Reproductive Biology and Endocrinology最新文献

Background: Endometriosis is a chronic gynecological disorder affecting approximately 10% of women of reproductive age. It commonly presents with pelvic pain, dysmenorrhea, and infertility, imposing substantial physical, psychological, and social burdens. Current therapeutic options, such as surgical intervention and hormonal suppression, are constrained by adverse effects and high recurrence rates. Growing evidence implicates immune dysregulation, particularly of macrophages, in the pathophysiology of endometriosis.

Main body: This narrative review synthesizes foundational and clinical research on macrophages in endometriosis and integrates emerging evidence from single-cell RNA sequencing and spatial transcriptomics to refine current models of macrophage heterogeneity, ontogeny, and therapeutic opportunities. In endometriosis, macrophages adopt heterogeneous, context-dependent states rather than a simple binary pattern. Lesions contain macrophage populations that, through cytokines, chemokines, and growth factors, are implicated in chronic inflammation, impaired clearance of cellular debris, angiogenesis, neuroimmune interactions, extracellular-matrix remodeling, and fibrosis. These immune-mediated mechanisms support lesion survival and are thought to exacerbate symptoms. Recent studies have highlighted several therapeutic strategies aimed at modulating macrophage behavior, including the inhibition of their recruitment to ectopic sites, reprogramming of their functional phenotypes from pro-inflammatory to pro-resolving states, and targeting macrophage-related signaling pathways and immune checkpoints. These approaches are currently under preclinical and clinical investigation and hold promise for reducing disease recurrence and minimizing systemic side effects.

Conclusion: Macrophages are emerging as central players in the initiation and progression of endometriosis through their contributions to inflammation, lesion maintenance, and fibrogenesis. Targeting macrophage-mediated pathways offers a novel and potentially effective direction for immunomodulatory therapies. A deeper understanding of macrophage plasticity and function within the endometriotic milieu may pave the way for the development of more precise and durable treatment strategies to improve clinical outcomes.

Objective: In hormone replacement therapy (HRT) cycles of frozen embryo transfer (FET), progesterone-induced endometrial transformation is critical to clinical outcomes. This study aimed to evaluate the interactive impact of the extent of progesterone exposure and the timing of embryo transfer on live birth outcomes.

Methods: This study retrospectively reviewed 3,381 infertile individuals from June 2013 to June 2024. Participants were stratified into four categories based on the number of days of progesterone exposure (P) and embryo developmental stage at transfer (D): P3-D3 group, P3-D4 group, P4-D3 group, and P4-D4 group.

Results: Analysis showed comparable baseline characteristics among all groups, with no significant variation. When progesterone exposure duration was synchronized with embryo developmental day, the P4-D4 group exhibited significantly higher live birth rate (47.58% vs 30.41%), clinical pregnancy rate (58.89% vs 44.33%), and implantation rate (41.17% vs 25.07%) in contrast to the P3-D3 cohort (P < 0.001), along with a significantly lower miscarriage rate (17.2% vs 26.7%, P = 0.025). When progesterone exposure duration was held constant, D4 embryo transfer significantly improved live birth rate over D3 embryo transfer (P3-D4 group vs P3-D3 group: 44.72% vs 30.41%, P = 0.005; P4-D4 group vs P4-D3 group: 47.58% vs 30.80%, P < 0.001). When embryo developmental stage at transfer was fixed, outcomes related to pregnancy showed no variation between the three-day and four-day exposure schedules. progesterone exposure (P > 0.05). To systematically examine and identify the independent clinical factors that significantly influence live birth outcomes in a target population, a logistic regression approach was employed to provide a comprehensive understanding of the underlying relationships. Consistent results were observed.

Conclusion: Frozen embryo transfer cycles prepared with hormone replacement demonstrate higher live birth rates when embryos are transferred on day 4 rather than day 3, regardless of whether progesterone exposure is 3 or 4 days. When embryo developmental stage is fixed (D3 or D4), varying the duration of progesterone exposure (3 vs 4 days) does not significantly influence clinical or perinatal outcomes.

