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. 2008 Sep;199(3):252.e1-7.
doi: 10.1016/j.ajog.2008.05.018. Epub 2008 Jul 17.

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

Ahmed K Abdel-Hakeem  1 , Tasmia Q Henry, Thomas R Magee, Mina Desai, Michael G Ross, Roy Z Mansano, John S Torday, Cynthia C Nast
Affiliations

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

Ahmed K Abdel-Hakeem et al. Am J Obstet Gynecol. 2008 Sep.

Abstract

Objective: 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.

Study design: 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.

Results: 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.

Conclusion: Maternal food restriction altered gene expression of fetal renal transcription and growth factors and likely contributes to development of offspring hypertension.

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Figures

Figure 1
Figure 1
Fetal kidney maternal FR mRNA expression. Fold change in mRNA expression compared with controls. Control fold = 1.0 *p<0.05, **p<0.01. Error bars represent SEM of the fold change.
Figure 2
Figure 2
Fetal kidney maternal FR protein expression. Fold change in protein expression compared with controls. Control fold = 1.0 *p<0.05, **p<0.01, ***p<0.001. Error bars represent SEM of the fold change.
Figure 3
Figure 3
Representative Western blots of fetal kidney maternal FR protein expression. Blots represented control samples (left hand panels) and FR samples (right hand panels). 4–6 pooled samples per blot.
See this image and copyright information in PMC

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