Reproductive Function Research Articles

POMC neurons control fertility through differential signaling of MC4R in kisspeptin neurons.

Inactivating mutations in the melanocortin 4 receptor (MC4R) gene cause monogenic obesity. Interestingly, female patients also display various degrees of reproductive disorders, in line with the subfertile phenotype of Mc4r KO female mice. However, the cellular mechanisms by which MC4R regulates reproduction are unknown. Kiss1 neurons directly stimulate gonadotropin-releasing hormone (GnRH) release through two distinct populations: the Kiss1ARH neurons, controlling GnRH pulses, and the sexually dimorphic Kiss1AVPV/PeN neurons controlling the preovulatory luteinizing hormone (LH) surge. Here, we show that Mc4r expressed in Kiss1 neurons regulates fertility in females. In vivo, deletion of Mc4r from Kiss1 neurons in female mice replicates the reproductive impairments of Mc4r KO mice without inducing obesity. Conversely, re-insertion of Mc4r in Kiss1 neurons of Mc4r null mice restores estrous cyclicity and LH pulsatility without reducing their obese phenotype. In vitro, we dissect the specific action of Mc4r on Kiss1ARH versus Kiss1AVPV/PeN neurons and show that Mc4r activation excites Kiss1ARH neurons through direct synaptic actions. In contrast, Kiss1AVPV/PeN neurons are normally inhibited by MC4R activation except under elevated estradiol levels, thus facilitating the activation of Kiss1AVPV/PeN neurons to induce the LH surge driving ovulation in females. Our findings demonstrate that POMCARH neurons acting through MC4R directly regulate reproductive function in females by stimulating the 'pulse generator' activity of Kiss1ARH neurons and restricting the activation of Kiss1AVPV/PeN neurons to the time of the estradiol-dependent LH surge, and thus unveil a novel pathway of the metabolic regulation of fertility by the melanocortin system.

The Impact of COVID-19 Infection on Semen Analysis Values in Active Duty Service Members.

The COVID-19 outbreak increased concern regarding the effects of infection and the vaccines on the risk of reproductive function. The objective of this study was to determine the effects of COVID-19 virus infection on US active duty service members' semen analysis results. This retrospective cohort analysis was performed using the Medial Assessment and Readiness System at Womack Army Medical Center. It included males on active duty for any duration from January 2011 through September 2022. These males were eligible with at least 2 semen analyses documented in laboratory reports, with those with history of COVID-19 infection having analyses before and after infection. Changes in 4 laboratory semen indices were compared: semen volume (mL), sperm count per mL, sperm motility percentage, and percentage of sperm with normal morphology. The study population comprised 1,188 active duty males with at least 2 semen analyses. Cohorts were established based on COVID-19 diagnosis (n = 60) and no history of COVID-19 diagnosis (n = 1,128). There were no differences in before-and-after semen analysis values for semen volume (mL) (P = .875) and sperm count in millions per mL (P = .973). There was a 7.02% regression-adjusted reduction in the motile sperm percentage (95% confidence interval [95% CI] -12.38 to -1.652, P = .010) and a 6.03% reduction in the percentage of sperm with normal morphology associated with COVID-19 infection (95% CI -10.03 to -2.04, P = .003). Our study detected a decrease in sperm motility and morphology in a cohort of active duty service members with a history of COVID-19 infection.

No Evidence That Life History Strategies Shape Within-Body Mosaics of Ageing.

