Reproduction & fertility最新文献

Abstract: With rising global temperatures, it is imperative to determine the impact of heat stress on the physiology of food producing animals. Dairy cows are susceptible to uterine diseases that reduce fertility. Immune function is important in the development and progression of disease; however, the effect of heat shock on the innate immune capacity of endometrial epithelial cells remains underexplored. Here, we investigated how heat shock alters the innate immune response and mitochondrial respiration of bovine endometrial epithelial cells. Primary endometrial epithelial cells were collected from postpartum cows and cultured in the presence of lipopolysaccharide under thermoneutral (38.5°C) or heat shock (40.5°C) conditions. Time-course and sequential heat shock experiments were conducted to assess gene expression dynamics of HSPA1A, TLR4, CXCL8, IL6, and IL1B. Cell viability was evaluated by MTT assay, and mitochondrial respiration was analyzed using high-resolution respirometry. Heat shock did not affect cell viability or overall mitochondrial respiration but reduced proton leak-related oxygen consumption. Acute heat shock induced HSPA1A expression but suppressed LPS-stimulated CXCL8 and IL6 expression. Expression of TLR4 increased when cells were recovering from heat shock or following sequential heat shock. Sequential heat shock did not affect the expression of proinflammatory mediators compared to a single heat shock event. In conclusion, acute heat shock of bovine endometrial epithelial cells reduced the innate immune response to LPS without impacting cell viability or mitochondrial function. Altered endometrial immune function may contribute to the increased incidence of uterine diseases in cows under heat stress conditions.

Lay summary: As global temperatures continue to rise, food producing animals face increasing challenges to their fertility and productivity. Uterine disease in dairy cows reduces fertility and impacts milk production. Heat stress is known to disrupt immune function, but less is understood about how elevated temperatures affect the cells that line the uterus that respond to invading pathogens. We examined how acute heat exposure affects the immune response of uterine cells to respond to pathogens and found that heat shock reduces their ability to produce key immune molecules needed to fight bacteria. This suggests that heat stress directly weakens the natural defenses of the uterus and helps us understand why cows are vulnerable to reproductive diseases during hot weather. Understanding these effects can guide better management strategies to protect animal health in a warming climate.

Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) are thought to arise from distinct yet partially overlapping causes, with a substantial number of cases associated with immune system alterations. We hypothesized that a peripheral blood signature integrating natural killer (NK) cell receptor status, monocyte activation, myeloid-derived suppressor cell (MDSC) abundance, and regulatory T cell (TReg) levels would more accurately distinguish each disorder from non-pregnant healthy controls than any single biomarker. We enrolled 194 women and performed deep immunophenotyping of NK cells, monocytes, MDSC, and TReg. Variable selection was performed with the Boruta algorithm, followed by multivariate logistic regression modelling. For RPL, the final model included five biomarkers, achieving an area under the curve of 0.95 and an accuracy of 90.7%. For RIF, the model retained four biomarkers, yielding an area under the curve of 0.85 and an accuracy of 79.5%. Logistic regression was deliberately chosen to prioritize clinical interpretability and facilitate future translation into a point-based diagnostic score.

Abstract: The jaguar faces significant threats to survival from habitat fragmentation/loss and poaching. Conservation efforts include maintaining ex situ populations in zoos, but breeding success remains limited, necessitating the development of assisted reproductive technologies. This study aimed to optimize ovarian synchronization and artificial insemination (AI) protocols for jaguars by evaluating ovarian follicular activity during oral altrenogest treatment and in response to equine chorionic gonadotropin (eCG)/porcine luteinizing hormone (pLH) regimens, and assessing fertility outcomes with laparoscopic AI. In experiment 1, females were fed altrenogest (0.044 or 0.088 mg/kg, n = 2 per dose) daily for 45 days, but neither dose suppressed ovarian activity. In experiment 2, females received 0.088 or 0.176 mg/kg altrenogest (n = 2 per dose) for 45-48 days and then the alternate dose six months later. After a 5-day withdrawal, 600 IU eCG and 5,000 IU pLH (82 h interval) were administered intramuscularly. All eight cycles produced multiple follicles, but ovulation rates were low and no pregnancies occurred. In experiment 3, five females received 0.176 mg/kg altrenogest, followed by a 7-day withdrawal, 600 IU eCG, and 10,000 IU pLH (90-92 h interval). All females achieved multiple ovulations, and one female conceived, delivering a live cub after 103 days - the first jaguar ever produced from AI. In summary, altrenogest and eCG/pLH treatment following species-specific adjustments was effective for ovarian synchronization in the jaguar. The birth of a live cub following AI validates the effectiveness of this hormone regimen and highlights the potential of AI for population management of this imperiled felid.

