Search Results (316)

This review aims to discuss how heat stress affects ovarian follicles and oocytes, steroidogenesis, and embryo development in ruminants. The literature shows that quiescent primordial follicles appear to be less susceptible to heat stress, but from the primary follicle stage onwards, they begin to suffer the consequences of heat stress. These adverse effects are exacerbated when the follicles are cultured in vitro. In antral follicles, heat stress reduces granulosa cell viability and proliferation in both in vivo and in vitro models. Oocyte maturation, both nuclear and cytoplasmic, is also compromised, and embryo quality declines under elevated thermal conditions. These effects are linked to intracellular disturbances, including oxidative imbalance, mitochondrial dysfunction, and altered hormonal signaling. The differences between in vivo and in vitro responses reflect the complexity of the biological impact of heat stress and emphasize the protective role of the physiological microenvironment. A better understanding of how heat stress alters the function of ovarian follicles, oocytes, and embryos is crucial. This knowledge is critical to devise effective strategies that mitigate damage, support fertility, and improve outcomes in assisted reproduction for livestock exposed to high environmental temperatures. Full article

Background: Against the backdrop of the large-scale and intensive development of the livestock industry, enhancing the reproductive efficiency of cattle has become a crucial factor in industrial development. Holstein cows, as the most predominant dairy cattle breed globally, are characterized by high milk yield and excellent milk quality. However, their reproductive efficiency is comprehensively influenced by a variety of complex factors, and improving their reproductive performance faces numerous challenges. The ovary, as the core organ of the female reproductive system, plays a decisive role in embryonic development and pregnancy maintenance. It is not only the site where eggs are produced and developed but it also regulates the cow’s estrous cycle, ovulation process, and the establishment and maintenance of pregnancy by secreting various hormones. The normal functioning of the ovary is crucial for the smooth development of the embryo and the successful maintenance of pregnancy. Methods: Currently, traditional sequencing technologies have obvious limitations in deciphering ovarian function and reproductive regulatory mechanisms. To overcome the bottlenecks of traditional sequencing technologies, this study selected Holstein cows as the research subjects. Ovarian samples were collected from one pregnant and one non-pregnant Holstein cow, and single-nucleus transcriptome sequencing technology was used to conduct an in-depth study on the ovarian cells of Holstein cows. Results: By constructing a cell type-specific molecular atlas of the ovaries, nine different cell types were successfully identified. This study compared the proportions of ovarian cell types under different physiological states and found that the proportion of endothelial cells decreased during pregnancy, while the proportions of granulosa cells and luteal cells increased significantly. In terms of functional enrichment analysis, oocytes during both pregnancy and non-pregnancy play roles in the “cell cycle” and “homologous recombination” pathways. However, non-pregnant oocytes are also involved in the “progesterone-mediated oocyte maturation” pathway. Luteal cells during pregnancy mainly function in the “cortisol synthesis and secretion” and “ovarian steroidogenesis” pathways; non-pregnant luteal cells are mainly enriched in pathway processes such as the “AMPK signaling pathway”, “pyrimidine metabolism”, and “nucleotide metabolism”. Cell communication analysis reveals that there are 51 signaling pathways involved in the pregnant ovary, with endothelial cells, granulosa cells, and luteal cells serving as the core communication hubs. In the non-pregnant ovary, there are 48 pathways, and the interaction between endothelial cells and stromal cells is the dominant mode. Conclusions: This study provides new insights into the regulatory mechanisms of reproductive efficiency in Holstein cows. The differences in the proportions of ovarian cell types, functional pathways, and cell communication patterns under different physiological states, especially the increase in the proportions of granulosa cells and luteal cells during pregnancy and the specificity of related functional pathways, indicate that these cells play a crucial role in the reproductive process of cows. These findings also highlight the importance of ovarian cells in pathways such as “cell cycle”, “homologous recombination”, and “progesterone-mediated oocyte maturation”, as well as the cell communication mechanisms in regulating ovarian function and reproductive performance. Full article

