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Prenatal prednisone exposure disturbs fetal kidney development and its characteristics.

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Title: Prenatal prednisone exposure disturbs fetal kidney development and its characteristics.
Authors: Xia, Zhiping1,2 (AUTHOR), Wang, Songdi1,2 (AUTHOR), Wang, Wen1,2 (AUTHOR), Liu, Yutang1,2 (AUTHOR), Yang, Tianshu1,2 (AUTHOR), Wang, Hui1,2 (AUTHOR), Ao, Ying1,2 (AUTHOR) yingao@whu.edu.cn
Source: Journal of Environmental Sciences (Elsevier). Nov2024, Vol. 145, p75-87. 13p.
Subject Terms: Fetus, Kidney development, Dysplasia, Kidneys, Fetal development, Glial cell line-derived neurotrophic factor, Prenatal exposure, Kidney tubules, Notch signaling pathway
Abstract: • PPE inhibited the development of glomeruli and promoted compensatory growth of renal tubules. • PPE at clinical dose disturbed fetal kidney development with a time-effect difference, manifested as full-term pregnancy exposure > early pregnancy exposure > mid-late pregnancy exposure. • The developmental toxicity of PPE on fetal kidney was more serious to the female fetuses than the males. 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. Pregnant women may be exposed to prednisone actively or passively through multiple 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. [Display omitted] [ABSTRACT FROM AUTHOR]
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Abstract:• PPE inhibited the development of glomeruli and promoted compensatory growth of renal tubules. • PPE at clinical dose disturbed fetal kidney development with a time-effect difference, manifested as full-term pregnancy exposure > early pregnancy exposure > mid-late pregnancy exposure. • The developmental toxicity of PPE on fetal kidney was more serious to the female fetuses than the males. 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. Pregnant women may be exposed to prednisone actively or passively through multiple 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. [Display omitted] [ABSTRACT FROM AUTHOR]
ISSN:10010742
DOI:10.1016/j.jes.2023.09.042