Endocrine Disruption and Reproductive Toxicology (EDART) Laboratory, SRM Institute of Science and Technology, Tamil Nadu, India.
Endocrine Disruption and Reproductive Toxicology (EDART) Laboratory, SRM Institute of Science and Technology, Tamil Nadu, India; Endocrine and Exposome (E2) Laboratory, Department of Zoology, Madras Christian College, Tamil Nadu, India.
Food Chem Toxicol. 2020 Aug;142:111442. doi: 10.1016/j.fct.2020.111442. Epub 2020 May 22.
Bisphenol-A (BPA) is one of the extensively studied estrogenic endocrine disrupting chemicals (EDC) with ubiquitous exposure among humans and wildlife. While there are literature reporting the association of dysregulated Brain-derived neurotrophic factor (BDNF) expression levels with altered cognitive and emotional behaviour such as anxiety-like and stress behaviour in animal models, there are no studies in BPA that investigate these altered neurobehavioural outcomes in parallel with the expression of intracellular proteins involved in BDNF signaling pathway. In this study, pregnant Wistar rats were exposed to BPA through water (25 μg/L, 250 μg/L, and 2.5 mg/L) during gestation day (GD) 9-21. Prenatal BPA exposure, increased anxiety-like behaviour in males and decreased exploratory behaviour in both male and female offspring. Downregulation of both BDNF and CYP19A1 genes were observed in male BPA-exposed offspring, whereas in females, the expression was upregulated. The expression of p-AKT, p-MEK and p-ERK proteins were increased in males, while in females, it decreased. Both the male and the female BPA-exposed offspring exhibited elevated levels of DNMT1 protein. The sex-specific alteration in the expression of CYP19A1 and DNA methyltransferase 1 (DNMT1) suggests that both hormonal and epigenetic dysregulation could underlie the long-term BPA-induced effect on anxiety-like behaviour in the offspring.
双酚 A（BPA）是一种广泛研究的具有雌激素活性的内分泌干扰化学物质（EDC），在人类和野生动物中普遍存在暴露。虽然有文献报道，脑源性神经营养因子（BDNF）表达水平的失调与动物模型中的认知和情绪行为改变有关，如焦虑样和应激行为，但在 BPA 中，没有研究调查这些改变的神经行为结果与参与 BDNF 信号通路的细胞内蛋白的表达平行。在这项研究中，妊娠 Wistar 大鼠在妊娠第 9-21 天通过饮水（25μg/L、250μg/L 和 2.5mg/L）暴露于 BPA 中。产前 BPA 暴露增加了雄性的焦虑样行为，减少了雄性和雌性后代的探索行为。雄性 BPA 暴露后代的 BDNF 和 CYP19A1 基因表达下调，而雌性后代的表达上调。雄性 p-AKT、p-MEK 和 p-ERK 蛋白的表达增加，而雌性的表达减少。雄性和雌性 BPA 暴露后代的 DNMT1 蛋白水平升高。CYP19A1 和 DNA 甲基转移酶 1（DNMT1）的表达在性别上的改变表明，激素和表观遗传的失调可能是 BPA 长期诱导后代焦虑样行为的基础。