Background: Nitric oxide (NO) is an important modulator of ovarian physiology, which contributes to angiogenesis, steroidogenesis, and redox control. The stable metabolites nitrate (NO₃⁻) and nitrite (NO₂⁻) may indicate real-time follicular function during IVF. Methods: In this prospective study, we included 89 women who underwent controlled ovarian stimulation. The Griess test was used to measure NO₂-NO₃ concentrations in follicular fluid collected on the day of oocyte retrieval. Non-parametric and correlation tests were used to investigate the associations between oocyte yield, maturity (MII), fertilization (2PN), embryo development, and hormone levels. Results: Higher NO₂-NO₃ levels were substantially associated with increased total oocyte count, MII oocytes (p = 0.014), and 2PN embryos (p = 0.029). This suggests a strong relationship between NO bioavailability and oocyte competence. NO₂-NO₃ levels showed a positive correlation with estradiol (p < 0.001) and progesterone (p < 0.001), suggesting a possible function in granulosa cell steroidogenesis. Conclusions: Follicular NO metabolites are candidate functional indicators for oocyte quality evaluation and intrafollicular steroidogenic activity. Their predictive value may improve customized IVF treatment, especially in individuals with complicated ovarian phenotypes such as PCOS or decreased ovarian reserve. Full article

Background/Objectives: Adequate vitamin D levels are essential for various physiological functions, including cell growth, immune modulation, metabolic regulation, DNA repair, and overall health span. Despite its proven cost-effectiveness, widespread deficiency persists due to inadequate supplementation and limited sunlight exposure. Methods: This systematic review (SR) examines the relationship between vitamin D and the reduction of cancer risk and mortality, and the mechanisms involved in cancer prevention. This SR followed the PRISMA and PICOS guidelines and synthesized evidence from relevant studies. Results: Beyond genomic actions via calcitriol [1,25(OH)₂D]-receptor interactions, vitamin D exerts cancer-protective effects through mitigating inflammation, autocrine, paracrine, and membrane signaling. The findings reveal a strong inverse relationship between serum 25(OH)D levels and the incidence, metastasis, and mortality of several cancer types, including colon, gastric, rectal, breast, endometrial, bladder, esophageal, gallbladder, ovarian, pancreatic, renal, vulvar cancers, and both Hodgkin’s and non-Hodgkin’s lymphomas. While 25(OH)D levels of around 20 ng/mL suffice for musculoskeletal health, maintaining levels above 40 ng/mL (100 nmol/L: range, 40–80 ng/mL) significantly lowers cancer risks and mortality. Conclusions: While many observational studies support vitamin D’s protective role in incidents and deaths from cancer, some recent mega-RCTs have failed to demonstrate this. The latter is primarily due to critical study design flaws, like recruiting vitamin D sufficient subjects, inadequate dosing, short durations, and biased designs in nutrient supplementation studies. Consequently, conclusions from these cannot be relied upon. Well-designed, adequately powered clinical trials using appropriate methodologies, sufficient vitamin D₃ doses, and extended durations consistently demonstrate that proper supplementation significantly reduces cancer risk and markedly lowers cancer mortality. Full article

Objectives: Our aim is to report an uncommon pituitary activation occurring during the desensitization phase of the gonadotropin-releasing hormone agonist (GnRHa) long protocol, a cornerstone of medically assisted reproduction (MAR) therapy, in a young woman. Results: We present a case of a 33-year-old female patient with secondary infertility, who exhibited a prolonged and asynchronous follicular development during ovarian stimulation using the GnRH antagonist protocol. Therefore, during a repeat attempt, the long GnRH agonist protocol was employed. Surprisingly, rather than achieving suppression with the agonist, ultrasound detected many large follicles in both ovaries, accompanied by extremely elevated estrogen levels, indicating imminent ovarian hyperstimulation syndrome (OHSS). This unusual phenomenon was also observed during a subsequent attempt using the long protocol in another reproductive center. As part of the work-up to identify the underlying etiology, contrast-enhanced magnetic resonance imaging (MRI) of the sella turcica was performed, which revealed an 11 × 13 × 10 mm pituitary macroadenoma without evidence of pathological hormone secretion. The luteinizing hormone-releasing hormone (LHRH) stimulation test showed a normal luteinizing hormone and follicle-stimulating hormone response. Other abnormalities of the hypothalamo–hypophyseal–target-organ axis were not found. Neurosurgical intervention was deemed unnecessary; radiological follow-up of the lesion was recommended. Conclusions: In this case, the clinical presentation was markedly different from the expected suppressive effects of GnRH agonist therapy, with profoundly elevated estrogen levels and clinical signs of imminent OHSS. Notably, hypersensitivity of the adenohypophysis was not demonstrated following a single physiological LHRH stimulation test. However, the presence of a pituitary adenoma identified on MRI raises the possibility that gonadotropin receptor function was altered by the lesion—an effect revealed only after repeated GnRH agonist exposure, resulting in a paradoxical stimulatory response. Full article

