Repeated ethanol exposure during late gestation decreases nephron endowment in fetal sheep

Gray, Stephen P., Kenna, Kelly, Bertram, John F., Hoy, Wendy E., Yan, Edwin B., Bocking, Alan D., Brien, James F., Walker, David W., Harding, Richard and Moritz, Karen M. (2008) Repeated ethanol exposure during late gestation decreases nephron endowment in fetal sheep. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 295 2: R568-R574. doi:10.1152/ajpregu.90316.2008


Author Gray, Stephen P.
Kenna, Kelly
Bertram, John F.
Hoy, Wendy E.
Yan, Edwin B.
Bocking, Alan D.
Brien, James F.
Walker, David W.
Harding, Richard
Moritz, Karen M.
Title Repeated ethanol exposure during late gestation decreases nephron endowment in fetal sheep
Journal name American Journal of Physiology: Regulatory, Integrative and Comparative Physiology   Check publisher's open access policy
ISSN 0363-6119
1522-1490
Publication date 2008-08
Sub-type Article (original research)
DOI 10.1152/ajpregu.90316.2008
Volume 295
Issue 2
Start page R568
End page R574
Total pages 7
Place of publication Bethesda, U.S.A.
Publisher American Physiological Society
Collection year 2009
Language eng
Subject 11 Medical and Health Sciences
0606 Physiology
1116 Medical Physiology
C1
Formatted abstract
Maternal alcohol consumption during pregnancy can affect fetal development, but little is known about the 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 key genes involved in renal development or function in the ovine fetal kidney. Pregnant ewes received daily intravenous infusion of ethanol (0.75 g/kg, n = 5) or saline (control, n = 5) over 1 h from 95 to 133 days of gestational age (DGA; term is ~147 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 were collected for determination of total glomerular number using the physical disector/fractionator technique; at this gestational age nephrogenesis is completed in sheep. Maximal maternal and fetal BECs of 0.12 ± 0.01 g/dl (mean ± SE) and 0.11 ± 0.01 g/dl, respectively, were reached 1 h after starting maternal ethanol infusions. Ethanol exposure had no effect on fetal body weight, kidney weight, or the gene 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 our regimen of 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.
Copyright © 2008 the American Physiological Society
Keyword Nephron number
Kidney
Fetus
Ethanol exposure
Sheep
Q-Index Code C1
Q-Index Status Confirmed Code

 
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Created: Thu, 03 Sep 2009, 09:44:17 EST by Mr Andrew Martlew on behalf of School of Medicine