Prenatal prednisone exposure disturbs fetal kidney development and its characteristics  

作　　者：Zhiping Xia Songdi Wang Wen Wang Yutang Liu Tianshu Yang Hui Wang Ying Ao 

机构地区：[1]Department of Pharmacology,Wuhan University School of Basic Medical Sciences,Wuhan 430071,China [2]Hubei Provincial Key Laboratory of Developmentally Originated Disease,Wuhan 430071,China

出　　处：《Journal of Environmental Sciences》2024年第11期75-87,共13页环境科学学报（英文版）

基　　金：supported by the National Key Research and Development Program of China(No.2020YFA0803900);the National Natural Science Foundation of China(No.81872943)。

摘　　要：Prednisone is a synthetic glucocorticoid that is commonly used in both human and veterinary medication.Now,it is also recognized as an emerging environmental contaminant.Pregnantwomenmay be exposed to prednisone actively or passively throughmultiple pathways and cause developmental toxicity to the fetus.However,the impact of prenatal prednisone exposure(PPE)on fetal kidney development remains unclear.In this study,pregnant mice were administered prednisone intragastrically during full-term pregnancy with different doses(0.25,0.5,or 1 mg/(kg·day)),or at the dose of 1 mg/(kg·day)in different gestational days(GD)(GD0-9,GD10-18,or GD0-18).The pregnant mice were euthanized on GD18.HE staining revealed fetal kidney dysplasia,with an enlarged glomerular Bowman’s capsule space and a reduced capillary network in the PPE groups.The expression of the podocyte and the mesangial cell marker genes was significantly reduced in the PPE groups.However,overall gene expression in renal tubules and collecting ducts were markedly increased.All of the above effects were more pronounced in high-dose,full-term pregnancy,and female fetuses.Studies on the mechanism of the female fetal kidney have revealed that PPE reduced the expression of Six2,increased the expression of Hnf1β,Hnf4α,and Wnt9b,and inhibited the expression of glial cell line-derived neurotrophic factor(GDNF)and Notch signaling pathways.In conclusion,this study demonstrated that there is a sex difference in the developmental toxicity of PPE to the fetal kidney,and the time effect is manifested as full-term pregnancy>early pregnancy>mid-late pregnancy.

关 键 词：Prenatal prednisone exposure Kidney developmental toxicity GLOMERULUS Toxicity characteristics 

分 类 号：X171.5[环境科学与工程—环境科学]