Tissues across the body may age at different rates, which creates within-body mosaic ageing. Life history strategies shape ageing patterns at the inter- and intra-specific level, but the impact of life history strategies on mosaic-ageing patterns within individuals remains unknown. Reproductive tissues in individuals selected to prioritise reproduction may age faster than somatic tissues because of increased 'wear and tear'. Alternatively, individuals that prioritise reproduction may specially protect reproductive tissues at the expense of somatic tissues to allow for increased reproductive function. Here, we used Japanese quail (Coturnix japonica) artificially selected for increased versus reduced reproductive investment (egg size) to test how reproductive strategies modulate within-body variation in ageing patterns, by measuring telomere length as an ageing biomarker in blood cells, spleen and reproductive tissue (oviduct and testis). Although there were absolute, sex-specific differences in telomere length across tissue types, we did not find evidence that an individual's reproductive strategy shapes within-body mosaics of ageing: patterns of relative telomere length in somatic and reproductive tissues were similar in individuals selected for high and low reproductive investment, respectively (i.e., no significant selection regime × tissue type interaction), and consistent strong positive correlations in telomere lengths among blood cells, spleen and reproductive tissue were observed within individuals across reproductive investment selection regimes. Our results suggest that an individual's life history strategy does not affect tissue-specific ageing rates or that 'wear and tear' and 'special protection' mechanisms might act simultaneously and cancel each other out.

Calcium Metabolism, Immunity and Reproduction in Early Postpartum Dairy Cows

Vitamin D is essential for calcium homeostasis, bone mineralization, immunity, and disease prevention. In a field study with Holstein-Friesian dairy cows, the impact of prepartum vitamin D3 treatment on early postpartum placental gene expression, focusing on calcium metabolism, feto-placental growth, and immune response, had been investigated. Eight multiparous cows were treated with 10 mL vitamin D3 (1 million IU cholecalciferol/mL) intramuscularly on day 273 of pregnancy, while eight others remained untreated and served as controls. Placental tissues were collected post-calving, and gene expression was analyzed using quantitative real-time PCR. Among 23 genes, 5 showed significant downregulation in the treated group: CaBP-9k (reduced by 88.1% from 32.80 ± 91.50 to 3.90 ± 8.54), ESR1 (reduced by 95.7% from 7.89 ± 17.87 to 0.34 ± 0.34), LHR (reduced by 96.5% from 3.75 ± 5.45 to 0.13 ± 0.17), NOD1 (reduced by 94.1% from 4.21 ± 7.00 to 0.25 ± 0.30), and TLR1 (reduced by 99.7% from 24.80 ± 61.45 to 0.07 ± 0.08). These results suggest that vitamin D3 supplementation affects key pathways related to calcium transport, reproductive function, and immune response in the bovine placenta. These molecular changes may help to explain improved calcium homeostasis and reduced postpartum complications, offering insights into how targeted nutritional interventions can enhance reproductive efficiency in high-producing dairy cows.

Aflatoxin B1-induced toxicity, oxido-inflammatory damage, and apoptosis in male rat reproductive circuitry were abrogated by co-treating with the xanthophyll-lutein and zeaxanthin.

Reproductive dysfunction is a recognised adverse effect of exposure to aflatoxin B1 (AFB1) in humans and animals. Despite the widely acknowledged health risks, exposure to AFB1 remains unavoidable. Conversely, lutein (LUT) and zeaxanthin (ZEA) are plants' potent antioxidants and anti-inflammatory agents, exhibiting promising potential for modulating inflammatory and apoptotic signalling pathways. This study aimed to investigate the effects of co-treatment with LUT/ZEA on reproductive function in rats intoxicated with AFB1. The study utilised male Wistar rats (n = 20 and n = 4 per cohort). The experimental groups included untreated controls, AFB1 (75µg/kg), LUT/ZEA (100mg/kg), and AFB1 combined with LUT/ZEA at two different doses (100mg/kg and 200mg/kg). Treatments were administered via oral gavage for 28 consecutive days. On day 29, serum samples were collected for testicular function and hormonal assays; sperm analysis was performed; and the testes, epididymis, and brain tissues were harvested for biochemical examinations. In the AFB1-only treated rats, there was a reduction in sperm motility, viability, and count, along with an increase in abnormal sperm morphology. The AFB1 group exhibited hormonal dysfunction and showed increased serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH) levels, and decreased acid phosphatase (ACP) levels, which were associated with reduced antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione (GSH), and total thiols (TSH) in the hypothalamus, epididymis, and testes, as well as elevated oxido-inflammatory mediators xanthine oxidase (XO), nitric oxide (NO), and myeloperoxidase (MPO). Additionally, there were changes in testicular tumour suppressor markers (p53), pro-apoptotic factors Bcl-2-associated X-protein (BAX; BAX/Bcl-2 ratio), and a reduction in anti-apoptotic biomarkers B-cell lymphoma 2 (Bcl-2). Co-treatment with LUT/ZEA alleviated the toxic effects of AFB1, leading to improved hormonal and testicular function, enhanced antioxidant activity, and decreased levels of oxido-inflammatory mediators and apoptosis. LUT/ZEA corrected AFB1-induced testicular dysfunction through its antioxidant, anti-inflammatory, pro-apoptotic, and anti-apoptotic properties, thereby effectively preserving testicular function and preventing testicular cell death.

