Department of Biology, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University (UNESP), Rua Cristóvão Colombo 2265, Jardim Nazareth, 15054-000 São José do Rio Preto, São Paulo, Brazil.
Federal University of São João del Rei, Campus Centro Oeste Dona Lindu, Avenida Sebastião Gonçalves Coelho, 400, Bairro Chanadour, 35501-296 Divinópolis, Minas Gerais, Brazil.
Exp Mol Pathol. 2020 Apr;113:104374. doi: 10.1016/j.yexmp.2020.104374. Epub 2020 Jan 7.
The endocrine disruptive effects caused by bisphenol A (BPA) are well known. Despite this, to date, evaluation of its long term effects is limited, meaning that there is still much to be unveiled in terms of alterations caused by perinatal exposure to BPA. Our aim was to determine if perinatal exposure to two different doses of BPA causes long term morphological and molecular alteration effects in the mammary gland (MG). We evaluated MG from Mongolian gerbil offspring exposed perinatally (during gestation and lactation) to 50 or 5000 μg/kg/day BPA. At 90 days of age the animals were subjected to a single dose of N-nitroso-N-methylurea in order to mimic a carcinogenic environment. At 6 months of age, animals in estrous were euthanized for morphological evaluation of the MGs. The MG architecture presented considerable changes in terms of detached epithelial cells, inflammation, glandular hyperplasia, and collagen fiber deposition. Furthermore, a higher index of epithelial cell proliferation was detected in comparison to the intact control group. In addition, we verified a higher molecular expression of EZH2 in the vehicle treated group, indicating that corn oil applied alone can alter the expression of this epigenetic biomarker. In conclusion, BPA perinatal exposure promotes significant changes in glandular cytoarchitecture and increases glandular epithelium proliferation rate, leading to the retention of stem-like properties. This event could compromise the fate and differentiation potential of mammary epithelium.
双酚 A(BPA)造成的内分泌干扰效应是众所周知的。尽管如此,迄今为止,其长期影响的评估仍然有限,这意味着在围产期暴露于 BPA 引起的改变方面仍有许多未解之谜。我们的目的是确定围产期暴露于两种不同剂量的 BPA 是否会导致乳腺(MG)的长期形态和分子改变效应。我们评估了蒙古沙鼠后代的 MG,这些后代在围产期(妊娠期和哺乳期)暴露于 50 或 5000μg/kg/天的 BPA 中。在 90 天时,动物接受了 N-亚硝基-N-甲基脲的单次剂量,以模拟致癌环境。在 6 个月大时,处于发情期的动物被安乐死,以对 MGs 进行形态学评估。MG 结构在脱落的上皮细胞、炎症、腺体增生和胶原纤维沉积方面表现出相当大的变化。此外,与完整对照组相比,检测到上皮细胞增殖指数更高。此外,我们还发现与载体处理组相比,EZH2 的分子表达更高,表明单独应用玉米油可以改变这种表观遗传生物标志物的表达。总之,围产期 BPA 暴露会导致腺体细胞结构发生重大变化,并增加腺体上皮细胞的增殖率,从而保留干细胞样特性。这一事件可能会影响乳腺上皮的命运和分化潜力。