Mechanisms of impaired nephrogenesis with fetal growth restriction: altered renal transcription and growth factor expression

Abstract

Maternal food restriction during pregnancy results in growth-restricted newborns and reduced glomerular number, contributing to programmed offspring hypertension. We investigated whether reduced nephrogenesis may be programmed by dysregulation of factors controlling ureteric bud branching and mesenchyme to epithelial transformation. At 10 to 20 days' gestation, Sprague Dawley pregnant rats (n = 6/group) received ad libitum food; food-restricted rats were 50% food restricted. At embryonic day 20, messenger ribonucleic acid (mRNA) and protein expression of Wilms' tumor 1 gene product (WT1), paired box transcription factor (Pax)-2, fibroblast growth factor (FGF)-2, glial cell line-derived neurotrophic factor (GDNF), cRET, wingless-type mouse mammary tumor virus integration site (WNT)4, WNT11, bone morphogenetic protein (BMP)-4, BMP7, and FGF7 were determined by real-time polymerase chain reaction and Western blotting. Maternal food restriction resulted in up-regulated mRNA expression for WT1, FGF2, and BMP7, whereas Pax2, GDNF, FGF7, BMP4, WNT4, and WNT11 mRNAs were down-regulated. Protein expression was concordant for WT1, GDNF, Pax2, FGF7, BMP4, and WNT4. Maternal food restriction altered gene expression of fetal renal transcription and growth factors and likely contributes to development of offspring hypertension.