Reproductive Sciences最新文献

Oligoasthenozoospermia (OAT) is a major cause of declining male fertility worldwide, characterized by reduced sperm count and motility. Its pathogenesis involves multiple factors including genetics, hormones, environment, and lifestyle. Due to ethical and practical limitations in human studies, animal models have become essential tools for elucidating OAT mechanisms and evaluating therapeutic strategies. This review aims to systematically organize and evaluate existing OAT animal models, including those established through chemical agents, heavy metals, endocrine disruptors, physical stress, genetic modification, and nutritional imbalance. It summarizes these models based on their mechanistic foundations, phenotypic characteristics, advantages, and limitations. Results indicate that despite significant research advances, existing models remain limited in standardization, depth of mechanism elucidation, and clinical translational value. Therefore, future efforts should focus on developing more comprehensive and clinically relevant animal models to deepen understanding of OAT pathophysiology and advance the development of effective and personalized therapeutic strategies.

Ovarian serous cystadenocarcinoma (OV) is one of the deadliest gynecologic cancers, primarily due to late-stage diagnosis and limited treatment options. Precision oncology seeks to personalize cancer treatment based on individual genetic profiles and tumor characteristics. The solute carrier (SLC) transporter superfamily, consisting of over 400 proteins across 65 families, is vital for numerous cellular functions and presents promising therapeutic targets. This study provides a comprehensive analysis of SLC transporters by integrating mRNA and protein expression from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA). Gene Set Enrichment Analysis (GSEA) was performed to evaluate the involvement of SLC transporters in diverse oncogenic pathways. Significant upregulation of SLC transporters was observed in tumor tissues compared to normal tissues, notably for SLC57A5, SLC16A3, SLC20A2, and SLC34A2. This upregulation was associated with poorer overall survival (OS) and disease-specific survival (DSS). Gene Set Enrichment Analysis (GSEA) indicated that these transporters are significantly involved in crucial oncogenic pathways, including the epithelial-mesenchymal transition (EMT), angiogenesis, and Hedgehog signaling pathways. This study identifies SLC transporters as potential biomarkers and therapeutic targets in OV. By targeting these transporters with small molecule inhibitors, it may be possible to disrupt essential metabolic pathways in cancer cells, thereby enhancing treatment efficacy and improving patient outcomes. This research establishes a foundation for the development of SLC-targeted therapies in precision oncology, aiming to improve survival rates for patients with OV.

The association between adenomyosis and uterine torsion, a rare, serious obstetric condition, remains unclear and has not been systematically investigated. This study aimed to elucidate the incidence, risk factors, and clinical characteristics of uterine torsion in pregnancies complicated by adenomyosis. We conducted a retrospective cohort study of women with adenomyosis undergoing cesarean section at The University of Tokyo Hospital from 2010 to 2023. Adenomyosis was diagnosed via magnetic resonance imaging and/or ultrasonography before and/or during early pregnancy. Uterine torsion was defined as > 45° rotation around the long uterine axis during cesarean section. We compared the clinical characteristics, adenomyotic features and surgical details of women with and without uterine torsion. Among 135 pregnant women with adenomyosis, 70 underwent cesarean section. Within this cesarean delivery cohort, uterine torsion was identified in six (8.6%) women. All torsion cases were asymptomatic and involved focal type adenomyosis; these six cases represented 13.6% (6/44) of the 44 women with focal type adenomyosis in this cesarean cohort. The torsion group required supraumbilical skin incisions (50.0% [3/6] vs. 0% [0/64], P < 0.001) and atypical uterine incisions (83.3% [5/6] vs. 23.4% [15/64], P = 0.006) significantly more often. This study highlights a high incidence (8.6%) of asymptomatic uterine torsion in a cohort of women with adenomyosis undergoing cesarean delivery. These findings suggest that focal adenomyosis may be a key risk factor and generate an important hypothesis that requires further investigation. Surgical planning should consider the possibility of uterine torsion, which may require tailored intraoperative strategies involving non-standard incisions.

Prolonged stress adversely affects male reproductive health, with infertility affecting millions of couples worldwide due to lifestyle and mental health factors. Chronic unpredictable stress (CUS) has been shown to induce testicular dysfunction via blood-testis barrier (BTB) disruption. The BTB, maintained by ectoplasmic specialisations (ES), is regulated by β1-integrin and phosphorylated focal adhesion kinase (FAK)-associated proteins. Still, the impact of prolonged stress on these regulators has not been fully explored. This study investigated CUS-induced testicular damage over extended durations. Sprague-Dawley rats were exposed to CUS for 8, 14, or 18 weeks, with respective controls (n = 6/group). Depressive behaviour was confirmed by increased anhedonia, anxiety-like behaviour, and corticosterone levels, alongside decreased exploratory activity. Sperm count, motility, morphology, and chromatin integrity were significantly reduced, particularly in the 14- and 18-week CUS groups. FSH, LH, and testosterone levels were also decreased in all CUS-exposed groups. Western blot analysis revealed marked reductions in BTB markers, 11β-HSD, and irisin, with increased testicular apoptosis. Disruption of pFAK (Tyr397) signaling destabilized the apical ES, while reduced pFAK (Tyr407) expression and decreased levels of p-Akt, p-mTOR, and phospho-p70S6 kinase loosened tight junctions. Overall, prolonged CUS exerted cumulative adverse effects on male reproductive function, with both the magnitude and duration of stress critically influencing severity. These findings elucidate the mechanism by which chronic stress compromises BTB integrity and impairs spermatogenesis, highlighting the progressive nature of stress-induced reproductive dysfunction.