HORMONE IMBALANCE AS A MANIFESTATION OF STRESS IN THE FORMATION OF OLIGOMENORRHEA IN TEENAGE GIRLS

Stress is currently the most significant factor contributing to reproductive function disorders and has become a major public health problem in the 21st century. Stress is implicated in the development of oligomenorrhea (OM), particularly in the context of the ongoing full-scale war in Ukraine. The aim of the study was to determine the characteristics of the content of steroid hormones, including stress-related hormones, in adolescent girls with OM. Materials and methods. A total of 193 girls aged 12–18 years with OM were observed and stratified into groups according to OM duration. Hormonal assessment included serum measurements of estradiol (E2), testosterone (T), cortisol (C), 17-hydroxyprogesterone (17-OH), dehydroepiandrosterone sulfate (DHEA-S), and sex steroid-binding globulin (SSBG). The ratios of C/DHEA-S and the free T index were also calculated. Written informed consent for all medical procedures was obtained from each participant or their parents/guardians. The study protocol was approved by the Bioethics and Deontology Committee of the State Institution “Institute for Children and Adolescents Health Care of the National Academy of Medical Sciences of Ukraine” (protocol No. 7 dated 25.11.2024). Statistical analysis was performed using the computer program Statgraphics Plus. Results were analyzed by one-way analysis of variance. Differences were considered significant at ρ < 0.05. Data are presented as mean ± standard deviation (SD) and frequency counts. The significance of differences between groups was assessed using Fisher’s exact test, the Wilcoxon–Mann–Whitney test, and the χ² test. The study was conducted according to the research plan entitled “Study of the mechanisms of comorbid pathology formation in adolescent girls with menstrual disorders (primary oligomenorrhea and abnormal uterine bleeding)” (state registration number: 0121U114425). Results. At OM onset, nearly 20% of participants exhibited low E2 levels. With increased disease duration (years 2–3), the proportion of adolescents with low E2 decreased while those with elevated E2 increased. E2 is known to influence reproductive potential and correlate with mood alterations; a parallel trend was observed for C. Conversely, DHEA-S levels rose with prolonged OM duration. Early in OM progression, characteristic findings include low E2, C, and DHEA-S levels, accompanied by increased C/DHEA-S ratios, suggesting diminished adaptive capacity. With extended OM duration, the proportion of girls exhibiting elevated free T, 17-OH, DHEA-S, and T/E2 ratios increased, indicative of emerging polycystic ovary syndrome (PCOS). The percentage of adolescents with elevated C/DHEA-S ratios declined, whereas low ratios became more prevalent. Significant positive correlations were observed between C and T (r = 0.31; P < 0.001), DHEA-S and C (r = 0.46; P < 0.0001), and free T and DHEA-S (r = 0.44; P < 0.0005). Conclusions. The findings do not support an association between OM development and dysregulation of adrenal–gonadal interactions, which govern menstrual function regulation and are linked to stress responses and maladaptation.

Cadmium-Induced Testicular and Spermatogonial Damage Ameliorated by Bryonia laciniosa Linn. Seeds in Wistar Rats: An Animal Study.

