentation: We describe a novel hybrid laparoscopic–extracorporeal technique in which controlled cyst decompression is performed using a balloon-tipped trocar through a suprapubic port under direct laparoscopic visualization. The ovary is then carefully mobilized and exteriorized through the same incision, allowing extracorporeal cystectomy and ovarian reconstruction before returning the adnexa to the abdominal cavity. This approach was applied in a series of six patients with large benign-appearing ovarian cysts, including one 42-year-old patient with an 18 cm multilocular mature cystic teratoma. There were no intraoperative or postoperative complications, no conversions to laparotomy, and all patients were discharged on postoperative day 1. Follow-up at six weeks and subsequent imaging at nine months demonstrated preserved ovarian architecture, normal menstrual function, and high patient satisfaction; Conclusions: The hybrid laparoscopic–extracorporeal approach appears feasible and may offer a safe surgical option in carefully selected patients, allowing fertility preservation while minimizing the risk of spillage. Further studies are needed to evaluate reproducibility, oncologic safety, and long-term reproductive outcomes. Full article

Background: Fertility preservation aims to maintain reproductive potential in patients undergoing potentially gonadotoxic treatments, increasingly relying on centralized cryobanks requiring ovarian tissue transport. Ovarian tissue cryopreservation is a widely implemented, evidence-based procedure for young women (age 18–35) with a regular ovarian reserve. The ovaries of patients are typically transported overnight to a centralized cryobank for freezing and storage, using a certified hypothermic organ preservation solution such as histidine-tryptophan-ketoglutarate (HTK) at 4–8 °C. The molecular effects of transport on ovarian tissue remain unclear. Methods: In this prospective study of 36 breast cancer patients, we compared whole-transcriptome RNA (RNA-seq) expression in 18 frozen–thawed ovarian biopsies after overnight hypothermic transport followed by slow-freezing versus 18 direct slow-freezing within ≤2 h under FertiPROTEKT-standard conditions. Results: The RNA-seq analysis identified 6 significantly upregulated genes (Bonferroni < 0.05, fold change > 1.5), including histone H2B and mitochondrial NADH dehydrogenase subunit 6 (MT-ND6). The small number of differentially expressed genes suggests only limited transcriptional changes between the two transport conditions. H2B upregulation was confirmed by qPCR, while MT-ND6 showed only moderate levels in RNA-seq but remained stable in qPCR. Immunohistochemical analysis confirmed protein presence and localization in formalin-fixed tissue from four samples, constituting, to our knowledge, the first report of MT-ND6 protein expression in human ovarian tissue. Conclusions: Overall, these results are consistent with subtle changes in chromatin organization and mitochondrial energy metabolism. Since RNA-seq revealed only modest differences in gene expression, with no appreciable up- or downregulation of apoptosis- or damage-related genes after ≤24 h, this indicates tissue stability under the studied combined conditions (transport + cryopreservation). These findings are consistent with the feasibility of the workflow under the studied conditions of centralized ovarian tissue cryobanking combined with overnight transportation and hypothermic HTK solution. Full article

Ovarian tissue cryopreservation is the primary fertility preservation strategy for prepubertal girls and patients requiring urgent gonadotoxic therapy. However, the risk of reintroducing malignant cells has prompted the development of safer alternatives, including follicle isolation followed by three-dimensional scaffold encapsulation for transplantation. Fibrin is a promising biomaterial for bioengineered ovary construction, although its ability to support early human follicle maintenance remains unclear. Follicles isolated from cryopreserved ovarian tissues of six patients were encapsulated within fibrin scaffolds of graded concentrations (high, medium, low). After 7 days of in vitro culture, follicle survival and diameter change were quantified. A total of 282 follicles (45.4 ± 10.1 µm) were embedded into fibrin scaffolds. After culture, 237 viable follicles were detected, yielding an overall survival of 84%. Follicle diameter increased to 58.8 ± 12.0 µm. Follicle survival rates were comparable across groups, while mean follicle diameter was 56.3 ± 12.5 µm (high), 61.9 ± 13.4 µm (medium), and 57.4 ± 9.3 µm (low). Follicles cultured in medium-concentration fibrin demonstrated significantly larger diameters compared with both high and low groups (p < 0.05), with no difference between high and low groups. Fibrin-based bioprosthetic ovary scaffolds support short-term in vitro maintenance of isolated human follicles, preserving spherical morphology and granulosa cell layer integrity. Medium-concentration fibrin was associated with greater follicle diameter expansion compared with higher and lower concentrations, indicating that scaffold composition influences early morphometric changes during in vitro follicle culture. Full article

Congenital anomalies of the reproductive system represent a heterogeneous group of structural and functional abnormalities affecting both male and female genital organs. These anomalies typically arise during embryogenesis and may remain asymptomatic until they are incidentally identified during evaluation for infertility, recurrent pregnancy loss, or disorders of sexual development. In females, abnormalities include Müllerian duct anomalies and congenital malformations of the uterus, cervix, vagina, and ovaries, such as Mayer–Rokitansky–Küster–Hauser syndrome, septate, unicornuate, bicornuate, and didelphys uteri, and ovarian agenesis and undescended ovaries. In males, congenital conditions such as anorchia, cryptorchidism, hypospadias, ejaculatory duct obstruction, and ejaculatory dysfunction may be associated with impaired spermatogenesis and reduced fertility. Early recognition of these conditions may facilitate timely clinical evaluation and individualized management, which can include surgical correction, hormonal therapy, and reproductive counseling. When appropriate, early diagnosis may support multidisciplinary care, with the aim of optimizing sexual development, preserving reproductive potential, and reducing long-term morbidity associated with congenital anomalies. However, the clinical impact of early detection varies depending on the type and severity of the anomaly. A systematic and multidisciplinary approach may contribute to improved reproductive outcomes and better overall reproductive health in affected individuals. Further research is needed to better define the optimal timing and clinical utility of systematic evaluation strategies in this patient population. Full article

Polycystic ovarian syndrome (PCOS) is a complex endocrine and metabolic disorder that affects reproductive health, metabolic function, and long-term cardiovascular health in women of reproductive age. The syndrome is characterized by hyperandrogenism, chronic anovulation, insulin resistance, oxidative stress, and ovarian microenvironment remodeling. While current treatments focus on symptom relief through hormone regulation, insulin sensitizers, or ovulation induction, there is a need to target the underlying molecular and cellular processes that drive disease progression and infertility. Breakthroughs in reproductive and metabolic medicine have led to the development of next-generation therapeutics for PCOS that aim to restore ovarian function at the molecular level. Nanoparticle- and nanofiber-based drug delivery systems offer targeted delivery to the ovaries, improved bioavailability, and controlled release of insulin sensitizers, antioxidants, and anti-androgens. Metabolic reprogramming strategies that target insulin resistance, mitochondrial dysfunction, and autophagy have emerged as potential disease-modifying interventions. In addition, AI-enabled precision medicine approaches are reshaping PCOS management through phenotype-based classification, predictive modeling, and personalized fertility optimization. In this review, we highlight recent advancements in understanding the molecular pathophysiology of PCOS and introduce novel therapeutics that harness intelligent drug delivery, ovarian microenvironment restoration, and AI-based interventions. We discuss the potential of these innovative strategies to update PCOS management options for long-term ovarian restoration and fertility. Full article