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Am J Physiol Regul Integr Comp Physiol (June 18, 2008). doi:10.1152/ajpregu.90316.2008
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Submitted on March 26, 2008
Revised on June 13, 2008
Accepted on June 13, 2008

Repeated Ethanol Exposure During Late Gestation Decreases Nephron Endowment in Fetal Sheep

Stephen P Gray1*, Kelly Kenna, John F Bertram1, Wendy E Hoy2, Edwin B Yan1, Alan D Bocking3, James F Brien, David W. Walker4, Richard Harding1, and Karen M Moritz2

1 Monash University
2 University of Queensland
3 University of Toronto
4 Monash University, School of Biomedical Sciences.

* To whom correspondence should be addressed. E-mail: stephen.gray{at}med.monash.edu.

Maternal alcohol consumption during pregnancy can affect fetal development, but little is known about effects on the developing kidney. Our objectives were to determine the effects of repeated ethanol exposure during the latter half of gestation on glomerular (nephron) number and expression of genes involved in renal development or function in the fetal kidney. Pregnant ewes received daily intravenous infusion of ethanol (0.75g/kg, n=5) or saline (control, n=5) over 1 hour from 95-133 days of gestational age (DGA). Maternal and fetal arterial blood samples were taken before and after the start of the daily ethanol infusions for determination of blood ethanol concentration (BEC). Necropsy was performed at 134 DGA and fetal kidneys collected for determination of total glomerular number using the physical disector/fractionator technique. Maximal maternal and fetal BECs of 0.12±0.01g/dL (mean±SEM) and 0.11±0.01g/dL, respectively, were reached 1 hour after starting maternal ethanol infusions. Ethanol exposure had no effect on fetal body weight, kidney weight or the expression of members of the renin-angiotensin system, insulin-like growth factors and sodium channels. However, fetal glomerular number was lower after ethanol exposure (377,585±8,325) than in controls (423,177±17,178, P<0.001). The data demonstrate that fetal ethanol exposure during the latter half of gestation results in an 11% reduction in nephron endowment, without affecting the overall growth of the kidney or fetus or the expression of key genes involved in renal development or function. A reduced nephron endowment of this magnitude could have important implications for the cardiovascular health of offspring during postnatal life.







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