Cadmium (Cd) is a ubiquitous occupational pollutant that has been extensively studied for its detrimental effects on male reproductive function, primarily through the induction of oxidative stress, which compromises both sperm quality and sperm DNA integrity. This study aimed to evaluate the protective efficacy of Bryonia laciniosa Linn., a phytochemically rich medicinal plant, against cadmium-induced reproductive toxicity in Wistar rats. Twenty-four healthy adult male Wistar rats were randomly divided into four groups (n = 6 per group): a control group, a B. laciniosa extract-treated group, a Cd-treated group, and a combination group that received both Cd and B. laciniosa extract. Rats exposed to Cd exhibited significantly reduced relative testicular weights, accompanied by impaired sperm parameters and altered spermatogonial morphology. Furthermore, Cd exposure led to significantly decreased serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone compared to the other groups. Oxidative stress biomarkers revealed that Cd exposure significantly lowered the concentrations of enzymatic antioxidants, such as superoxide dismutase (SOD) and catalase (CAT), while increasing levels of malondialdehyde (MDA) in testicular tissue. Histopathological examination of testicular cross-sections revealed considerable degeneration of spermatogenic cells, characterized by necrotic atrophy and increased eosinophilic fluid discharge in the seminiferous tubules, ultimately impairing reproductive function. Morphometric analysis was conducted using light microscopy. In contrast, treatment with B. laciniosa extract significantly reduced oxidative stress and restored enzyme levels. This restoration facilitated the regeneration of primary spermatids and spermatogonial cells in the combination treatment group, which was attributed to the extract's antioxidant-rich properties, offering protection against free radical-mediated damage and mitigating Cd-induced sperm DNA damage. The observed protective effects were primarily attributed to the synergistic antioxidant activity of B. laciniosa extract.

Gut microbiota: emerging biomarkers and potential therapeutics for premature ovarian failure

Premature ovarian failure is a prevalent gynecological endocrine disorder with an increasing incidence rate each year, impacting women’s physical and mental health. The causes of POF are poorly understood, but genetic, immune, iatrogenic, environmental, and psychological factors are key contributors. Clinically, POF manifests as oligomenorrhea, amenorrhea, elevated follicle-stimulating hormone (FSH) levels, and decreased estrogen levels, leading to infertility in women. POF not only impacts reproductive function but also elevates the risk of cardiovascular diseases, osteoporosis, depression, anxiety, cognitive decline, and neurological disorders, thereby adversely affecting women’s mental health and quality of life over the long term. The gut microbiota (GM) comprises a vast and complex microbial community within the human gastrointestinal tract. GM dysregulation is closely associated with numerous human diseases, including autoimmune diseases, allergic disorders, cardiovascular diseases, cancers, and metabolic disorders. Studies have shown that GMs play a pivotal role in female reproductive health, participating in the pathogenesis of reproductive endocrine disorders through direct or indirect involvement in sex hormone regulation, stimulation of inflammatory cytokine production, modulation of immune function, metabolic homeostasis, and regulation of neurotransmitter synthesis. Recently, advancements in human microbiology have highlighted the significant interest in the connection between POF and the gut microbiome. Researching the molecular mechanisms by which GMs and their metabolites regulate the occurrence of POF opens up a new direction for studying the pathogenesis of POF. This research aims to identify an efficient, non-invasive, and accurate diagnostic method for clinical diagnosis and treatment of POF, providing novel theoretical insights and precise intervention strategies for the clinical prevention and treatment of POF.

Impact of GLP1 agonists on reproduction.

Obesity, in animals and humans, is associated with male and female reproductive dysfunction. Elucidating the mechanisms by which excessive weight impacts reproduction and proving that weight loss improves reproductive function has been difficult. Data in animals and humans demonstrate improvements in reproductive function after weight loss, achieved with or without GLP1 agonists. In preclinical studies there is evidence that GLP1 agonists have direct effects on the hypothalamus to stimulate luteinizing hormone (LH) secretion and direct beneficial effects on the gonads and the endometrium. Whether GLP-1 agonists provide an added direct beneficial effect on reproductive organs in humans, beyond the benefits mediated by weight loss, remains unclear. However, consideration of GLP1 agonists for the treatment for obesity-associated reproductive dysfunction requires caution, as any weight loss during pregnancy is associated with adverse fetal outcomes, and preclinical studies indicate fetal toxicity of the GLP1 agonist class. Here, we review the available pre-clinical and clinical evidence of the effects of GLP-1 agonists on human reproductive health, suggest a therapeutic strategy, and list the needs for future research.