Climate change poses an increasing threat to livestock reproduction, with heat stress (HS) known to significantly impair ovarian function. This study aimed to elucidate the impact of HS on ovarian function and circRNA expression profiles in Hu sheep. Twelve ewes were randomly assigned to a control (Con, n = 6) or HS group (n = 6) and exposed to different temperatures for 68 days. Compared with the Con group, HS significantly increased the respiratory rate (108.33 ± 3.72 vs. 63.58 ± 2.42 breaths/min), pulse rate (121.17 ± 3.98 vs. 78.08 ± 3.31 beats/min), and rectal temperature (40.17 ± 0.14 °C vs. 39.02 ± 0.21 °C; p < 0.05). Concurrently, serum antioxidant levels were markedly decreased, including total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px) (p < 0.05). Histological analysis revealed a significant reduction in the numbers of primordial, primary, secondary, and mature follicles, alongside an increase in antral follicles (p < 0.05). TUNEL staining demonstrated enhanced granulosa cell apoptosis (p < 0.05), accompanied by the upregulation of pro-apoptotic genes Bax and Caspase-3 and downregulation of the anti-apoptotic gene Bcl-2, as confirmed by qPCR (p < 0.05). CircRNA sequencing identified 152 differentially expressed circRNAs (120 upregulated, 32 downregulated), and enrichment analyses indicated their involvement in apoptosis, mitophagy, and the FoxO signaling pathway. Collectively, these findings demonstrate that HS impairs ovarian physiology and antioxidant defense, induces follicular damage and cell apoptosis, and alters circRNA expression profiles, providing new insights into the molecular mechanisms underlying HS-induced reproductive dysfunction in Hu sheep. Full article

Per- and polyfluoroalkyl substances (PFASs) comprise a diverse array of synthetic chemicals that resist environmental degradation. They are increasingly recognised as endocrine-disrupting compounds (EDCs). These chemicals, found in non-stick cookware, food packaging, and industrial waste, accumulate in human tissues and fluids, raising substantial concerns regarding their impact on female reproductive health. Epidemiological studies have demonstrated associations between PFAS exposure and reduced fertility; nevertheless, the underlying molecular pathways remain inadequately understood. This narrative review investigates the multifaceted effects of PFASs on ovarian physiology, including its disruption of the hypothalamic–pituitary–ovarian (HPO) axis, alteration of anti-Müllerian hormone (AMH) levels, folliculogenesis, and gonadotropin receptor signalling. Significant attention is directed towards the emerging association between PFASs and polycystic ovarian syndrome (PCOS), wherein PFAS-induced hormonal disruption may exacerbate metabolic issues and elevated androgen levels. Furthermore, we analyse the current data regarding PFAS exposure in women undergoing treatment based on assisted reproductive technologies (ARTs), specifically in vitro fertilisation (IVF), highlighting possible associations with diminished oocyte quality, suboptimal embryo development, and implantation failure. We examine potential epigenetic and transgenerational alterations that may influence women’s reproductive capabilities over time. This study underscores the urgent need for further research and regulatory actions to tackle PFAS-related reproductive toxicity, particularly in vulnerable populations, such as women of reproductive age and those receiving fertility treatments. Full article

