Mechanism of alcohol-induced impairment in renal development: Could it be reduced by retinoic acid?

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Abstract

1. Prenatal alcohol exposure impairs kidney development resulting in a reduced nephron number. However, the mechanism through which alcohol acts to disrupt renal development is largely unknown. Retinoic acid is critically involved in kidney development and it has been proposed that a diminished concentration is a contributing factor to fetal alcohol syndrome. 2. In this study we proposed that the ethanol-induced inhibition of ureteric branching morphogenesis and glomerular development in the cultured rat kidney would be ameliorated by co-culture with exogenous retinoic acid, and that examining the expression profile of key genes involved in the development of the kidney would provide insights into potential molecular pathways involved. 3. Whole rat metanephroi cultured in the presence of exogenous retinoic acid without ethanol appeared larger and had significantly more ureteric branch points, tips and glomeruli than metanephroi cultured in control media. Those cultured in the presence of ethanol alone (0.2 ) had 20 fewer ureteric branch points, tips and glomeruli, which was ameliorated by co-culture with retinoic acid. 4. Gene expression analysis identified changes in the expression levels of enzymes involved in the metabolism of alcohol, in conjunction with changes in key regulators of kidney development including cRET. 5. These results demonstrate that the teratogenic effects of alcohol in vitro on kidney development resulting in reduced ureteric branching morphogenesis and glomerular development can be ameliorated through co-culture with retinoic acid. These results provide the foundation for future research into the mechanism through which alcohol acts to disrupt kidney development.
Original languageEnglish
Pages (from-to)807 - 813
Number of pages7
JournalClinical and Experimental Pharmacology and Physiology
Volume39
Issue number9
DOIs
Publication statusPublished - 2012

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