The roles of MAPK signaling pathway in ovarian folliculogenesis.

Ovarian folliculogenesis is a complex biological process critical for female fertility, intricately regulated by various signaling pathways, among which the Mitogen-Activated Protein Kinase (MAPK) signaling pathway plays a pivotal role. This review provides a comprehensive overview of the physiological functions of MAPK signaling in key stages of folliculogenesis, including primordial follicle formation and activation, dominant follicle selection, cumulus-oocyte complex (COC) expansion, ovulation, and luteinization. The orchestrating roles of MAPK on steroidogenesis and ovarian cell death are also delineated, highlighting its essential contributions to normal reproductive function. Furthermore, we explore the implications of dysregulated MAPK signaling in ovarian aging, primary ovarian insufficiency (POI), polycystic ovary syndrome (PCOS), and ovarian hyperstimulation syndrome (OHSS). By elucidating the multifaceted roles of MAPK signaling in ovarian biology, this review aims to enhance our understanding of folliculogenesis and its associated pathologies, paving the way for future research and therapeutic interventions targeting MAPK pathways in reproductive health. Clinical trial number Not applicable.

Considerations of Fertility in Elite Sportswomen: A Narrative Review.

Increasingly more women are participating in professional and recreational sports. Whilst vigorous intensity physical activity is considered beneficial, evidence demonstrates higher rates of menstrual disturbance in elite athletes. There is less clear evidence on the impact of elite-level exercise on fertility outcomes. It is critical to understand this given the optimal age for fertility is likely to coincide with the age of peak performance for many athletes. To perform a narrative review summarising the impact of elite-level exercise on reproductive function and fertility outcomes, highlighting the importance of relative energy deficiency in sport (REDs). Additionally, to outline the reproductive options for female athletes and summarise the fertility treatment outcomes and challenges for athletes. A literature search of Medline, Embase, Google Scholar and Web of Science was performed. There is clear evidence that elite-level training causing increased risk of menstrual disturbance. This is likely due to REDs, with evidence that increasing energy intake can improve menstrual dysfunction. Whilst there is limited data in athletes, data from the general population suggests exercise may be beneficial for both fertility and assisted reproduction outcomes up to a certain point, beyond which there may be a negative impact, particularly if there was prior menstrual disturbance. It is crucial to be able to counsel athletes on the effect of age upon reproductive outcomes, the impact of their training on reproductive health, and the implications of fertility treatments, including the impact upon training and performance, and whether the medications involved comply with anti-doping regulations. Elite-level exercise can have a negative impact on menstrual function, however the impact on fertility is less clear. Restoring energy balance may re-establish menstruation and enhance fertility, but some individuals may need fertility treatment. Athletes wishing to wait until after retirement to conceive may encounter age-related reproductive decline, hence some may wish to consider oocyte/embryo preservation. Giving athletes evidence-based information regarding their reproductive health remains challenging due to their underrepresentation in exercise-related research.

Gonadotropin storage and trafficking.