Background: Pelvic congestion syndrome(PCS) is a complex condition, with ongoing controversies regarding its diagnosis, treatment, and long-term effects, especially concerning reproductive health. Endovenous embolization performed for PCS may alter pelvic hemodynamics and ovarian perfusion, which may change ovarian reserve and menstrual cycle characteristics. This study aimed to investigate the efficacy and impact of endovenous embolization on ovarian reserve and menstrual cycle parameters in patients with PCS.

Methods: This retrospective, single-centre study analysed data from 81 patients diagnosed with PCS who underwent endovenous embolization. Symptom-specific Visual Analogue Scale(VAS) scores, serum anti-Müllerian hormone(AMH), follicle-stimulating hormone(FSH), luteinizing hormone(LH), estradiol(E2), prolactin levels, and menstrual cycle characteristics were evaluated before and 6 and 12 months after the procedure. The primary outcome of this study was improvement in symptoms. Secondary outcomes included changes in serum hormone levels and menstrual cycle characteristics. We categorized our study population into four age groups(< 30, 30-34, 35-39, and 40-44 years) to minimize the impact of age as a confounding variable. These groups were designated as G1, G2, G3, and G4, respectively.

Results: A statistically significant decrease was observed in VAS scores related to chronic pelvic pain(CPP), dyspareunia, and dysmenorrhea. A statistically significant decrease in serum AMH levels was observed 6 and 12 months after endovenous embolization. We observed a decline in AMH levels in G1, G2, G3, and G4(9.75±6.67%, 9.48±4.38%, 12.49±12.11%, and 13.79±11.46%, respectively). No significant changes were found in serum FSH, LH, E2, and prolactin levels. Additionally, a statistically significant decrease in menstrual cycle duration was detected after the procedure.

Conclusions: Our study demonstrated that endovenous embolization appears to be an effective treatment modality for symptom relief. The effect of endovenous embolization on ovarian reserve was generally consistent with physiological changes associated with age, but changes in patients under the age of 30 should not be overlooked. Larger, prospective, multi-centre studies are warranted to validate these findings and explore the long-term effects of endovenous embolization regarding reproductive health.

Trial registration: Not applicable.

Background: While much research is available on the implications of environmental and occupational exposures to chemicals on infertility and sperm quality, less is known about the impact of psychosocial work exposures on male reproductive health, including sperm quality. Therefore, this scoping review maps evidence of the psychosocial work factors and their effects on male fertility, including sperm quality.

Methods: Searches were conducted in JSTOR, Central, PubMed, and Web of Science, with additional searches carried out in Google and Google Scholar. The study included only peer-reviewed articles published in the English language, conducted among male working population between January 1990 and January 2024. Two authors independently extracted data from eligible full-text records, which the other two authors reviewed the extracted data.

Results: The search conducted in the selected databases produced 1,322 records, and through a rigorous screening process, 18 full-text peer reviewed articles were included in this review. The findings about the influence of shift work, long working hours, and job strain on male fertility and sperm quality remain inconclusive. Unfortunately, job stress and cognitive weariness reduce male fertility by lowering sperm quality. Fortunately, social support at work is found to buffer the effect of high job demands on sperm quality. Moreover, workers who smoke tobacco, have poor sleep quality, and have history of depression and diabetes are more likely to suffer infertility and have poor sperm quality.

Conclusion: Workplace interventions are needed to match high job demands with adequate job resources such as social support, job control, adequate breaks and rest periods, and to encourage healthy lifestyles for improved reproductive health outcomes among male workers. More quality studies are needed to explore the influence of psychosocial working conditions on sperm quality.

Background: Testicular microlithiasis (TM) is a pathological condition characterized by diffuse calcifications within the seminiferous tubules. Its clinical significance remains controversial. While some studies regard TM a benign imaging finding, others suggest potential associations with impaired fertility and an increased risk of testicular malignancy.

Objective: This study aims to systematically review the existing evidence regarding the relationship between TM and male fertility, incorporating both imaging and physiological perspectives.

Methods: A systematic review was conducted in accordance with PRISMA guidelines. We searched the PubMed, Embase, and CNKI databases from 2003 to 2025 using the keywords "testicular microlithiasis" in combination with "fertility," "spermatogenesis," and "semen analysis." The inclusion criteria comprised clinical studies evaluating TM in the context of male fertility, including imaging techniques, physiological mechanisms, case-control studies, cohort studies, cross-sectional studies, and narrative reviews. Conference abstracts and animal studies were excluded from the review. After rigorous screening, 66 high-quality studies were included for synthesis and analysis.

