Reproductive Sciences最新文献

Primary ovarian insufficiency (POI) is a multifactorial disorder marked by ovarian function cessation before age 40, leading to infertility and systemic complications, including osteoporosis, cardiovascular disease, and neurocognitive impairment. It results from accelerated ovarian reserve depletion, impaired folliculogenesis, and hormonal dysregulation. The majority of cases are idiopathic, with known causes including genetic mutations, autoimmune disorders, infections, and iatrogenic factors. Recent RNA sequencing advances highlight microRNAs (miRNAs) as critical regulators of ovarian processes. Dysregulated miRNAs drive granulosa cell apoptosis, oxidative stress, and follicular atresia, with distinct profiles offering potential as biomarkers for early diagnosis and therapeutic targets. This review synthesizes miRNA-mediated mechanisms in POI, integrating their roles in apoptosis, DNA repair, and folliculogenesis, and evaluates miRNA-based diagnostics and therapies, including exosome-mediated delivery, to improve reproductive and clinical outcomes.

Human papillomavirus (HPV) and Chlamydia trachomatis (CT) co-infection is increasingly recognized not as a mere coincidence, but as a synergistic partnership that accelerates oncogenic progression across multiple tissues. This review synthesizes existing evidence into a "central-peripheral" framework, positioning cervical cancer as the central, mechanistically well-established model of cooperation, while malignancies such as head and neck, ovarian, and breast cancers represent the emerging, though less substantiated, peripheral extensions. This synthesis delineates an emerging paradigm of bidirectional interplay: CT fosters a permissive microenvironment for HPV persistence by impairing host immunity and inducing chronic inflammation, while HPV oncoproteins promote tumorigenesis by disrupting tumor suppressor functions and reprogramming cellular metabolism. These resulting metabolic alterations in the host cell form the basis for the hypothesis of a metabolic co-dependency that may further reinforce CT persistence. The convergence of these pathogens on shared pathways, specifically immune evasion, genomic instability, and metabolic reprogramming, outlines a synergistic network. However, definitive proof of causality, particularly for the bidirectional effects in non-cervical cancers, remains constrained by methodological heterogeneity. Bridging these gaps requires future research to leverage immunocompetent co-infection models and multi-omics approaches. Elucidating the HPV-CT interactome supports a conceptual shift from a single-pathogen to a multi-pathogen oncogenesis model, which is pivotal for developing the next generation of precision prevention and therapy.

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.