Corazonin (Crz) is widely found in insects and crustaceans. In insects, Crz participates in the regulation of various physiological activities, including heartbeat, body color change, molting, and reproduction. However, the physiological effects of Crz in crustaceans remain largely unclear. In this study, the cDNAs encoding Crz and its putative receptor were isolated from the mud crab Scylla paramamosain. Tissue distribution analysis revealed that Sp-Crz was predominantly expressed in neural tissues, while its receptor (Sp-CrzR) was widely expressed in S. paramamosain, with a high expression level in the Y-organ. During ovarian development, Sp-Crz expression in the eyestalk ganglion was upregulated at the early and late vitellogenic stages, whereas its expression level in the cerebral ganglion displayed an initial downregulation at the early stage, followed by a remarkable upregulation at the late vitellogenic stage. The expression level of Sp-CrzR mRNA in the ovary increased significantly at the late vitellogenic stage. However, an opposite expression pattern was observed in the hepatopancreas and Y-organ. The immunohistochemistry result showed that Sp-Crz was distributed in the cells of the lamina ganglionaris, the medulla interna, and the X-organ of the eyestalk ganglion. It was revealed that the level of Sp-Vg in the hepatopancreas was not affected by the addition of Sp-Crz in vitro. However, the expression of Sp-VgR in ovarian explants was significantly induced by 6 h treatment with Sp-Crz at a concentration of 1 nM. In addition, the level of Sp-VgR in the ovary was significantly upregulated by 12 h injection of Sp-Crz. After long-term administration of Sp-Crz, the expression of Sp-VgR in the ovary, the E₂ content in hemolymph, the oocyte diameter, and the gonadosomatic index of S. paramamosain were significantly increased. In summary, these findings collectively indicate that the Sp-Crz signaling system participates in regulating the ovarian development of the mud crab. This study provides a new insight into the biological function of Crz during the ovarian development of the mud crab, which is of great significance for the sustainable development and utilization of mud crab resources. Full article

Assisted reproduction technology (ART) has advanced significantly over the past four decades, leading to improved pregnancy outcomes and a reduction in complications, particularly those associated with multiple pregnancies. These improvements largely stem from advances in understanding embryonic physiology, which has enabled better culture conditions. As a result, embryologists can now efficiently culture embryos to the blastocyst stage and successfully cryopreserve them for future use. However, while incubators aim to replicate the maternal environment of the oviduct and uterus, embryos in vitro are cultured in static conditions, unlike the dynamic, constantly changing environment they experience in vivo. Key factors such as pH, temperature, osmolality, and gas concentrations are crucial for establishing optimal embryo development and implantation potential. Moreover, the vitrification procedure for gametes or embryos can introduce oxidative stress, as well as osmotic shock and cryoprotectant toxicity, which may affect embryo viability and increase the risk of birth defects. Since the first successful ART birth in 1978, over 10 million babies have been conceived through these techniques. Although most of these children are healthy, concerns exist about potential birth defects or changes linked to the handling of gametes and embryos. The preimplantation period is marked by significant epigenetic reprogramming, which can be influenced by ART procedures such as ovarian stimulation, in vitro fertilization, embryo culture, and cryopreservation. However, the long-term health implications for offspring remain uncertain. Epigenetic reprogramming during early embryogenesis is essential for proper embryo development and can be changed by ART-related conditions. These concerns have raised questions about the possible connection between ART and a higher risk of birth defects or other changes in children born through these methods. Therefore, we conducted a scoping review following PRISMA-ScR guidelines to map evidence on ART-related risks, including epigenetic and birth defect outcomes. Full article

