Journal of Kerman University of Medical Sciences

Maternal Ethanol Exposure Impairs the Kidney of Offspring by Alteration of Podocyte Proteins Genes Expression and Fibrosis

Document Type : Original Article

Authors

Farideh Nezami Majd 1
Alireza Shirpoor 1
Ali Taghizadeh Afshari 2
Fatemeh Kheradmand 2
Roya Naderi 2
Masoumeh Pourjabali 2
Yousef Rasmi 3

1 Nephrology and kidney Transplant Research Center, Urmia University of Medical Sciences, Urmia, Iran & Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

2 Nephrology and kidney Transplant Research Center, Urmia University of Medical Sciences, Urmia, Iran

3 Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

https://doi.org/10.34172/jkmu.2022.55
Abstract
Background: This study examined the effect of prenatal and early postnatal ethanol exposure on the structural, functional, and molecular alterations of rat’s offspring kidney on postnatal days 21 and 90.
Methods: Pregnant rats on gestation day 7 were divided into the two groups, namely control and ethanol groups. Rats in the ethanol group received ethanol (4.5 g/kg B.W) from gestation day 7 throughout lactation. Nephrin, podocin, vascular endothelial growth factor receptors (VEGFRs) 1 and 2 gene expression were measured by RT-PCR technique. The MMP2 and MMP9 levels in the kidney tissue and plasma cystatin C level were measured by ELISA method.
Results: The results revealed a significant alteration in mRNA expression of nephrin, podocin, and VEGFR, as well as MMPs amounts in the kidneys of the offspring. Cystatin C level, the ratio of cystatin C/serum creatinine, serum creatinine, and urine urea showed a significant increase, but urine creatinine and GFR showed a significant decrease in the offsprings of the ethanol group compared to the control group. Histopathological changes such as fibrosis, kidney cells proliferation, leukocytes infiltration, and vacuolization have also seen in the kidney of the offsprings after 21 and 90 days from birth.
Conclusion: Taken together, these results provide evidence that pre and early postnatal ethanol exposure renal toxicity is in part associated with alteration of nephrin, podocin, and VEGFRs genes expression, as well as MMPs amount changes. Furthermore, it was found that these molecular alterations were triggered by inflammatory reactions manifested by fibrosis, proliferation, and polymorphonuclear(PMN) leukocytes infiltration.

Keywords

Cystatin C
Ethanol
kidney
Matrix Metalloproteins
Nephrin
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Journal of Kerman University of Medical Sciences
Volume 29, Issue 5
September and October 2022
Pages 452-461

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