Prenatal prednisone exposure disturbs fetal kidney development and its characteristics |
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Affiliation: | Department of Pharmacology,Wuhan University School of Basic Medical Sciences,Wuhan 430071,China;Hubei Provincial Key Laboratory of Developmentally Originated Disease,Wuhan 430071,China |
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Abstract: | Prednisone is a synthetic glucocorticoid that is commonly used in both human and vet-erinary medication.Now,it is also recognized as an emerging environmental contaminant.Pregnant women may be exposed to prednisone actively or passively through multiple path-ways and cause developmental toxicity to the fetus.However,the impact of prenatal pred-nisone exposure(PPE)on fetal kidney development remains unclear.In this study,pregnant mice were administered prednisone intragastrically during full-term pregnancy with differ-ent 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 re-duced 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 sig-naling 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. |
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Keywords: | Prenatal prednisone exposure Kidney developmental toxicity Glomerulus Toxicity characteristics |
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