Reproductive Biology and Endocrinology最新文献

Diabetes mellitus (DM), a chronic metabolic disease with a high global prevalence, has increasingly been recognized for its adverse effects on the male reproductive system, particularly spermatogenesis. This review systematically summarizes the multifaceted impacts of diabetes on spermatogenesis, encompassing molecular mechanisms such as oxidative stress, endocrine disruption, dysregulated gene expression, metabolic imbalance, apoptosis, microcirculation impairment, and chronic inflammation, as revealed by recent studies. The intricate effects of these mechanisms on sperm quality, reproductive function, and offspring health are also thoroughly explored. A key innovation of this review lies in integrating recent advances, especially those highlighting the roles of epigenetic modifications, mitochondrial dysfunction, and insulin resistance (IR)-related pathways in spermatogenesis. Furthermore, the review evaluates the potential of personalized interventions, including glycemic control, antioxidant therapies, and lifestyle modifications, providing a scientific foundation for the development of more effective preventive and therapeutic strategies. This comprehensive analysis offers forward-looking guidance for future research and clinical interventions addressing diabetes-associated male infertility.

Background: Polycystic ovary syndrome (PCOS) is widely acknowledged as the prevailing reproductive endocrine disorder accompanied by numerous metabolic dysfunctions. However, there has been a lack of systematic examination regarding the amino acids profile in PCOS. There is a dearth of evidence in regard to the examination of connections between amino acid metabolites found in follicular fluid (FF) and the quality of embryos during in vitro fertilization (IVF).

Objective: Our objective was to assess amino acid signatures associated with PCOS, as well as identify potential amino acid markers for evaluating embryo quality in PCOS.

Methods: The cohort study consisted of 143 women who were undergoing lVF/ICSl. Among these, 79 patients who had been diagnosed with PCOS, while the remaining 64 patients did not have PCOS. The concentrations of 30 amino acids present in FF were accurately determined through the use of high-performance liquid chromatography-tandem mass spectrometry. We use the spearman correlation was used to calculate correlations. Odds ratio (ORs) and 95% CIs between differential metabolites and embryo mass were estimated by the logistic regression.

Results: The concentrations of glutamine (p = 0.025), taurine (p = 0.017), phenylalanine (p = 0.006), arginine (p = 0.002), histidine (p = 0.001), serine (p = 0.001), Tryptophan (p = 0.037), citrulline (p = 0.05), lysine (p = 0.012), sarcosine (p = 0.028) and 1-Methylhistidine (p = 0.006) in the PCOS group were significantly lower than those in the control group. Both PCOS and control groups showed distinct amino acid profiles between quality subgroups: in PCOS, taurine, aspartic acid, and threonine were higher in the top-quality subgroup, while in controls, alanine, glutamic acid, tyrosine, tryptophan, glycine, ornithine, threonine, and methionine were lower in the poor-quality subgroup. Lower amino acid concentrations were associated with a lower probability of high-quality embryos from IVF. We also identified 11 and 3 amino acids that related to embryo quality in the control and PCOS groups respectively.

Conclusion: Our research has the potential to provide valuable insights regarding the involvement of amino acid abnormalities in follicular fluid in the pathophysiology of PCOS. The findings indicated the possibility of variations in amino acid composition, and consequently variations in embryo quality, among normal and PCOS women. Additional research is required in order to substantiate these findings and directly assess the effects on pregnancy and live birth outcomes.

Background: Testosterone plays a pivotal role in male reproductive health and is synthesized primarily by Leydig cells (LCs) in the testes. Alterations in testosterone levels can lead to sexual dysfunction, reduced fertility, and various systemic health issues. FTO, an m⁶A demethylase, has been implicated in the regulation of RNA modification and has significant roles in various biological processes. However, its influence on testosterone secretion in LCs remains unclear.

Objective: This study aims to investigate the role of FTO in regulating testosterone secretion by LCs and to explore the potential impact of hCG treatment in rescuing the effects of FTO inhibition.

Methods: In this study, we assessed the mRNA and protein expression levels of FTO in LCs from 39 male patients diagnosed with obstructive azoospermia. Additionally, FTO knockdown was performed in TM3 cells, followed by analysis of cell proliferation, apoptosis, and testosterone secretion. The effect of hCG on rescuing FTO inhibition-induced changes was also evaluated.

