Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", University of Salerno, 84081, Baronissi, SA, Italy.
Department of Movement Sciences and Wellbeing, Parthenope University of Naples, 80133, Naples, Italy.
Chemosphere. 2020 Sep;254:126819. doi: 10.1016/j.chemosphere.2020.126819. Epub 2020 Apr 18.
Bisphenol A (BPA) is a synthetic xenoestrogen diffused worldwide. Humans are chronically exposed to low doses of BPA from food and drinks, thus BPA accumulates in tissues posing human health risk. In this study, we investigated the effects of BPA on peripheral blood mononuclear cells (PBMC) from human healthy donors, and in glia and microglia of rat offspring at postnatal day 17 (17PND) from pregnant females who received BPA soon after coupling and during lactation and weaning. Results indicated that BPA affected Phytoemagglutinin (PHA) stimulated PBMC proliferation causing an S-phase cell cycle accumulation at nanomolar concentrations while BPA was almost ineffective in resting PBMC. Furthermore, BPA induced chromosome aberrations and the appearance of shattered cells characterized by high number of fragmented and pulverized chromosomes, suggesting that the compound could cause a massive genomic rearrangement by inducing catastrophic events. The BPA-induced DNA damage was observed mainly in TCD4+ and TCD8+ subsets of T lymphocytes and was mediated by the increase of ERK1/2 phosphorylation, p21/Waf1 and PARP1 protein expression. Intriguingly, we observed for the first time that BPA-induced effects were associated to a sex specific modulation of ERα and ERβ in human PBMC. Immunofluorescence analysis of rat hippocampus corroborated in vitro findings showing that BPA induced ɣH2AX phosphorylation in microglia and astrocytosis by decreasing ERα expression within the dentate gyrus. Overall these results suggest that BPA can alter immune surveillance functions at both peripheral and central level with a potential risk for cancer, neuroinflammation and neurodegeneration.
双酚 A（BPA）是一种广泛存在于世界各地的合成外源性雌激素。人类通过食物和饮料长期接触低剂量的 BPA，因此 BPA 在组织中积累，对人类健康构成风险。在这项研究中，我们研究了 BPA 对来自人类健康供体的外周血单个核细胞（PBMC）的影响，以及在怀孕母体在交配后和哺乳期接受 BPA 时，其子代在出生后第 17 天（17PND）的胶质细胞和小胶质细胞中的影响。结果表明，BPA 以纳米摩尔浓度影响植物血凝素（PHA）刺激的 PBMC 增殖，导致 S 期细胞周期积累，而在静止的 PBMC 中，BPA 几乎没有作用。此外，BPA 诱导染色体畸变和破碎细胞的出现，其特征是染色体高度碎裂和粉碎，表明该化合物可能通过诱导灾难性事件引起大量基因组重排。BPA 诱导的 DNA 损伤主要发生在 T 淋巴细胞的 TCD4+和 TCD8+亚群中，这是通过增加 ERK1/2 磷酸化、p21/Waf1 和 PARP1 蛋白表达来介导的。有趣的是，我们首次观察到 BPA 诱导的作用与人类 PBMC 中 ERα 和 ERβ 的性别特异性调节有关。对大鼠海马体的免疫荧光分析证实了体外研究结果，表明 BPA 通过降低齿状回内的 ERα 表达，诱导小胶质细胞和星形胶质细胞中的 ɣH2AX 磷酸化。总的来说，这些结果表明 BPA 可以改变外周和中枢水平的免疫监视功能，可能增加癌症、神经炎症和神经退行性变的风险。
