Reproductive Sciences最新文献

Polycystic Ovarian Syndrome (PCOS) is a complex endocrine disorder whose pathophysiology extends beyond classical mechanisms of insulin resistance and hyperandrogenism. This review critically synthesizes recent advances from the past seven years that challenge conventional views and highlight emerging concepts. Key controversies such as the differing metabolic and reproductive phenotypes of lean versus obese PCOS, the causal versus associative role of gut microbiota dysbiosis, and the bidirectional link between psychological disorders and endocrine imbalance are examined in light of current evidence. We integrate insights from molecular, metabolic, and neuroendocrine research to illustrate how these interrelated mechanisms influence ovulatory function, oocyte competence, and fertility outcomes. Emerging therapeutic directions, including GLP-1 receptor agonists, insulin sensitizers, and neurobehavioral interventions, are discussed with attention to safety, reproductive implications, and long-term efficacy. Overall, this review advances a framework that connects metabolic, reproductive, and psychological dimensions of PCOS, emphasizing the need for individualized, mechanism-based management strategies.

Background: Adenylate cyclase 4 (ADCY4), a member of the adenylate cyclase family, is an enzyme responsible for catalyzing the synthesis of the secondary messenger cyclic adenosine monophosphate (cAMP). Emerging evidence suggests a potential link between ADCY4 expression and the prognosis as well as biological behaviors of specific malignancies. Nevertheless, a systematic investigation into the role of ADCY4 in pan-cancer prognosis and its regulatory influence on the tumor microenvironment remains insufficient.

Methods: This study employed the HPA and GEPIA 2.0 databases to access ADCY4 expression across various human cancers. Utilizing R programming, we analyzed the relationship between ADCY4 expression and clinical characteristics, immune regulatory genes, immune checkpoint molecules, tumor microenvironment (TME) composition, tumor mutational burden (TMB), microsatellite instability (MSI) and drug sensitivity. DNA methylation levels of ADCY4 in uterine corpus endometrial carcinoma (UCEC) tissues were quantified using MethylTarget assay. Furthermore, in vitro experiments were conducted to validate ADCY4 expression patterns and to investigate its functional impact on UCEC cell proliferation and migratory capacity.

Results: Analysis of TCGA datasets revealed a widespread downregulation of ADCY4 expression in multiple cancer types compared to corresponding normal tissues. ADCY4 expression levels demonstrated significant association with patient's prognosis, the expression of immune regulatory genes and checkpoints, and the degree of immune cell infiltration. Enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), indicated that ADCY4-related genes are predominantly involved in the cAMP signaling pathway. In UCEC, high ADCY4 expression was significantly associated with improved overall survival (OS) and disease specific survival (DSS). ADCY4 was confirmed to be downregulated in both UCEC tissues and cell lines. The MethylTarget assay indicated hypermethylation of ADCY4 in UCEC tissues relative to normal controls. Functional assays demonstrated that modulating ADCY4 expression significantly influenced cell proliferation and migration.

Conclusions: Our collective findings suggest that ADCY4 holds promise as a potential prognostic biomarker and a novel target for cancer immunotherapy.

The pathogenesis and progression of endometriosis may involve a complex combination of multiple factors, including chronic inflammation and oxidative stress. Hormonal therapy, the current standard for pharmacotherapy in endometriosis, causes various issues, such as restricting pregnancy during treatment and a high risk of recurrence after treatment discontinuation. This review investigates the use of lactoferrin (LF), a natural iron-binding glycoprotein, and outlines its mechanism of action, its potential as a non-hormonal therapeutic strategy, prospects for clinical application, and associated therapeutic issues. LF exerts anti-inflammatory, iron-chelating, antioxidant effects, and antiproliferative effects by suppressing signaling pathways and exhibits antifibrotic, antiangiogenic, and antibacterial properties. These are thought to be important physiological factors in endometriosis progression, for which LF exhibits a promising therapeutic candidate that could theoretically replace or complement hormone therapy. Observational studies have reported variations in serum and peritoneal fluid concentrations of LF and anti-LF antibodies in patients with endometriosis depending on the endometriosis stage, depicting LF as a potential therapeutic target. Furthermore, an in vitro study demonstrated that LF selectively induced cell cycle arrest in endometriotic stromal cells without affecting that of eutopic endometrial cells. Compared with other non-hormonal therapies, LF has an extremely lower risk of teratogenicity and fetal toxicity and could improve reproductive outcomes and perinatal prognosis, indicating its potential for continuous administration throughout various life stages. Further studies are needed to determine optimal administration routes and dosages for clinical applications.