Apigenin Regulates Bisphenol-A Induced Polycystic Ovarian Syndrome (PCOS) Symptoms In-Vivo Zebrafish.

Abstract

Bisphenol A (BPA) is an environmental pollutant known to induce oxidative stress and reproductive toxicity, symptoms that are commonly associated with Polycystic Ovary Syndrome (PCOS). This study investigates the potential protective effects of Apigenin (AGN), a bioactive flavonoid, against BPA-induced PCOS-like symptoms in adult zebrafish. The research aims to explore the therapeutic potential of natural compounds in mitigating the effects of environmental endocrine disruptors. Zebrafish were exposed to BPA at a concentration of 10 µg/L, a level known to adversely affect aquatic organisms. The non-toxicity and efficacy of AGN were assessed through a dose-response study involving concentrations of 5, 10, 15, and 20 µM. The experimental design was informed by computational molecular dynamics, including docking and simulations targeting the human androgen receptor. The study involved histological staining of ovarian tissues, biochemical assays for antioxidant enzyme activities, high-performance liquid chromatography (HPLC) for BPA accumulation, and gene expression analysis targeting PCOS-susceptible genes. AGN treatment significantly modulated antioxidant defenses in zebrafish, restoring activities of enzymes such as superoxide dismutase (SOD) and catalase (CAT), and reducing lactate dehydrogenase (LDH) levels. Histologically, AGN mitigated follicular damage and prevented excessive collagen deposition and ovarian hypertrophy, with the gonadosomatic index (GSI) approaching control levels. HPLC analysis confirmed lower BPA accumulation in tissues of AGN-treated groups. Additionally, gene expression studies showed downregulation of PCOS-related genes and TNF-α. AGN exerts a protective role against BPA-induced reproductive toxicity and offers potential as a natural intervention for both ecological and reproductive health challenges.