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


METHODS
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.


CONCLUSIONS
Maternal food restriction altered gene expression of fetal renal transcription and growth factors and likely contributes to development of offspring hypertension.
Abdel-Hakeem
Ahmed K
AK
Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Henry
Tasmia Q
TQ
Magee
Thomas R
TR
Desai
Mina
M
Ross
Michael G
MG
Mansano
Roy Z
RZ
Torday
John S
JS
Nast
Cynthia C
CC
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D031204:Caloric Restriction; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007668:Kidney / Q000196:embryology*; D051762:PAX2 Transcription Factor / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014513:Ureter / Q000196:embryology; D051153:Wnt Proteins / Q000378:metabolism; D060528:Wnt4 Protein
C525810:Bmp4 protein, mouse; C525811:Bmp4 protein, rat; C525821:Bmp7 protein, rat; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D036341:Intercellular Signaling Peptides and Proteins; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; C508957:Wnt11 protein, mouse; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; C555583:Wnt4 protein, rat; D016222:Fibroblast Growth Factor 2