The current study aimed to explore whether bisphenol A (BPA) exposure aggravated the decrease in Tregs induced by ovalbumin (OVA) in adolescent female mouse models of asthma, and whether the process was associated with mTOR-mediated signaling pathways and DNA methylation levels. A total of 40 female C57BL/6 mice at the age of four weeks were used and divided into five groups after 1 week of domestication. Each group consisted of eight mice: the control group, OVA group, OVA + BPA (0.1 μg mL) group, OVA + BPA (0.2 μg mL) group, and OVA + BPA (0.4 μg mL) group. Results revealed that Foxp3 protein levels decreased in the spleens of mice exposed to BPA compared to those in the OVA group. After an elevation in BPA dose, the mRNAs of methyltransferases (, , and ) were gradually upregulated. The mechanism was related to the activity of TLR4/NF-κB and PI3K/Akt/mTOR signaling pathways and the enhancement of DNA methylation. Our results, collectively, provided a new view for studying the mechanisms underlying BPA exposure-induced immune dysfunction. Investigation of the regulatory mechanisms of DNA methylation in the abnormal Th immune response caused by BPA exposure could help reveal the causes and molecular mechanisms underlying the high incidence of allergic diseases in children in recent years.

中文翻译：

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双酚 A 诱导的 Treg 细胞减少与青春期小鼠脾脏中 PI3K/Akt/mTOR 信号通路和 Foxp3 DNA 甲基化的上调有关

本研究旨在探讨双酚A（BPA）暴露是否会加剧青春期雌性哮喘小鼠卵清蛋白（OVA）诱导的Treg细胞减少，以及该过程是否与mTOR介导的信号通路和DNA甲基化水平相关。总共使用40只4周龄雌性C57BL/6小鼠，驯化1周后分为5组。每组由8只小鼠组成：对照组、OVA组、OVA+BPA(0.1μg·mL-1)组、OVA+BPA(0.2μg·mL-1)组、OVA+BPA(0.4μg·mL-1)组。结果显示，与 OVA 组相比，暴露于 BPA 的小鼠脾脏中 Foxp3 蛋白水平降低。 BPA 剂量增加后，甲基转移酶 (、、和) 的 mRNA 逐渐上调。其机制与TLR4/NF-κB和PI3K/Akt/mTOR信号通路的活性以及DNA甲基化的增强有关。总的来说，我们的结果为研究 BPA 暴露引起的免疫功能障碍的机制提供了新的观点。探讨BPA暴露引起的Th免疫反应异常中DNA甲基化的调控机制，有助于揭示近年来儿童过敏性疾病高发的原因和分子机制。