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This Article Full Text Full Text (PDF) All Versions of this Article: 572/1/67    most recent jphysiol.2006.106872v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cox, L. A. Articles by Nathanielsz, P. W. Search for Related Content PubMed PubMed Citation Articles by Cox, L. A. Articles by Nathanielsz, P. W. Related Collections Integrative

¹ Department of Genetics, Southwest Foundation for Biomedical Research, 7620 NW Loop 410, San Antonio, TX 78227-5301, USA
² Department of Genetics
³ Department of Physiology & Medicine
⁴ Department of Comparative Medicine
⁵ Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, TX 78227, USA
⁶ Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX 78229, USA

Previous studies in rodents and sheep show that maternal nutrient restriction during pregnancy alters fetal renal development. To date, no studies using fetal baboon RNA with human Affymetrix gene chips have been published. In the present study we have (1) evaluated the specificity of the Affymetrix human gene array ‘Laboratory on a Chip’ system for use with fetal baboon mRNA and (2) investigated the effects of moderate maternal global nutrient restriction (NR; 70% of ad libitum animals) from early (30 days gestation (dG)) to mid-gestation (90 dG; term = 184 dG) on the fetal baboon kidney. Morphometric and blood measurements were made on 12 non-pregnant baboons before they were bred. All baboons were fed ad libitum until 30 days pregnant, at which time six control baboons continued to feed ad libitum (control – C) while six received 70% of the C diet on a weight adjusted basis. Fetal kidneys were collected following caesarean section at 90 dG, with samples flash frozen and fixed for histological assessment. Fetal hip circumference was decreased in the NR group (68 ± 2 versus 75 ± 2 mm), while fetal body weight and all other measurements of fetal size were not different between C and NR at 90 dG. Maternal body weight was decreased in the NR group (12.16 ± 0.34 versus 13.73 ± 0.55 kg). Having established the specificity of the Affymetrix system for fetal baboon mRNA, gene expression profiling of fetal kidneys in the context of our maternal nutrient restriction protocol shows that NR resulted in a down-regulation of genes in pathways related to RNA, DNA and protein biosynthesis, metabolism and catabolism. In contrast, genes in cell signal transduction, communication and transport pathways were up-regulated in the NR group. These changes indicate that even a moderate level of maternal global NR impacts fetal renal gene pathways. Our histological assessment of renal structure indicates decreased tubule density within the cortex of NR kidneys compared with controls. The number of glomerular cross-sections per unit area were unaffected by NR, suggesting that tubule tortuosity and/or tubule length was decreased in the NR kidney. Taken together the changes indicate that NR results in accelerated fetal renal differentiation. The negative impact of poor maternal nutrition on the fetal kidney may therefore be in part due to shortening of critical phases of renal growth resulting in decreased functional capacity in later life. These findings may have important implications for postnatal renal function, thereby contributing to the observed increased predisposition to hypertension and renal disease in the offspring of nutrient restricted mothers.

(Received 3 February 2006; accepted after revision 23 February 2006; first published online 2 March 2006)
Corresponding author L. A. Cox: Department of Genetics, Southwest Foundation for Biomedical Research, 7620 NW Loop 410, San Antonio, TX 78227-5301, USA. Email: lcox{at}darwin.sfbr.org

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