Sudhakaran Gokul, Gopi Sanjay, Priya Snega, Pachaiappan Raman, Soundharrajan Ilavenil, Almutairi Bader O, Arockiaraj Jesu
Centre for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Thandalam, Tamil Nadu, India.
Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu District, Tamil Nadu, 603203, India.
Reprod Sci. 2025 Mar 27. doi: 10.1007/s43032-025-01845-3.
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.
双酚A（BPA）是一种环境污染物，已知会引发氧化应激和生殖毒性，这些症状通常与多囊卵巢综合征（PCOS）有关。本研究调查了生物活性黄酮类化合物芹菜素（AGN）对成年斑马鱼中BPA诱导的PCOS样症状的潜在保护作用。该研究旨在探索天然化合物在减轻环境内分泌干扰物影响方面的治疗潜力。将斑马鱼暴露于浓度为10μg/L的BPA中，该浓度已知会对水生生物产生不利影响。通过涉及5、10、15和20μM浓度的剂量反应研究评估了AGN的无毒和有效性。实验设计参考了计算分子动力学，包括针对人类雄激素受体的对接和模拟。该研究包括卵巢组织的组织学染色、抗氧化酶活性的生化测定、用于BPA积累的高效液相色谱（HPLC）以及针对PCOS易感基因的基因表达分析。AGN处理显著调节了斑马鱼的抗氧化防御，恢复了超氧化物歧化酶（SOD）和过氧化氢酶（CAT）等酶的活性，并降低了乳酸脱氢酶（LDH）水平。在组织学上，AGN减轻了卵泡损伤，防止了过度的胶原蛋白沉积和卵巢肥大，性腺体指数（GSI）接近对照水平。HPLC分析证实AGN处理组组织中的BPA积累较低。此外，基因表达研究显示PCOS相关基因和TNF-α下调。AGN对BPA诱导的生殖毒性发挥保护作用，并为生态和生殖健康挑战提供了作为天然干预措施的潜力。