Abstract: Prepubertal exposure to gonadotoxic chemotherapy, such as cyclophosphamide (CY), poses a significant risk to long-term fertility by depleting ovarian reserve and impairing oocyte quality. Such treatments are commonly administered to young girls with cancer, and when these individuals later seek assisted reproductive technologies (ARTs), concerns arise regarding the developmental competence and cryotolerance of resulting embryos. Using a mouse model, this study evaluated the impact of prepubertal CY exposure (2 successive weekly doses of 75 mg/kg body weight at 2 weeks of age) on the cryosusceptibility of embryos derived via in vitro fertilization (IVF) at their reproductive phase. Oocytes were collected from superovulated females six weeks post-CY treatment and fertilized in vitro, and the resulting cleavage stage embryos were subjected to vitrification-warming. Embryo survival and quality were assessed by blastocyst formation, inner cell mass (ICM) proliferation in vitro, and the expression of key pluripotency markers (Oct4, Sox2, and Nanog). Results showed no significant differences between CY-exposed and control groups in terms of post-warming survival or marker expression. These findings suggest that maternal CY exposure during the prepubertal period does not adversely affect the cryo-resilience of IVF-derived embryos, offering reassurance for childhood cancer survivors seeking ART treatment.

Lay summary: Chemotherapy given during childhood can harm future fertility, especially in girls who have not yet gone through puberty. One common chemotherapy drug, cyclophosphamide (CY), may reduce the number and quality of eggs in the ovaries. Cancer survivors may be more likely to need IVF (in vitro fertilization) or other fertility treatments, given the impact of the treatment on their fertility. In this study, a mouse model was used to understand whether early-life exposure to CY affects the ability of embryos (created through IVF) to survive freezing and thawing, a common part of IVF treatments. The study found that embryos from mice exposed to CY before puberty survived the freezing process just as well as those from unexposed mice. The quality and health of these embryos, measured by their development and important growth markers, were also similar. These findings provide hopeful news for young girls who receive certain types of chemotherapy, who may still have the option to use IVF in the future without increased risk of embryo damage during freezing.

With the gradual emergence of population issues and the increasing incidence of infertility, the role of assisted reproductive technology (ART) is becoming increasingly important. Accurately, objectively, and comprehensively assessing the blastocyst formation rate and predicting delivery outcomes are urgent problems to be solved. This study retrospectively analyzed the clinical data of patients who underwent ART at Renmin Hospital, Hubei University of Medicine, from June 2017 to January 2020. A regression model for the blastocyst formation rate was established through regression analysis. The results showed that late-stage indicators in ART had a significant impact on the blastocyst formation rate, with top-quality embryos having the greatest effect. A discriminant analysis model for delivery outcome was established. It correctly classified 80.4% of the original grouped cases and 79.6% of the cross-validated grouped cases. the area under the receiver operating characteristic curve (AUROC) was 0.887, indicating that the discriminant model has relatively high predictive diagnostic value. Analysis revealed that blood hCG(human chorionic gonadotropin) results play a crucial role in discriminant analysis model. Additionally, the number of top-quality embryos and the blastocyst formation rate also have a significant impact on the accurate prediction of delivery outcomes. Through analyzing the regression model, we propose exploring early blood markers that can predict the blastocyst formation rate. Simultaneously, a new discriminant model that can directly predict the final delivery outcomes was established.

Cancer can leave young men worried about whether they can ever become fathers. We asked 365 male patients in Shanxi what shaped these worries. Older, less-educated men with advanced or certain cancer types felt more fear, while those who already had children, earned more money or still wanted children felt calmer. Good social support, better coping skills and strong self-belief lowered fear, whereas avoidance or giving up made it worse. Doctors should offer emotional, social and practical help to ease these concerns.

