Department of Anatomy, Monash University, Clayton, Victoria, Australia.
J Am Soc Nephrol. 2010 Nov;21(11):1891-902. doi: 10.1681/ASN.2010040368. Epub 2010 Sep 9.
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.
产前乙醇暴露具有致畸性,但乙醇对肾脏发育和后代健康的影响尚不完全清楚。我们的目的是研究妊娠期间急性乙醇暴露对后代肾单位数量、平均动脉压和肾功能的影响。我们在胚胎第 13.5 和 14.5 天通过灌胃给予乙醇或生理盐水处理怀孕的 Sprague-Dawley 大鼠。在 1 个月大时,与对照组相比,乙醇暴露的雄性和雌性大鼠的肾单位数量分别降低了 15%和 10%。通过留置尾动脉导管在清醒动物中测量的平均动脉压,在乙醇暴露的雄性和雌性大鼠中均比对照组高 10%。乙醇暴露的雄性大鼠的 GFR 升高了 20%,而乙醇暴露的雌性大鼠的 GFR 降低了 15%;此外,雄性大鼠的蛋白尿比对照组增加。此外,与在对照培养基中培养的肾脏相比,在乙醇中培养 48 小时的胚胎肾脏的输尿管分支点和尖端减少了 15%。综上所述,这些数据表明急性产前乙醇暴露减少了肾单位的数量,这可能是由于输尿管分支形态发生受到抑制所致,这些变化会影响成年期心血管和肾功能。