The study investigated whether asialoglycoprotein receptor 1 (Asgr1) can serve as a biomarker for polycystic ovary syndrome (PCOS). It is known that Asgr1 loss-of-function variants are associated with lower cholesterol levels and reduced cardiovascular disease risk, but its role as a PCOS biomarker was unclear. In this clinical translational study involving 60 women undergoing IVF at the Assisted Reproductive Center of Northwest Women's and Children's Hospital in Xi'an, China (including controls and PCOS patients), Asgr1 levels in granulosa cells were significantly higher in PCOS women compared to controls (1.2 [0.6-1.8] vs. 2.0 [1.3-2.9], p < 0.001). The receiver operating characteristics curve showed Asgr1 had a predictive value of 0.747 (95%CI: 0.623-0.870) for PCOS. Among individuals with a BMI of 18.5-25 treated with a gonadotropin-releasing hormone (GnRH) agonist protocol, Asgr1 levels positively correlated with gonadotropin dosage. While this is the first study to link Asgr1 to PCOS, its sample size was limited, requiring larger cohorts to confirm Asgr1's predictive accuracy for PCOS. The findings provide a potential new biomarker for PCOS diagnosis.

This systematic review and meta analysis was conducted to investigate the reproductive outcomes in the patients with adenomyosis after HIFU treatment, aimed to recommend HIFU treatment for those women with adenomyosis who have reproductive demand. Extensive search was performed through PubMed, EMBASE and Web of Science databases. All available studies that evaluated the reproductive outcomes after HIFU for adenomyosis. Systematic review was performed following PRISMA guidelines. A meta-analysis was performed on data from 15 studies involving 3730 patients with adenomyosis. Pooled results showed that the pregnancy rate (PR) in women who desired to conceive was 54.6%, the live-birth rate (LBR) based on pregnancy was 75.8%, and the possible prognostic factors were non-perfused volume (NPV%) and type of adenomyosis. This review suggests that HIFU was easier to operate, with less adverse events and noninferior to adenomyomectomy. Patients with higher non-perfused volume (NPV%) and focal or internal adenomyosis had more improvement in reproductive outcomes after HIFU treatment. However, the well-designed, prospective, randomized controlled trials (RCT) are needed to compare the reproductive outcomes in those adenomyosis patients after HIFU in the near future.

The extracellular matrix (ECM) critically influences cell behavior, yet its properties in human endometrial lesions (HEL) and human uterine fibromas (HUF) are not well characterized. This study aimed to characterize their ECM and evaluate its impact on cell engraftment and proliferation while optimizing a decellularization protocol. HEL and HUF tissues, collected during laparoscopic surgeries, were decellularized using a novel protocol. Complete cell removal and preserved ECM microstructure were confirmed by histology, DAPI, Masson's trichrome staining and scanning electron microscopy. The decellularized scaffolds were used as a platform for three-dimensional culture of human endometrial-derived mesenchymal stem cells (hEMSCs), with HUF serving as a fibrotic control originated from the same organ system. The biological impact of the ECM was assessed via immunohistochemistry for engraftment marker matrix metalloproteinase-9 and proliferation marker antigen Kiel-67. The in vivo recellularization potential of HEL scaffolds was further evaluated in a rat model, with HEL scaffold group at two timepoints (n = 6/group) and a sham control (n = 3). Results confirmed complete decellularization with maintained ECM integrity in both HEL and HUF. In vitro evaluation indicated that hEMSCs seeded more efficiently onto HEL scaffolds (51.16 ± 28.84) compared to HUF scaffolds (6.16 ± 7.29) (p = 0.012). The in vivo peritoneal implanted HEL scaffolds demonstrated significant time-dependent host cell recruitment and remodeling compared to the sham control. In conclusion, the decellularized HEL scaffold provides a superior ECM platform for cell seeding and engraftment compared to HUF, making it a promising platform for modeling endometriosis in both in vitro and in vivo settings.

E2F family transcription factors are involved in various cancers, yet the role of E2F transcription factor 8 (E2F8) in endometrial cancer (EC) remains elusive. This study explores how E2F8 transcriptionally activates denticleless E3 ubiquitin protein ligase homolog (DTL) to promote EC progression via the MAPK signaling. Bioinformatic analysis of the GEO dataset GSE63678, along with GEPIA2, AnimalTFDB v4, and ChIP-Atlas, identified E2F8 and its potential target DTL in EC. Elevated expression of E2F8 and DTL was confirmed in EC tissues, which correlated with a higher International Federation of Gynecology and Obstetrics stage. Functional assays demonstrated that E2F8 knockdown suppressed EC cell proliferation, migration, invasion, and MAPK pathway activation, while DTL overexpression or PDCD4 knockdown reversed these effects. Knockdown of DTL enhanced PDCD4 ubiquitination. In vivo, silencing of E2F8 inhibited tumor growth in EC xenograft models, whereas DTL upregulation or PDCD4 knockdown restored tumor progression and enhanced MAPK pathway activity and Ki67 expression. In conclusion, E2F8 promotes EC progression by transcriptionally activating DTL and activating the MAPK pathway. These findings provide novel mechanistic insights into EC progression and suggest that the E2F8/DTL/PDCD4/MAPK axis may serve as a potential therapeutic target for EC.