Results: The prevalence of TM was significantly higher in infertile men (5.54%) compared to the fertile population (1.47%), reinforcing the potential link between TM and male infertility. Bilateral TM was strongly associated with reduced testicular volume, lower sperm retrieval rates, and abnormal semen parameters, indicating a more pronounced detrimental effect on reproductive function. Imaging and physiological data suggest that scrotal ultrasonography, used as the primary diagnostic tool, frequently reveals an elevated testicular resistive index (RI) in patients with TM. Concurrent findings include damage to the seminiferous tubules, aberrant expression of fertility-related genes such as KITLG and BMP7, and dysregulation of the testicular microenvironment, which may underlie impaired spermatogenesis. Additionally, in high-risk populations, TM has been linked to an increased risk of testicular germ cell tumors.

Conclusions: Individuals with bilateral TM and testicular atrophy should be classified as high-risk and closely monitored through routine ultrasound evaluations. Assisted reproductive technologies, such as microdissection testicular sperm extraction (micro-TESE), may be necessary to optimize fertility outcomes. Future research should prioritize large-scale prospective cohort studies and interdisciplinary approaches to elucidate the molecular mechanisms underlying TM and to advance personalized treatment strategies.

The placenta plays a crucial role in maintaining pregnancy stability, regulating fetal growth, and facilitating maternal-fetal exchange. Its proper development relies on placental vasculogenesis and angiogenesis, along with adaptive remodeling of the maternal uterine vasculature. However, the mechanisms underlying placental development and the successful establishment of the maternal-fetal interface remain incompletely understood. As the third gaseous signaling molecule identified after nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H₂S) has been demonstrated to regulate vascular adaptation during pregnancy by promoting angiogenesis and neovascularization. Dysregulated H₂S biosynthesis has been implicated in pregnancy complications, including preeclampsia (PE), fetal growth restriction (FGR), and preterm birth (PTB), underscoring its potential as a therapeutic target. Recent studies have revealed that H₂S regulates placental function via multiple signaling pathways, including activating adenosine triphosphate (ATP)-sensitive K⁺ (K_ATP) channels, large-conductance calcium-activated potassium channels (BK_Ca channels), endothelial nitric oxide synthase (eNOS) signaling, and mitochondrial dynamics. Notably, H₂S-mediated persulfidation of mitochondrial Rho GTPase 2 (Miro2) has been shown to maintain trophoblast invasiveness and promote placental vascular homeostasis. Additionally, exogenous H₂S donors (e.g., GYY4137 and NaHS) have demonstrated therapeutic potential in experimental models, effectively reversing PE-like pathologies, improving placental perfusion, and restoring trophoblast function. Research further indicates that BK_Ca channels play a key role in H₂S-mediated vasodilation by modulating intracellular Ca²⁺ flux, which influences placental vascular tone and perfusion, reinforcing the importance of H₂S in maternal-fetal circulation regulation. This review provides a comprehensive summary of H₂S biosynthesis and metabolism and its regulatory role in early placental development. Notably, elevated estrogen levels during pregnancy have been identified as key regulators of H₂S production, and we discuss the molecular mechanisms by which estrogen modulates H₂S synthesis. Furthermore, we discuss the vascular-protective and anti-inflammatory properties of H₂S donors and dual-donor strategies. As research continues to reveal H₂S-mediated mechanisms in placental function and pregnancy disorders, optimizing the pharmacological application and clinical translation of H₂S donors and combination therapies will be a key research focus. Advancing H₂S metabolic regulation, signaling pathways, and targeted delivery systems may drive the development of novel diagnostic tools and therapeutic strategies for pregnancy complications.