Infertility affects 17.5% of couples worldwide, and is notably caused in females by ovarian disorders that impact follicle development and oocyte maturation. Polycystic ovary syndrome (PCOS), affecting 8 to 13% of women of reproductive age, is a leading cause of anovulation and is characterized by arrested antral follicle development before the preovulatory stage. Reproductive issues of PCOS are often exacerbated in overweight or obese women. Obesity, which is increasingly prevalent worldwide, is also associated with anovulation, primarily due to defects in oocyte quality. Oocyte quality and competence depend on the proper activity of granulosa cells (GCs), which surround and support the oocyte. GCs produce key factors, such as 17β-estradiol, which regulate follicle growth and oocyte maturation. They also provide essential metabolic support for oocyte maturation and play a critical role in ovulation and fertilization. This review outlines the physiological role of GCs in follicle growth and maturation and explores recent advancements in understanding GCs’ molecular and physiological dysfunctions that contribute to infertility in PCOS and obesity. Improved knowledge of the endocrine mechanisms underlying follicular abnormalities in these conditions could help to predict oocyte competence and enhance assisted reproduction outcomes. Full article

Proteases play crucial roles in ovarian folliculogenesis, regulating several processes from primordial follicle activation to ovulation and corpus luteum formation. This review synthesizes the current knowledge on the diverse functions of proteases in ovarian physiology and pathology. We discuss the classification and regulation of proteases, highlighting their importance in extracellular matrix remodeling, cell signaling, and apoptosis during ovarian follicular development. We explore the roles of several proteases including matrix metalloproteinases, tissue inhibitors of metalloproteinases, the plasminogen activator system, and cathepsins, and their roles in the critical functions of ovarian biology including follicle dynamics and senescence. Furthermore, we address the involvement of proteases in ovarian pathologies, including cancer, polycystic ovary syndrome, and primary ovarian insufficiency. By integrating recent findings from clinical genomics and animal models, this review provides a comprehensive overview of protease functions in the ovary, emphasizing their potential use for therapeutic interventions in reproductive medicine. Full article

The disposable soma theory posits that organisms allocate limited resources between reproduction, maintenance, and growth, resulting in trade-offs, particularly as they age. In this study, we examined age-related reproductive senescence in Megachile rotundata, a solitary bee and important agricultural pollinator. We hypothesized that, similarly to social bees, aging females would show declines in foraging behavior and reproductive fitness. Contrary to this hypothesis, we found no evidence of reproductive senescence in M. rotundata within the timeframe observed. Instead, older females increased their foraging rate, leading to larger provisions and offspring. We also observed that older bees exhibited improved foraging efficiency, likely due to learning and muscle physiology changes. Furthermore, ovarian development showed no decline with age, indicating that reproductive capacity remains stable throughout the observed timeframe. Our results challenge conventional assumptions about reproductive senescence in solitary bees and suggest that older M. rotundata may contribute to more efficient pollination, with implications for pollinator management. This study provides new insights into the aging process in solitary bees, emphasizing the need for further research into the mechanisms behind age-related behavioral and reproductive changes. Full article

Exosomal microRNAs (ex-miRs), encapsulated in extracellular vesicles (EVs), play a vital role in facilitating paracrine communication among granulosa cells (GCs), cumulus cells (CCs), and the oocyte inside follicular fluid (FF). These small non-coding RNAs are crucial for regulating folliculogenesis, oocyte maturation, and early embryonic development via modulating intracellular signaling networks. Dysregulation o has been associated with reproductive disorders such as polycystic ovarian syndrome (PCOS), diminished ovarian reserve (DOR), and inadequate ovarian response (POR), impacting oocyte quality and fertility outcomes. This narrative review consolidates molecular data from current human and animal studies regarding ex-miR expression patterns, functional targets, and pathway involvement within the context of assisted reproductive technologies (ARTs). A literature-based analysis was undertaken, focusing on signaling pathways, pathogenic processes, and clinical implications. Specifically, ex-miRs—such as miR-21, miR-34c, miR-143-3p, miR-155-5p, miR-339-5p, and miR-424-5p—were identified as regulators of critical pathways including phosphoinositide 3-kinase (PI3K)–AKT, ERK1/2, TGF-β/SMAD, and Rb–E2F1. These ex-miRs regulate apoptosis, glycolysis, mitochondrial function, and cell cycle expansion to influence oocyte competence. Pathological patterns in PCOS and POR are associated with altered ex-miR expression that disrupts metabolic and developmental signaling. Research utilizing animal models confirmed that modifications in EV-associated miRNA influence in vitro maturation (IVM) efficiency and blastocyst quality. Ex-miRs serve as intriguing non-invasive biomarkers and potential therapeutic targets for ARTs. Their mechanical involvement in oocyte and follicular physiology positions them for integration into forthcoming precision-based infertility therapies. For its implementation in reproductive medicine, EV profiling requires standardization and further functional validation in clinical environments. Full article

