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妊娠和哺乳期的外源性雌激素暴露会破坏沙鼠母体乳腺在退化过程中的形态和炎症方面。

Gestational and lactational xenoestrogen exposure disrupts morphology and inflammatory aspects in mammary gland of gerbil mothers during involution.

机构信息

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.

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; Department of Histology, Embryology and Cell Biology, Institute of Biological Sciences, Federal University of Goiás (UFG), Avenida Esperança, s/n, Câmpus Samambaia, 74690-900 Goiânia, Goiás, Brazil.

出版信息

Environ Toxicol Pharmacol. 2022 Jan;89:103785. doi: 10.1016/j.etap.2021.103785. Epub 2021 Dec 9.

Abstract

In the mammary gland (MG), the developmental window for gestational/lactational differentiation and growth is highly vulnerable to hormonal disruption. Here we describe that the MG involution process in female gerbil mothers is delayed by bisphenol A (BPA) exposure during gestation and lactation. The process is directly influenced by changes in expression of extracellular matrix proteases MMP-2, MMP-9, and FAP, and the incidence of collagen and elastin is reduced after 7 and 14 days of weaning. A pro-inflammatory environment in the late involution process was confirmed by higher expression of TNF-α, COX-2 and phospho-STAT3 n the MG stroma, allied to increases in the incidence of macrophages and mast cells. These aspects impacted the proliferative pattern of epithelial cells, which decreased on the 14th post-weaning day. These data confirm that the milk production window of susceptibility is vulnerable to the impact of BPA, which promotes a suggestive pro-tumoral microenvironment during mammary involution.

摘要

在乳腺(MG)中,妊娠/哺乳期分化和生长的发育窗口期极易受到激素干扰。在这里,我们描述了在妊娠和哺乳期暴露于双酚 A(BPA)会延迟雌性沙鼠母亲的乳腺退化过程。这个过程直接受到细胞外基质蛋白酶 MMP-2、MMP-9 和 FAP 表达变化的影响,并且在断奶后 7 天和 14 天,胶原和弹性蛋白的发生率降低。在晚期退化过程中,通过 MG 基质中 TNF-α、COX-2 和磷酸化 STAT3 的更高表达证实了炎症前环境,同时巨噬细胞和肥大细胞的发生率增加。这些方面影响了上皮细胞的增殖模式,在断奶后第 14 天减少。这些数据证实,易感性的产奶窗口期易受 BPA 的影响,BPA 在乳腺退化过程中促进了一种提示性的促肿瘤微环境。

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