Gonadotropins are synthesized in gonadotropes of the anterior pituitary, and they orchestrate reproductive function in vertebrates. LH and FSH share a common α-subunit that is non-covalently associated with a hormone - and receptor-specific β-subunit. Despite synthesized in the same cell, i.e., gonadotrope the trafficking and secretion patterns of LH and FSH are distinct. FSH is mostly constitutively secreted, whereas LH is stored in dense core granules and is released as a bolus via the regulated pathway in response to gonadotropin-releasing hormone. To comparatively review the storage and secretion patterns of gonadotropins in vertebrates. Gonadotropin storage patterns are comparatively analyzed in vertebrates starting from primitive fish all the way up to higher mammals. The published work on gonadotropin trafficking/secretion patterns using in vitro and in vivo approaches is critically discussed. Primitive fish (lampreys and hagfish) express a single gonadotropic hormone. From these early vertebrates, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) have evolved as two distinct hormones. In several species, including teleost fish, monohormonal gonadotropes are present that express either LH or FSH. In higher vertebrates, the majority of the gonadotropes (>90%) are bihormonal and contain both LH and FSH. Both in vitro (cell transfection and expression) and in vivo (transgenic mouse) studies identified that the LHβ caroboxy terminus heptapeptide is a gonadotrope-specific regulated pathway sorting determinant. When FSH is genetically rerouted from the constitutive trafficking mode and is engineered (LHβ heptapeptide fused to FSHβ subunit) to exit via the regulated pathway in gonadotropes of transgenic mice, it resulted in enhanced ovulations due to suppression of atresia and apoptosis and increased pro-survival pathways in ovaries. However, rerouted FSH expressing male mice did not demonstrate any gain of function phenotypes. Understanding the basic molecular mechanisms of gonadotropin storage/trafficking and secretion may eventually lead to clinical benefits of enhancing female reproductive function and reproductive lifespan.

Dynamic microRNA expression profiles in goat ovarian tissues before and after pregnancy.

This study performed transcriptome sequencing of ovarian tissues from JG goats at three key reproductive stages-non-pregnant (8 months old, M8), pregnant (10 months old, M10), and postpartum (12 months old, M12). A total of 93 differentially expressed (DE) miRNAs were identified across all libraries, with the M8 vs. M10 group having the largest number (34 upregulated and 47 downregulated; |log₂ fold change| > 1, FDR < 0.05). These stage-specific DE miRNAs were clustered into four groups, with their target genes primarily enriched in signaling pathways such as Wnt, JAK-STAT, PI3K-Akt, VEGF, and steroid biosynthesis, which are important factors influencing ovarian cell activity, hormone secretion, angiogenesis, and embryonic development. Real-time quantitative PCR verification showed that the expression patterns of the 9 selected DE miRNAs were consistent with the sequencing data. Additionally, through the joint analysis of DE miRNAs and mRNAs, a co-expression network associated with ovarian reproductive function changes was constructed, ultimately highlighting 11 key miRNAs. Dual-luciferase reporter assays further confirmed the direct targeting relationships between core miR-432-5p and CPT1B, as well as miR-455-3p and PLXNB1. In summary, this study revealed the dynamic changes in ovarian miRNA expression profiles from pre-pregnancy to postpartum and their potential molecular mechanisms, providing theoretical support and key molecular targets for miRNAs in reproductive regulation, with significant implications for improving reproductive efficiency in livestock.

Recent advances in the study of reproductive function in pediatric patients with brain tumors

In recent years, pediatric brain tumors have emerged as one of the most common malignant tumors among children. The site of tumor growth and the selected treatment modalities can potentially have a profound and significant impact on the reproductive function of pediatric patients, which is intimately associated with the physical and psychological health of children during their developmental process. Current research studies have demonstrated that pediatric patients diagnosed with germ cell tumors, craniopharyngiomas, and medulloblastomas commonly present with reproductive dysfunction. Regrettably, in clinical practice, neurosurgeons frequently fail to allocate sufficient attention to this particular aspect. It is of critical and urgent necessity to explore and elucidate the alterations in reproductive function among pediatric patients with brain tumors, and subsequently institute essential protective measures. This article is dedicated to comprehensively reviewing the latest research advancements regarding the relationship between pediatric brain tumors and reproductive function, thereby providing a valuable reference for safeguarding the reproductive function of pediatric patients afflicted with brain tumors.

High temperature induces reproductive dysfunction in male zebrafish via DNA methylation-mediated tssk6 downregulation.

