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孕期双酚A处理对小鼠肾脏发育的影响:一项体视学和组织病理学研究

Effects of bisphenol A treatment during pregnancy on kidney development in mice: a stereological and histopathological study.

作者信息

Nuñez P, Fernandez T, García-Arévalo M, Alonso-Magdalena P, Nadal A, Perillan C, Arguelles J

机构信息

1Departamento de Biología Funcional (Área de Fisiología), Facultad de Medicina y Ciencias de la Salud,Universidad de Oviedo,Asturias,Spain.

2Unidad de Histopatología Molecular en Modelos Animales de Cáncer, Facultad de Medicina y Ciencias de la Salud,Universidad de Oviedo,Asturias,Spain.

出版信息

J Dev Orig Health Dis. 2018 Apr;9(2):208-214. doi: 10.1017/S2040174417000939. Epub 2017 Nov 6.

Abstract

Bisphenol A (BPA) is a chemical found in plastics that resembles oestrogen in organisms. Developmental exposure to endocrine-disrupting chemicals, such as BPA, increases the susceptibility to type 2 diabetes (T2DM) and cardiovascular diseases. Animal studies have reported a nephron deficit in offspring exposed to maternal diabetes. The aim of this study was to investigate the prenatal BPA exposure effects on nephrogenesis in a mouse model that was predisposed to T2DM. This study quantitatively evaluated the renal structural changes using stereology and histomorphometry methods. The OF1 pregnant mice were treated with a vehicle or BPA (10 or 100 μg/kg/day) during days 9-16 of gestation (early nephrogenesis). The 30-day-old offspring were sacrificed, and tissue samples were collected and prepared for histopathological and stereology studies. Glomerular abnormalities and reduced glomerular formation were observed in the BPA offspring. The kidneys of the BPA10 and BPA100 female offspring had a significantly lower glomerular number and density than those of the CONTROL female offspring. The glomerular histomorphometry revealed a significant difference between the female and male CONTROL offspring for the analysed glomerular parameters that disappeared in the BPA10 and BPA100 offspring. In addition, the kidney histopathological examination showed typical male cuboidal epithelial cells of the Bowman capsule in the female BPA offspring. Exposure to environmentally relevant doses of BPA during embryonic development altered nephrogenesis. These structural changes could be associated with an increased risk of developing cardiometabolic diseases later in life.

摘要

双酚A(BPA)是一种存在于塑料中的化学物质,在生物体中类似于雌激素。发育期接触内分泌干扰化学物质,如双酚A,会增加患2型糖尿病(T2DM)和心血管疾病的易感性。动物研究报告称,暴露于母体糖尿病的后代存在肾单位缺陷。本研究的目的是在易患T2DM的小鼠模型中,研究产前双酚A暴露对肾发生的影响。本研究使用体视学和组织形态计量学方法定量评估了肾脏结构变化。在妊娠第9至16天(早期肾发生期),对OF1怀孕小鼠给予载体或双酚A(10或100μg/kg/天)处理。处死30日龄的后代,收集组织样本并制备用于组织病理学和体视学研究。在双酚A处理的后代中观察到肾小球异常和肾小球形成减少。双酚A 10和双酚A 100雌性后代的肾脏肾小球数量和密度显著低于对照雌性后代。肾小球组织形态计量学显示,对照雌性和雄性后代在分析的肾小球参数上存在显著差异,而在双酚A 10和双酚A 100后代中这种差异消失。此外,肾脏组织病理学检查显示,双酚A雌性后代的鲍曼囊中有典型的男性立方上皮细胞。胚胎发育期间暴露于环境相关剂量的双酚A会改变肾发生。这些结构变化可能与生命后期发生心脏代谢疾病的风险增加有关。

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