Bisphenol A (BPA) is a highly pervasive chemical in consumer products with its ascribed endocrine-disrupting properties. Several studies have shown the cytotoxic, genotoxic, and carcinogenic property of BPA over a multitude of tissues. Although BPA exposure has earlier been implicated in female infertility, the underlying molecular mechanisms explaining the toxicity of BPA in the ovary remains less understood. In the present study, a plausible correlation between redox balance or inflammatory signaling and reproductive fitness upon BPA exposure has been examined in zebrafish (Danio rerio) ovary. Congruent with significant alteration of major antioxidant enzymes (SOD1, SOD2, catalase, GPx1α, GSTα1) at the transcript level, 30 d BPA exposure at environmentally relevant concentrations (1, 10 and 100 μg L^–1) promotes ovarian ROS/RNS synthesis, lipid peroxidation but attenuates catalase activity indicating elevated stress response. BPA promotes a sharp increase in ovarian p38 MAPK, NF-κB phosphorylation (activation), inducible nitric oxide synthase (Nos2a), and pro-inflammatory cytokines (TNF-α and IL-1β) expression, the reliable markers for inflammatory response. Congruent to an increased number of atretic follicles, BPA-exposed zebrafish ovary reveals elevated Bax/Bcl2 ratio, activation of caspase-8, -3 and DNA breakdown suggesting heightened cell death. Importantly, significant alteration in nuclear estrogen receptor (ER) transcripts (esr1, esr2a, and esr2b) and proteins (ERα, ERβ), gonadotropin receptors, and markers associated with steroidogenesis and growth factor gene expression in BPA-exposed ovary correlates well with impaired ovarian functions and maturational response. Collectively, elevated oxidative/nitrosative stress-mediated inflammatory response and altered ER expression can influence ovarian health and reproductive fitness in organisms exposed to BPA environment.

双酚A（BPA）是消费类产品中高度普及的化学物质，具有归因于内分泌干扰的特性。多项研究表明，BPA对多种组织具有细胞毒性，遗传毒性和致癌性。尽管BPA暴露较早地与女性不育症有关，但解释BPA在卵巢中毒性的潜在分子机制仍然鲜为人知。在本研究中，已经在斑马鱼（Danio rerio）卵巢中检查了BPA暴露后氧化还原平衡或炎症信号与生殖适应性之间的合理关联。与转录物水平上的主要抗氧化剂酶（SOD1，SOD2，过氧化氢酶，GPx1α，GSTα1）发生显着变化，在环境相关浓度（1、10和100μgL时）暴露30 d BPA^–1）促进卵巢ROS / RNS合成，脂质过氧化，但减弱过氧化氢酶活性，表明应激反应增强。BPA促进卵巢p38 MAPK，NF-κB磷酸化（激活），诱导型一氧化氮合酶（Nos2a）和促炎性细胞因子（TNF-α和IL-1β）的表达急剧增加，后者是炎症反应的可靠标志。与闭锁卵泡数目增加一致，BPA暴露的斑马鱼卵巢显示出升高的Bax / Bcl2比，caspase-8激活，-3和DNA分解，提示细胞死亡增加。重要的是，核雌激素受体（ER）转录本（esr1，esr2a和esr2b）的显着改变BPA暴露的卵巢中的蛋白质（ERα，ERβ），促性腺激素受体以及与类固醇生成和生长因子基因表达相关的标志物与卵巢功能受损和成熟反应密切相关。总体而言，氧化/亚硝化应激介导的炎症反应升高和内质网表达改变可影响暴露于BPA环境的生物的卵巢健康和生殖健康。