High temperature induces reproductive dysfunction in male zebrafish via DNA methylation-mediated tssk6 downregulation.

Leaky pollination barrier in edaphic vicarious alpine plants

Adaptation to siliceous versus carbonate substrates is thought to be an important driver of speciation in the alpine flora. The role of the pollination system in the formation and maintenance of such species is presently unclear. Here, we chose three species pairs in the genera Gentiana, Primula, and Rhododendron which often occur in geographic proximity or even sympatry to study the existence of pollination barriers in these lineages. Using remote camera and direct observation approaches, scent and color analyses, we tested the hypothesis whether divergent pollinator communities exist that could help to maintain genetic separation of plant populations adapted to different soil types. We found differences in frequency, diurnal activity and to some extent also community composition of flower visitors in edaphic vicarious species pairs. Floral traits like color and scent as well as flower visitor co-distributions indicate that our study species have divergent but overlapping pollination systems. Our results do not suggest a strong reproductive barrier function of the pollination system. While adaptation to different soils still seems to be the main force keeping edaphic vicarious alpine plants genetically separated, pollinators might mediate hybridization in contact areas.

Prolactin Regulates Seasonal Changes in Renal Rheostasis in Djungarian Hamsters.

Seasonal changes in photoperiod regulate multiple physiological systems in vertebrates, including metabolism, reproduction, and immune function. Kidney mass and renal physiology are known to vary annually, but the endocrine and molecular mechanisms underlying these changes are poorly defined. Prolactin (PRL), a photosensitive hormone is implicated in seasonal energy rheostasis, yet its role in programmed regulation of renal physiology is unknown. Using Djungarian hamsters (Phodopus sungorus), we investigated how photoperiod and PRL regulate seasonal changes in kidney mass, morphology, and transcriptome. Ingestive behaviour, kidney histology, and transcriptomic profiles were assessed. We found that long photoperiods and PRL treatment induced renal hypertrophy and convoluted tubule (CT) expansion, whereas exposure to short photoperiods resulted in a reduction in all measurements. Transcriptomic analysis revealed photoperiod- and PRL-responsive gene modules related to mitochondrial metabolism, solute transport, and epithelial remodeling. Among these, Cdh2, encoding N-cadherin, was downregulated by long photoperiods and PRL, and negatively correlated with CT diameter, suggesting a role in epithelial adhesion during tubular expansion. These findings place prolactin as a key hormonal effector for programmed seasonal kidney function and identify Cdh2 as a target to drive renal physiology.

Butyric acid ameliorates PCOS-related reproductive dysfunction through gut-brain-ovary axis signaling and ovarian steroidogenic factor activation

BackgroundButyric acid deficiency is implicated in polycystic ovary syndrome (PCOS), as evidenced by reduced levels in both clinical and preclinical models. Sodium butyrate (NaBu),a butyric acid substitute, has demonstrated therapeutic potential through gut-brain axis modulation, anti-inflammatory effects, and reproductive function protection. This study investigates NaBu’s mechanistic role in PCOS pathophysiology.MethodsPCOS rats received lipo-coated NaBu diet for three weeks. Systemic and tissue analyses included: serum hormone profiling, lipid metabolism assessment, ovarian/colonic histopathology, Short-chain fatty acids (SCFAs) analysis, and proteomics analysis. Primary granulosa cell cultures with lentiviral transfection elucidated molecular mechanisms. Reproductive performance was evaluated longitudinally.ResultsTreatment with NaBu in PCOS rats resulted in reduced food intake, inhibited weight gain, improved abnormal lipid metabolism, restored estrus cycles and ovulation, lower serum levels of testosterone (T), insulin (INS), and luteinizing hormone (LH), and higher levels of estradiol (E2) and progesterone (P4). Additionally, NaBu treatment improved the morphology of polycystic ovaries, elevated colonic levels of G protein-coupled receptor 41 (GPR41), peptide tyrosine-tyrosine (PYY), and butyric acid, and enhanced reproductive performance in PCOS rats. Proteomic analysis and cell experiments suggested that upregulation of Cytochrome P450 1b1 (Cyp1b1) may play a crucial role in regulating E2 metabolism and P4 production, potentially contributing to the pathogenesis of PCOS and ovarian dysfunction.ConclusionThese findings indicate that NaBu may exert its regulatory effects on appetite and hormone levels in the hypothalamus through the gut-brain-ovary axis, modulating the expression of ovarian steroidogenic factors, thereby improving follicular development and granulosa cell function, and enhancing reproductive performance.