Background: Assisted reproductive technologies (ARTs) are essential in treating infertility but often face limited success due to low implantation and live birth rates. East Asian traditional medicine (EATM), including acupuncture and herbal medicine (HM), may enhance physiological responses during ART cycles. This study evaluated the effectiveness and safety of EATM in improving clinical pregnancy and live birth outcomes in women undergoing ART. Methods: This review, registered in PROSPERO (CRD42023411712), systematically searched 11 databases up to 31 March 2023. We included randomized controlled trials (RCTs) comparing EATM interventions to control groups. Data extraction and quality assessment were performed independently by two authors. Meta-analysis used the inverse-variance method in Stata 12.0. A total of 37 RCTs involving 10,776 women (aged 29–38) were analyzed. Studies addressed infertility causes including polycystic ovary syndrome, tubal blockage, diminished ovarian reserve, and unexplained infertility. Acupuncture therapies included body, electro-, laser, and auricular acupuncture. Herbal treatments were administered as powders, pills, granules, decoctions, and ointments based on traditional Chinese formulas. Results: EATM interventions were associated with significant improvements in clinical pregnancy and live birth rates. Acupuncture increased clinical pregnancy rates (CPR: RR 1.316, 95% CI 1.171–1.480) and live birth rates (LBR: RR 1.287, 95% CI 1.081–1.533). HM also enhanced CPRs (RR 1.184) and LBRs (RR 1.147). Subgroup analysis showed true acupuncture and HM were more effective than sham or placebo. No significant differences in adverse events were found. Conclusions: EATM, particularly acupuncture and HM, appears to be a safe and effective complementary therapy that can be used to improve ART outcomes. Future research should focus on developing standardized acupuncture and herbal protocols to optimize integration with ART. Full article

Goats are primarily raised in marginal, arid, and semi-arid production systems and exhibit a seasonal reproductive pattern. Extending their reproductive season would enhance food security and improve the economic viability of goat production. Therefore, the objective of this study was to assess the effects of SeVE supplementation during the anestrus season on ovarian activity in anestrous goats subjected to an estrus synchronization protocol. The response variables included estrus induction (EI), ovulatory rate (OR), corpus luteum diameter (CLD), left and right ovary diameters (LOD and ROD), embryo implantation (EMBRYO), and pregnancy rates (PREG). Adult, anestrous, crossbred dairy goats (n = 32) from northern semi-arid Mexico (i.e., Comarca Lagunera, 26° N) were randomly assigned to two homogeneous groups based on age, live weight (LW), and body condition score (BCS): (1) the supplemented group (SeVE; n = 16), received 5 mg selenium plus 350 IU vitamin E, and (2) the control group (CONT; n = 16), received physiological saline. Estrus was induced using a combination of progesterone (P4, 20 mg), equine chorionic gonadotropin (eCG, 400 IU), and exposure to the male effect. While no differences (p > 0.05) were observed between the groups for LW and BCS, the variables EI, OR, EMBRYO, and PREG rates were higher (p < 0.05) in the SeVE group than the CONT group. No differences (p > 0.05) were observed between the groups for CLD, LOD, or ROD. Thus, SeVE-targeted supplementation improved reproductive outcomes without affecting ovarian structure size (i.e., a non-dimensional ovarian SeVE action), suggesting that this precision supplementation strategy certainly enhances reproductive efficiency. This was possibly related to selenium-induced increases in P4 synthesis, and the antioxidant effects on follicular development correlate with improved endometrial development, conceptus survival, embryo growth, and pregnancy maintenance. Such improvements could contribute to the sustainability of marginal production systems in the semi-arid regions of northern Mexico, supporting food security and increasing economic returns for goat producers and their families. Full article