Results: We identified a positive correlation between FTO expression levels and testosterone concentrations in LCs from 39 male patients with obstructive azoospermia. FTO knockdown in TM3 cells significantly reduced testosterone secretion, cell proliferation, and increased apoptosis. Specifically, 48 h post-transfection, the apoptosis rate in shRNA-FTO-transfected TM3 cells was 6.26%, significantly higher than in mock-transfected cells (3.03%, P = 0.013). FTO inhibition also markedly suppressed cell proliferation by 26.2% (P < 0.0001) at 24 h, 34.3% (P = 0.0006) at 48 h, and 21.5% (P = 0.002) at 72 h, as measured by CCK-8 assay. However, the addition of 10 IU hCG significantly rescued the proliferation and reduced the apoptosis rate in the FTO knockdown group. Testosterone secretion in the FTO inhibition group was also significantly lower than in controls at all time points (6, 24, 48, and 72 h), but hCG treatment restored testosterone levels by 26.4% (P = 0.003) at 6 h, 29.4% (P = 0.0026) at 24 h, 18.8% (P = 0.028) at 48 h, and 36.6% (P = 0.0005) at 72 h.

Conclusion: Our study provides new evidence that FTO plays a critical role in regulating testosterone secretion in LCs. Additionally, we demonstrate that hCG treatment can restore testosterone production impaired by FTO inhibition. These findings offer valuable insights into the molecular mechanisms underlying testosterone secretion and may inform therapeutic strategies for male infertility and hypogonadism.

Background: This retrospective cohort study aimed to evaluate the impact of insulin resistance (IR) on clinical outcomes in polycystic ovary syndrome (PCOS) patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment.

Methods: A total of 1,768 PCOS patients undergoing IVF/ICSI cycles at Shenzhen Zhongshan Obstetrics & Gynecology Hospital between October 2010 and November 2024 were stratified into two cohorts: non-IR group (HOMA index < 2.69, n = 867) and IR group (HOMA index ≥ 2.69, n = 901). Baseline characteristics and clinical outcomes were compared between the groups. Linear logistic regression and multivariate logistic regression analysis were conducted to assess the independent impact of IR on fertilization efficiency and pregnancy outcomes.

Results: Patients with IR exhibited significantly higher BMI (25.44 ± 3.55 vs. 21.59 ± 3.20, p < 0.001), longer infertility duration (3.74 ± 2.75 vs. 3.25 ± 2.43, p < 0.001), increased antral follicle counts (26.74 ± 10.74 vs. 25.05 ± 9.79, p < 0.001) and lower basal follicle-stimulating hormone (FSH) level (9.78 ± 3.25 vs. 10.64 ± 3.83, p < 0.001) compared to those without IR. Additionally, the fertilization rate (82.02% vs. 83.86%, p = 0.005) and 2PN rate (81.07% vs. 83.96%, p < 0.001) were significantly lower in PCOS patients with IR. Linear regression indicated that IR had a more pronounced inverse effect on 2PN rate (B: -2.540, p = 0.009) than on fertilization rate (B: -0.664, p = 0.490). Subgroup analysis and interaction analysis demonstrated that IR functioned as an independent risk factor for impaired oocyte fertilization in normal-weight PCOS patients (B: -22.694, p = 0.011). No statistically significant associations between IR status and clinical or live birth pregnancy outcomes were observed in the regression models.

Conclusions: IR adversely affects oocyte fertilization competence and early embryonic development in normal-weight PCOS patients undergoing assisted reproductive technology (ART). These effects may be attributable to IR-induced metabolic dysregulation, which compromises folliculogenic and cytoplasmic maturation processes critical to gamete competence. These findings underscore the importance of addressing metabolic dysfunction in IR-affected PCOS populations to optimize ART outcomes.

Trial registration: This is a retrospective study.

