The effect of phytoestrogens and PAHs on endometriosis and the involvement of gut microbiota, inflammation, and molecular targets

作者：Yanling Chen, Yingtong Jiang, Ziyi Li, Mengyuan Zhu, Amanda Gretta Akimana, Wang Kang, Kun Zhou, Xiaoling Zhang, Xiaoming Ji, Minjian Chen · 发表于：Scientific Reports · 年份：2025 · DOI：10.1038/s41598-025-20042-5 · 被引用次数：3 · 研究领域：Endometriosis Research and Treatment、Reproductive System and Pregnancy、Estrogen and related hormone effects

Endometriosis is a common estrogen-dependent inflammatory disease, yet its complex etiology is not fully understood. Endocrine Disrupting Chemicals (EDCs) exposure disrupts human reproduction, but studies on mixed EDCs and endometriosis risk are Limited. The study Analyzed 2,644 women, assessing 12 phthalates, 8 polycyclic aromatic hydrocarbons, And 6 phytoestrogens in a representative US population. Various statistical models (generalized linear model, partial least squares discriminant analysis, weighted quantile sum, quantile g-computation, restricted cubic spline) were used to explore the link between EDC exposure and endometriosis risk, with mediating effects of lipid metabolism and inflammatory biomarkers examined. Biological mechanisms were identified through an integrated strategy involving target analysis of key chemicals and endometriosis intersections, network establishment, pathway analysis, and target validation. Various statistical models revealed that the gut microbiota metabolite enterolactone (ENL) was negatively associated with endometriosis, while the PAH metabolite 1-Hydroxyphenanthrene (1-OHPHE) was positively associated. Mediation analysis showed that uric acid (UA) and ferritin (Fer) were associated with mediating pathways in the relationships between ENL And decreased risk, And 1-OHPHE and increased risk, respectively. Network and target analysis indicated that ENL affects risk via ESR1, while 1-OHPHE disturbs it through GRB2. ENL can bind to XDH, inhi...