Research mechanism of DBP and DEHP in the development of PCOS based on network toxicology and molecular docking.

Abstract

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.