Repeated ethanol exposure during late gestation decreases nephron endowment in fetal sheep.
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 approximately 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.
Gray
Stephen P
SP
Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800 Australia. Stephen.gray@med.monash.edu.au
Kenna
Kelly
K
Bertram
John F
JF
Hoy
Wendy E
WE
Yan
Edwin B
EB
Bocking
Alan D
AD
Brien
James F
JF
Walker
David W
DW
Harding
Richard
R
Moritz
Karen M
KM
D000653:Amniotic Fluid / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D020567:Fetal Weight / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005865:Gestational Age; D007262:Infusions, Intravenous; D007678:Kidney Glomerulus / Q000187:drug effects / Q000196:embryology; D009399:Nephrons / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep
D012333:RNA, Messenger; D000431:Ethanol