Emerging evidence highlights the decline of testosterone levels among young males, linked to modern lifestyle shifts rather than aging alone. This exploratory cross-sectional study investigates the interplay between modifiable lifestyle factors and testosterone levels in 50 males aged 18-22 years, focusing on underrepresented variables such as exercise type, carbonated beverage intake, and sunlight exposure. Serum testosterone levels were measured via chemiluminescent immunoassay, and lifestyle data were collected through previously validated questionnaires. Multiple regression analyses revealed hypertrophy training (β = 20.3, p < 0.001), sunlight exposure > 60 min (β = 10.3, p = 0.03), and supplement use (β = 20.5, p < 0.001) as positive predictors of testosterone. Conversely, daily carbonated beverage consumption (β=-10.2, p = 0.01), tobacco use (β=-15.6, p < 0.001), and sleep deprivation (β=-18.2, p < 0.001) were significant negative correlates. Diet type influenced outcomes, with non-vegetarians showing higher testosterone (β = 8.7, p = 0.03) compared to vegetarians. Notably, BMI and chronic diseases were nonsignificant in this young cohort. These findings underscore the multifactorial nature of testosterone regulation, emphasizing holistic lifestyle interventions-such as resistance training, reduced ultra-processed food intake, and sleep optimization-as critical for endocrine health in urbanized youth. The study challenges traditional obesity-centric frameworks, advocating for holistic approaches to mitigate endocrine disruption in emerging adulthood.

Obese or overweight patients considering IVF are generally counselled to reduce weight closer to target BMI (i.e., < 30 kg/m²) by interventions entailing dietary change with a structured exercise program. There is little disagreement that supervised weight loss can improve reproductive outcome when successful, although there are refractory cases where weight goals are unmet. Because low-grade chronic inflammation and altered immune function are characteristic of obesity and antagonize implantation, any pre-IVF weight loss facilitated by semaglutide (SG) would be helpful. However, no preclinical data have considered the ovarian implications of SG. Several formulations of SG are now available to assist in chronic weight management, treatment of type-2 diabetes, or both. SG is 31-amino acid lipopeptide with action at the glucagon-like peptide-1 (GLP-1) receptor, which augments insulin secretion while lowering hepatic glucagon output. SG thus enters a multiorgan network where insulin, AMP-activated protein kinase (AMPK), insulin-like growth factor-1 (IGF-1), mammalian target of rapamycin (mTOR), and sirtuin pathways manage ambient nutritional conditions. As GLP-1 directly influences insulin release and curtails satiety, SG adjusts many biochemical cascades where potential interference with oocyte development or embryo/endometrial crosstalk require clarification. Particularly if used outside manufacturer's guidance (i.e., for aesthetic or personal reasons), SG could bring unwelcome challenges to fertility clinics where obesity and dyslipidemia are merely exchanged for the new problems of starvation and sarcopenia. Here we examine known GLP-1 actions where energy balance, ovarian aging, and oocyte competence converge; off label SG use should be avoided until its signaling effects throughout the reproductive axis are more carefully studied.

Background: Age is known to affect the success of assisted reproductive technology (ART) treatment. While significant research efforts have been directed at investigating the effects of aging on oocytes, few studies have examined the effect of aging on the endometrium. We sought to assess whether age negatively impacts peak endometrial thickness achieved in frozen embryo transfer (FET) cycles.

Methods: This was a retrospective cohort study utilizing the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS) database between 2016 and 2020. Young (< 35) and older (≥35yo) non-identified oocyte donor (NOD) recipients were included to assess the impact of age on endometrial thickness; young and older gestational carriers (GCs) served as the respective controls for these two groups. The primary outcome was peak endometrial thickness achieved in an FET cycle; additional outcomes included cycle cancellation rate, clinical pregnancy rate and live birth rate.

Results: We observed a weak association between age and endometrial thickness in both NOD recipient and GC cycles. Though pregnancy rates were slightly lower at endometrial thicknesses < 8 mm, we observed no difference in clinical pregnancy rate with endometrial thicknesses between 8 and 18 mm. We found a significantly higher clinical pregnancy rate in GCs compared to NOD recipients in both the young and older age groups, and noted a decreasing clinical pregnancy rate with age in all groups.

Conclusion: Our data suggest an age-related decline in pregnancy rates in donor oocyte recipients and gestational carrier cycles, in which an endometrial factor would not necessarily be anticipated; this endometrial factor does not appear to be related to endometrial thickness. Therefore, our data support the existence of an endometrial factor that cannot be assessed by measurements of thickness, but nevertheless plays a crucial role in the success of an embryo implantation.

Clinical trial number: Not applicable.