Yi-Fan Kang, Jian-Rong Liu
The Fifth Clinical Medical College of Shanxi Medical University, Shanxi Provincial People's Hospital , Taiyuan, 030001, China.
Shanxi Provincial People's Hospital, Taiyuan, 030001, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 25. doi: 10.1007/s00210-025-04173-0.
Polycystic ovary syndrome (PCOS) constitutes a prevalent endocrine disorder among females, exhibiting a significant incidence rate. The etiology of PCOS predominantly attributes to environmental determinants. Phthalate esters, including dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), have been demonstrated to exert detrimental effects on reproductive function. However, the effects of these plasticizers on female reproductive health have not been clearly investigated. In the present investigation, we employed network toxicological methodologies to delineate the pivotal genes and associated pathways that are implicated in the pathogenesis of PCOS induced by DBP and DEHP. Molecular docking methodologies were employed to ascertain the interaction between the investigational compound and the designated target protein. The present study delineates pivotal targets, namely AKT1, SRC, PIK3R1, EGFR, ESR1, and STAT3, which are instrumental in the mediation of PCOS. The genes predominantly participate in the EGFR pathway, insulin signaling pathway, and oocyte damage, significantly compromising female ovarian functionality. This investigation underscores the integration of network toxicology, molecular docking, and cell experiment methodologies to elucidate the toxicological properties and underlying molecular mechanisms of plasticizers in the context of PCOS. This study provides a prospective therapeutic target to mitigate the harmful effects of plasticizers on female reproductive health.
多囊卵巢综合征(PCOS)是女性中一种常见的内分泌紊乱疾病,发病率较高。PCOS的病因主要归因于环境因素。邻苯二甲酸酯,包括邻苯二甲酸二丁酯(DBP)和邻苯二甲酸二(2-乙基己基)酯(DEHP),已被证明对生殖功能有有害影响。然而,这些增塑剂对女性生殖健康的影响尚未得到明确研究。在本研究中,我们采用网络毒理学方法来描述DBP和DEHP诱导的PCOS发病机制中涉及的关键基因和相关途径。采用分子对接方法来确定受试化合物与指定靶蛋白之间的相互作用。本研究确定了关键靶点,即AKT1、SRC、PIK3R1、EGFR、ESR1和STAT3,它们在PCOS的介导中起作用。这些基因主要参与EGFR途径、胰岛素信号通路和卵母细胞损伤,显著损害女性卵巢功能。本研究强调了网络毒理学、分子对接和细胞实验方法的整合,以阐明增塑剂在PCOS背景下的毒理学特性和潜在分子机制。本研究为减轻增塑剂对女性生殖健康的有害影响提供了一个潜在的治疗靶点。