This study was aimed to investigate the effect of prenatal ethanol exposure (PEE) on the susceptibility of offspring rats to glomerulosclerosis and to explore the mechanism. Pregnant Wistar rats were intragastrically administered ethanol (4g/kg·d) from gestational day (GD) 9 to GD 20, and the control group was given equal volume of normal saline. The offspring rats were all fed with high-fat diet after weaning, and were sacrificed at postnatal week 24 (PW24). The results revealed that the adult offspring kidneys in the male and female PEE groups exhibited higher glomerulosclerosis index and interstitial fibrosis index compared with the high-fat diet control groups, accompanied by elevated serum creatinine level. The protein expression of Nephrin and WT1, which were the marker genes of podocytes, was significantly decreased, whereas the protein expression of desmin and α-SMA, the marker genes of mesenchymal cells, was remarked enhanced in the male and female PEE groups. Compared with the high-fat diet control groups, the mRNA and protein expressions of renal angiotensin II receptor type 2 (AT2R) were decreased in the male PEE group, but increased in the female PEE group. PEE increased the mRNA and protein expressions of glucocorticoid (GC) activation system and inhibited the expression of insulin-like growth factor 1 (IGF1) signaling pathway in male offspring kidney; on the contrary, in female offspring kidney, PEE inhibited the mRNA and protein expression of glucocorticoid activation system and increased the expression of IGF1 signaling pathway. Taken together, PEE increased the susceptibility of the adult offspring to glomerulosclerosis, and the programming of renal AT2R or GC-IGF1 is respectively involved in the toxicity of PEE to the male or female offspring.

中文翻译：

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产前乙醇暴露增加成年后代大鼠肾小球硬化的易感性

本研究旨在探讨产前乙醇暴露（PEE）对子代大鼠肾小球硬化易感性的影响并探讨其机制。妊娠Wistar大鼠于妊娠第9～20日灌胃乙醇(4g/kg·d)，对照组给予等体积生理盐水。子代大鼠断奶后全部饲喂高脂饮食，并于产后第24周（PW24）处死。结果显示，与高脂饮食对照组相比，男性和女性 PEE 组的成年后代肾脏表现出更高的肾小球硬化指数和间质纤维化指数，并伴有血清肌酐水平升高。足细胞标记基因 Nephrin 和 WT1 的蛋白表达显着降低，而间充质细胞标记基因desmin和α-SMA的蛋白表达在男性和女性PEE组中显着增强。与高脂饮食对照组相比，男性PEE组肾血管紧张素II受体2型（AT2R）mRNA和蛋白表达降低，女性PEE组升高。PEE增加雄性子代肾脏糖皮质激素（GC）激活系统的mRNA和蛋白表达，抑制胰岛素样生长因子1（IGF1）信号通路的表达；相反，在雌性后代肾脏中，PEE抑制糖皮质激素激活系统的mRNA和蛋白表达，增加IGF1信号通路的表达。总之，PEE 增加了成年后代对肾小球硬化的易感性，