Gliocyte Secretomes as a Source of Growth Factors Affecting the Female Reproductive System

In the context of a growing global trend toward delayed motherhood, which is often accompanied by age-related decline in ovarian reserve and impaired reproductive function, research aimed at developing novel strategies for the assisted reproductive technologies is gaining particular significance. One of the promising approaches is the use of cell-based products in particular biologically active compositions that have a neurotrophin-like effect on the female reproductive system. This study investigates the effects of biologically active compositions—including cryoextracts and conditioned media of cells isolated from the spinal ganglia of neonatal piglets—on the functional state of the reproductive system in female rats at a late reproductive age. Specifically, the study focuses on changes in the parameters of the estrous cycle following administration of these compositions. The results revealed a statistically significant prolongation of the estrus phase in treated animals compared to intact controls, indicating potential activation of ovarian function and a favorable modification of reproductive status. These findings suggest that neurotrophic factors contained in the tested biological products may influence the regulation of primordial follicle development and maintenance of the ovarian reserve. This opens new prospects for the development of therapeutic agents aimed at fertility restoration, particularly in women with diminished ovarian reserve or poor response to conventional gonadotropin stimulation protocols in assisted reproductive technology programs.

Polycystic ovary syndrome and excessive body weight impact independently and synergically on fertility treatment outcomes

BackgroundPolycystic ovary syndrome (PCOS) and obesity can both disrupt reproductive function. However, the extent to which obesity contributes to PCOS manifestations is not very clear. This study aimed to disentangle the relative contributions of PCOS and obesity for reproductive dysfunction in women undergoing in vitro fertilization (IVF).MethodsA total of 129 women undergoing IVF treatments were recruited. Women were allocated into four groups according to body mass index (BMI) and PCOS diagnosis: normal-weight controls (n = 33; 21.70 ± 1.85 kg/m²), overweight/obesity controls (n = 28; 28.35 ± 3.05 kg/m²), normal-weight PCOS (n = 31; 21.92 ± 1.95 kg/m²), and overweight/obesity PCOS (n = 37; 31.67 ± 5.03 kg/m²). Circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), glucose and insulin were measured in all groups, while insulin resistance was assessed by the Homeostatic Model (HOMA-IR). Additionally, on the oocyte retrieval day, ∆4-androstenedione, testosterone, progesterone and sex hormone-binding globulin (SHBG), were measured in plasma and follicular fluid (FF). IVF outcomes evaluated included the number of oocytes retrieved, oocyte immaturity, as well as fertilization and blastocyst formation rates. A multivariate analysis was performed to determine the independent effects of PCOS and obesity for reproductive and metabolic parameters.ResultsWomen with PCOS presented significantly higher AMH levels, LH: FSH ratio, and lower FF progesterone levels, confirming these as PCOS-specific signatures regardless of BMI. In contrast, women with overweight/obesity had lower plasma and FF SHBG levels and greater HOMA-IR, independently of PCOS. Furthermore, ∆4-androstenedione and testosterone levels in plasma and FF were significantly higher in women with PCOS and overweight/obesity as compared to normal-weight women with PCOS. Despite the higher oocyte retrieval rates in women with PCOS, no differences in oocyte immaturity, fertilization and blastocyst formation rates were observed.ConclusionsPCOS and obesity independently disrupt female reproductive function suggesting that features associated with each condition may differ. Furthermore, our study shows that obesity exacerbates hyperandrogenism in women with PCOS, highlighting a synergistic detrimental impact on female reproductive function.