Prenatal exposure to alcohol reduces nephron number and raises blood pressure in progeny.
Prenatal ethanol exposure is teratogenic, but the effects of ethanol on kidney development and the health of offspring are incompletely understood. Our objective was to investigate the effects of acute ethanol exposure during pregnancy on nephron endowment, mean arterial pressure, and renal function in offspring. We administered ethanol or saline by gavage to pregnant Sprague-Dawley rats on embryonic days 13.5 and 14.5. At 1 month of age, the nephron number was 15% lower and 10% lower in ethanol-exposed males and females, respectively, compared with controls. Mean arterial pressure, measured in conscious animals via indwelling tail-artery catheter, was 10% higher in both ethanol-exposed males and females compared with controls. GFR was 20% higher in ethanol-exposed males but 15% lower in ethanol-exposed females; moreover, males had increased proteinuria compared with controls. Furthermore, embryonic kidneys cultured in the presence of ethanol for 48 hours had 15% fewer ureteric branch points and tips than kidneys cultured in control media. Taken together, these data demonstrate that acute prenatal ethanol exposure reduces the number of nephrons, possibly as a result of inhibited ureteric branching morphogenesis, and that these changes affect adult cardiovascular and renal function.
Gray
Stephen P
SP
Department of Anatomy, Monash University, Clayton, Victoria, Australia.
Denton
Kate M
KM
Cullen-McEwen
Luise
L
Bertram
John F
JF
Moritz
Karen M
KM
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000196:embryology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009399:Nephrons / Q000196:embryology / Q000473:pathology* / Q000503:physiopathology*; D009929:Organ Size / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017597:Renal Blood Flow, Effective / Q000502:physiology
D000431:Ethanol