Harding R, Moritz KM. Repeated ethanol exposure during late gestation decreases nephron endowment in fetal sheep. Am J Physiol Regul Integr Comp Physiol 295: R568 -R574, 2008. First published June 18, 2008 doi:10.1152/ajpregu.90316.2008.-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 ϭ 5) or saline (control, n ϭ 5) over 1 h from 95 to 133 days of gestational age (DGA; term is ϳ147 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 Ϯ 0.01 g/dl (mean Ϯ SE) and 0.11 Ϯ 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 Ϯ 8,325) than in controls (423,177 Ϯ 17,178, P Ͻ 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 ALCOHOL (ETHANOL) CONSUMPTION during pregnancy remains common in most developed countries, but recommended guidelines on safe levels of alcohol consumption vary significantly (42). Excessive alcohol consumption during pregnancy is known to result in the fetal alcohol syndrome with characteristic craniofacial dysmorphology, growth restriction, and intellectual dysfunction as the principal diagnostic features manifesting after birth (13,30,34,48). Even moderate levels of alcohol exposure are now known to adversely affect learning and behavior in infants and children. While there is ample evidence that prenatal ethanol exposure can affect central nervous system development, few studies have investigated the effects on other critical organs, such as the kidney. Studies of children diagnosed with FAS demonstrate that some have renal malformations (32, 37); their kidneys are often small, misshapen, and freque...