Wang Xiaofei, Li Penghao, Lv Xingyu, Deng Ling, Zhou Yan, Zhang Xuehong
Jinjiang Maternal and Child Health Hospital, Chengdu, Sichuan Province, China.
Jinxin Xinan Women and Children's Hospital, Sichuan Province, China.
Reprod Toxicol. 2024 Dec;130:108723. doi: 10.1016/j.reprotox.2024.108723. Epub 2024 Sep 21.
Bisphenols (BPs) are known endocrine disruptors potentially contributing to the pathogenesis of Polycystic Ovary Syndrome (PCOS). This study aims to elucidate the molecular interactions between BPs and PCOS-related genes and their combined effects on PCOS development. We identified common genes associated with BPs and PCOS using the CTD. Differential expression analysis was performed on three GEO datasets, leading to the identification of differentially expressed genes (DEGs). Protein-Protein Interaction (PPI) network construction, enrichment analysis, single-gene Gene Set Enrichment Analysis (GSEA), and immune cell infiltration analysis were carried out. A nomogram was developed for PCOS risk prediction, and molecular docking studies were performed using AutoDock Vina, with interaction visualizations via PyMOL. We identified 139 common genes between BPs exposure and PCOS, enrichment analysis highlighted pathways related to hormone metabolism, ovarian steroidogenesis, and p53 signaling. Four hub DEGs (PBK, CCNE2, LPCAT2, S100P) were identified, and a nomogram incorporating these genes demonstrated excellent predictive accuracy. GSEA revealed roles in cell adhesion, immune response, and metabolism. ssGSEA analysis showed significant differences in immune cell infiltration between PCOS and control groups, with notable correlations between hub DEGs and immune cells. Molecular docking indicated strong binding affinities between the hub DEGs and BPAF, suggesting potential disruptions induced by BPs. BPs exposure is associated with significant molecular and immunological changes in PCOS, impacting genes involved in hormone regulation, immune response, and metabolic pathways. The strong binding affinities between BPs and key PCOS-related genes reveal their potential role in exacerbating PCOS, providing insights for targeted therapeutic strategies.
双酚类物质（BPs）是已知的内分泌干扰物，可能与多囊卵巢综合征（PCOS）的发病机制有关。本研究旨在阐明双酚类物质与PCOS相关基因之间的分子相互作用及其对PCOS发展的综合影响。我们使用CTD识别了与双酚类物质和PCOS相关的共同基因。对三个GEO数据集进行差异表达分析，从而识别出差异表达基因（DEGs）。进行了蛋白质-蛋白质相互作用（PPI）网络构建、富集分析、单基因基因集富集分析（GSEA）和免疫细胞浸润分析。开发了用于PCOS风险预测的列线图，并使用AutoDock Vina进行分子对接研究，通过PyMOL进行相互作用可视化。我们在双酚类物质暴露与PCOS之间识别出139个共同基因，富集分析突出了与激素代谢、卵巢类固醇生成和p53信号传导相关的途径。识别出四个枢纽DEGs（PBK、CCNE2、LPCAT2、S100P），包含这些基因的列线图显示出优异的预测准确性。GSEA揭示了其在细胞黏附、免疫反应和代谢中的作用。单样本基因集富集分析（ssGSEA）表明PCOS组和对照组之间免疫细胞浸润存在显著差异，枢纽DEGs与免疫细胞之间存在显著相关性。分子对接表明枢纽DEGs与双酚芴（BPAF）之间具有很强的结合亲和力，表明双酚类物质可能会引发潜在干扰。双酚类物质暴露与PCOS中显著的分子和免疫学变化有关，影响参与激素调节、免疫反应和代谢途径的基因。双酚类物质与关键的PCOS相关基因之间的强结合亲和力揭示了它们在加重PCOS方面的潜在作用，为靶向治疗策略提供了思路。
