Presented at the Neonatal Society 2003 Spring Meeting.
Brennan K1, Gopalakrishnan G1, Rhind SM2, Kyle CE2, Brooks AN3, Rae MT2, Stephenson T1, Olson D4, Symonds ME1
1 Academic Division of Child Health, School of Human Development, Queen’s Medical Centre, Nottingham, NG7 2UH, UK
2 Macaulay Institute, Craigiebuckler, Aberdeen, AB15 8QH,UK
3 Astrazeneca, Alderly Park, Cheshire, SK10 4TJ, UK
4 Perinatal Research Centre, University of Alberta, Edmonton, Canada
Introduction: The risk of developing hypertension later in life can be influenced by maternal nutrient intake, for which reduced fetal nutrition can adversely affect kidney development (1). Nutrient delivery to the fetus regulates levels of both IGF-I and its receptor (R). The aim of this study was therefore to determine the extent to which maternal nutrient restriction at specific stages of early and mid gestation might result in altered expression of IGF-IR within the fetal kidney.
Study design: Thirty-four singleton bearing Scottish Blackface ewes were individually housed from the day of mating and assigned to one of five nutritional groups (n=3-7). All ewes were fed a diet which was sufficient to meet 100% of total metabolisable energy requirements for that stage of gestation, then restricted to 50% between 0-30, 31-65, 66-110 and 0-110 days gestation. At 110 days gestation (ovine term is 147 days) all ewes were euthanased and fetal kidneys sampled. Total RNA was extracted from the fetal tissue and reverse transcribed. This cDNA was then used in PCR reactions using oligonucleotide primers specific for the IGF-IR and an 18S control. Abundance was measured using densitometry and the results calculated as a ratio of the IGF-IR reaction to the 18S reaction, then expressed as a percentage of a single reference sample in arbitrary units. Results were analysed using a Kruskal-Wallis test then each experimental group was compared to the control using a Mann-Whitney test.
Results:
Conclusion: This study found that the expression of IGF-1R is upregulated in the fetal kidney when maternal nutrition is targeted to the period between 66-110 days gestation when smaller kidneys resulted. This timing coincides with the period in kidney development when most nephrons are formed, a process in which IGF-I has an important role (2). It would appear that the transition from sufficient to restricted feed is important since those animals restricted from conception did not show the same response
References
1. Whorwood C et al Endocrinology 2001;142:2854-2864
2. Rogers S et al Developmental Genetics 1999;24:293-298