Submitted on October 12, 2007
Accepted on May 13, 2008
Differential effects of maternal nutrient restriction through pregnancy on kidney development and later blood pressure control in the resulting offspring
Kathryn A Brennan1, Susan Kaufman2, Stephen W Reynolds3, Breanne T McCook3, Grace Kan3, Inge Christiaens4, Michael E. Symonds5*, and David M Olson6
1 Academic Division of Child Health, The University of Nottingham, Nottingham, United Kingdom; Perinatal Research Centre, University of Alberta, Canada
2 Perinatal Research Centre, University of Alberta, Canada; Department of Physiology, University of Alberta, Canada
3 Perinatal Research Centre, University of Alberta, Canada
4 Perinatal Research Centre, The University of Alberta, Canada
5 Academic Division of Child Health, School of Human Development, Nottingham NG7 2UH, United States
6 Ob/Gyn, Physiology, and Pediatrics, University of Alberta, Edmonton, Canada
* To whom correspondence should be addressed. E-mail: michael.symonds{at}nottingham.ac.uk.
The mechanisms whereby maternal nutritional manipulation through pregnancy result in altered blood pressure in the offspring may include changes in fetal and newborn and adult renal prostaglandin (PG) synthesis, metabolism and receptor expression. As the postnatal effects of nutrient restriction on the renal PG synthesis and receptor system during nephrogenesis in conjunction with nephron numbers and blood pressure have not been evaluated in the rat, the present study examined the effect of reducing maternal food intake by 50% of ad libitum through pregnancy on young male rats. Six control fed mothers and 8 nutrient restricted pregnant rats with single litter mates were used at each sampling time point, most of which occurred during nephrogenesis. Offspring of nutrient restricted dams were lighter from birth to 3 days. This was accompanied by reduced PGE2, with smaller kidneys up to 14 days. Nutrient restriction also decreased mRNA expression of the PG synthesis (PGHS-2) enzyme, had little effect on the PG receptors, and increased mRNA expression of the degradation enzyme (PGDH) during nephrogenesis and the glucocorticoid receptor in the adult kidney. These mRNA changes were normally accompanied by similar changes in protein. Nephron number was also reduced from 7 days up to adulthood when blood pressure (measured by telemetry) did not increase as much as in control offspring during the dark, active period. In conclusion, maternal nutrient restriction suppressed renal PG concentrations in the offspring, and this was associated with suppressed kidney growth and development, and decreased blood pressure.
