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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/R568    most recent 90316.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Gray, S. P. Articles by Moritz, K. M. Search for Related Content PubMed PubMed Citation Articles by Gray, S. P. Articles by Moritz, K. M.

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

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

Departments of ¹Anatomy and Developmental Biology and ²Physiology, Monash University, Clayton, Australia; ³School of Biomedical Sciences and ⁴Centre for Chronic Disease, Central Clinical School, University of Queensland, St. Lucia, Australia; ⁵Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Canada; and ⁶Department of Pharmacology and Toxicology, Queen's University, Kingston, Canada

Submitted 26 March 2008 ; accepted in final form 13 June 2008

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.

nephron number; kidney; fetus; ethanol exposure; sheep