Male infertility, a significant global public health challenge, arises from multifactorial interactions involving genetic, metabolic, and psychological factors. While psychological stress (depression/anxiety/stress, DAS) is increasingly linked to impaired sperm quality, its molecular mechanisms remain unclear. This cross-sectional study investigates mitochondrial metabolic reprogramming via the pyruvate dehydrogenase kinase (PDK)-pyruvate dehydrogenase complex (PDC) axis under psychological stress, exploring multidimensional impacts on semen quality.Approved by three tertiary hospitals in Central China, 557 participants were categorized into DAS and non-DAS groups based on DASS-21 scores, with clinical histories and semen samples collected. Targeted metabolomics (ATP/pyruvate/lactate), lipidomics (free fatty acids), and RT-qPCR (PDK1-4, PDH mRNA) were performed. Results revealed significantly reduced sperm motility in the DAS group (p < 0.01). Mechanistically, DAS upregulated PDK2/PDK4 expression and suppressed PDH expression, driving metabolic reprogramming and mitochondrial dysfunction. This study provides the first evidence that psychological stress impairs sperm motility via PDK-PDC axis dysregulation, offering novel mechanistic insights and potential therapeutic targets for male infertility.

Background: This study investigates whether ovarian structural and hormonal changes over a 13-year period differ between women diagnosed with polycystic ovary syndrome (PCOS) and healthy controls within an unselected population.

Methods: This prospective nested cohort study followed up on a prevalence study conducted in 2009 in an unselected-population. A total of 41 women with PCOS (≥ 35 years-old, diagnosed using the Rotterdam criteria) and 43 age- and body-mass-index-(BMI)-matched healthy controls were included from this cohort. The relationship between ovarian structure and hormonal profiles was tracked over 13 years. Antral follicle count (AFC) and ovarian volume (OV) were assessed by transvaginal/pelvic ultrasonography. Anti-Mullerian hormone (AMH), total testosterone (TT), sex hormone-binding globulin (SHBG), free androgen index (FAI), and dehydroepiandrosterone sulfate (DHEAS) were measured. The cardiometabolic profile of these aging women in same cohort was reported in a recent study.

Results: The mean age (44.1 ± 6.5 vs. 46.4 ± 4.2 years, p = 0.06), BMI (24.7; IQR:21.9-27.8 vs. 25.2; IQR:23.2-28.9, p = 0.16), and proportion of women in postmenopausal stage (75.6% vs. 62.8%, p = 0.24) were comparable between PCOS and control groups. Ovarian volume and AFC were significantly higher in the aging women with PCOS. At 13 years follow-up, PCOS group experienced a greater decline in AFC, AMH, and TT but retained higher levels of AMH, TT, FAI, and DHEAS than controls. An AMH cutoff of 1.17 ng/mL showed moderate diagnostic reliability for diagnosing PCOS in aging women, with an area under curve of 0.71 (95% CI:0.60-0.83).

Conclusions: Aging women with PCOS show greater declines in AFC, OV, AMH, and TT but maintain higher ovarian and hormonal levels than controls. Serum AMH provides moderate diagnostic utility for diagnosing PCOS in aging women.

Infertility affects millions worldwide, and implantation failure remains a critical barrier in assisted reproduction. Endometrial receptivity, a fundamental prerequisite for successful implantation, involves precise regulation of extracellular matrix components, with hyaluronan (HA) being particularly significant due to its structural and signaling roles. This study evaluated the expression of genes involved in HA metabolism and regulation across different phases of the menstrual cycle, particularly emphasizing their role during the window of implantation in normal fertility and repeated in vitro fertilization failures. Analysis of publicly available transcriptomic datasets revealed distinct expression patterns of HA synthases (HAS2, HAS3), HA-degrading enzymes (HYAL2, CEMIP, CEMIP2), and HA receptors (CD44, RHAMM, layilin) in endometrium that dynamically change toward the receptive state. Notably, HAS enzymes and HA receptors were upregulated during the mid-secretory phase, whereas classical HA-degrading enzymes showed complex regulation, suggesting a balance between HA synthesis and degradation necessary for optimal endometrial function. In patients with repeated IVF failure, there was significant downregulation of key HA-related genes (HAS2, HAS3, CEMIP, CD44, versican, syndecans), implicating impaired HA metabolism in implantation failure. The results underscore the role of HA metabolism and HA receptors in establishing a receptive endometrial environment, highlighting HA and its associated pathways as potential therapeutic targets to enhance reproductive success rates. Further research is necessary to unravel the detailed molecular mechanisms of HA-mediated regulation and its translational implications for assisted reproduction technologies.