Abstract: Low oocyte retrieval (LOR), defined as oocytes retrieved from <50% of mature follicles, significantly impacts IVF success, especially in patients with diminished ovarian reserve (DOR). Predictive models tailored for this population are limited. This retrospective cohort study developed a predictive nomogram for LOR risk in first-cycle IVF/ICSI patients with DOR. The data from 2,594 eligible patients were analyzed. LOR was defined as oocyte retrieval rate <50% (oocytes/follicles ≥14 mm on trigger day). Least absolute shrinkage and selection operator (LASSO) regression identified predictors from clinical/endocrine parameters. A multivariate logistic model was built, visualized as a nomogram, and internally validated (bootstrap resampling). Performance was assessed via AUC, calibration, and decision curve analysis. Eight independent predictors were identified: age, basal FSH, AFC, AMH, LH on hCG day, progesterone (P) on hCG day, number of large follicles (≥14 mm) on hCG day, and trigger-to-retrieval time (TR-OPU). The model demonstrated moderate yet acceptable discrimination (AUC = 0.721, 95% CI: 0.678-0.772) and calibration. TR-OPU was significantly shorter in the LOR group (34.85 vs 35.05 h, P < 0.001). DCA confirmed clinical utility. This study establishes a clinical-endocrine nomogram predicting LOR risk in first-cycle DOR patients. Incorporating key factors, such as TR-OPU, ovarian reserve markers (AMH, AFC, and bFSH), and trigger-day hormones, it may help stratify risk but requires external validation before clinical application.

Lay summary: Women with naturally lower egg reserves often face extra challenges with IVF. A common problem is retrieving fewer eggs than expected during the procedure ('low oocyte retrieval' or LOR), which significantly lowers the chance of pregnancy. Doctors lack good tools to predict who is most at risk. Our study analyzed data from 2,594 women with low egg reserves undergoing their first IVF cycle. We created a simple prediction chart that combines key information easily available to doctors: the woman's age, standard hormone blood tests (AMH and FSH), an ultrasound count of egg sacs (follicles), hormone levels on the day of the final IVF trigger shot, and critically - the exact number of hours between the trigger and the egg collection surgery. This chart accurately estimates an individual woman's risk of LOR. Knowing this risk beforehand helps doctors personalize treatment timing and medication, aiming to collect more eggs and improve the chances of a successful pregnancy, while helping patients avoid unnecessary emotional and financial strain.

Abstract: Seasonal reproduction is common among wild mammals, but male fertility traits are often understudied. The rock hyrax (Procavia capensis) is a seasonal breeder with a narrow reproductive window, yet its semen characteristics and seasonal variation remain poorly understood. Our objectives were to develop and validate an electroejaculation protocol for semen collection, and to enable, for the first time, in vivo assessments of sperm morphology, ultrastructure, morphometry, and seasonal variation in semen quality in both captive and wild populations. A total of 70 semen collection attempts were conducted: 17 in captive males at approximately monthly intervals over 1 year and 53 in wild males just before peak mating season and again 2-4 weeks later, across 3 consecutive years (2021-2023). Electroejaculation was well tolerated and effective, particularly around the mating season, eliciting consistent responses and yielding sperm-containing ejaculates in 88.7% of wild procedures. Sperm morphometry revealed a mean total length of ∼56 µm, with ultrastructural features resembling other eutherian mammals. Seasonal analysis demonstrated significantly higher sperm concentration, motility, and normal morphology during peak mating season compared to later samples. Post-peak samples showed increased structural abnormalities, including midpiece and principal piece defects, and signs of disrupted spermatogenesis and epididymal maturation. Cytology and high-resolution scanning electron microscopy confirmed these findings, revealing compromised sperm integrity and elevated round cell counts outside the breeding peak. This study establishes the first in vivo semen collection protocol and comprehensive semen evaluation in the rock hyrax, revealing seasonal variation in male fertility and enabling repeatable, non-lethal reproductive monitoring.

Lay summary: Male fertility traits are poorly characterized in most wild mammals. The rock hyrax (also known as rock rabbit) is a seasonal breeder with a short mating period each year, but little was known about its male reproductive physiology because semen studies relied on post-mortem material. We established a non-lethal protocol for semen collection in rock hyraxes and applied it both in captivity and under natural desert conditions. This enabled detailed analyses of sperm's shape (morphology), architecture (ultrastructure), and dimensions (morphometry), and seasonal semen changes. We found that sperm concentration, motility, and normal morphology were highest during peak breeding season but declined sharply only a few weeks later, accompanied by structural abnormalities and signs of disrupted spermatogenesis. Our study reveals sharp seasonal shifts in male fertility and demonstrates a safe, repeatable method for studying reproduction in wild mammals, with potential applications in conservation and comparative studies among seasonal species.