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孕期低至中等剂量乙醇摄入的啮齿动物模型:乙醇摄入模式及其对胎儿和子代生长的影响

A rodent model of low- to moderate-dose ethanol consumption during pregnancy: patterns of ethanol consumption and effects on fetal and offspring growth.

作者信息

Probyn Megan E, Zanini Simone, Ward Leigh C, Bertram John F, Moritz Karen M

机构信息

School of Biomedical Sciences, The University of Queensland, St Lucia, Qld 4072, Australia.

出版信息

Reprod Fertil Dev. 2012;24(6):859-70. doi: 10.1071/RD11200.

Abstract

It is unknown whether low to moderate maternal alcohol consumption adversely affects postnatal health. The aim of the present study was to develop a rodent model of low-moderate-dose prenatal ethanol (EtOH) exposure. Sprague-Dawley rats were fed a liquid diet with or without 6% v/v EtOH throughout gestation and the pattern of dietary consumption determined. Fetal bodyweights and hepatic alcohol-metabolising gene expression were measured on embryonic Day (E) 20 and offspring growth studied until 1 year. At E8 the plasma EtOH concentration was 0.03%. There was little difference in dietary consumption between the two treatment groups. At E20, EtOH-exposed fetuses were significantly lighter than controls and had significantly decreased ADH4 and increased CYP2E1 gene expression. Offspring killed on postnatal Day (PN) 30 did not exhibit any growth deficits. Longitudinal repeated measures of offspring growth demonstrated slower growth in males from EtOH-fed dams between 7 and 12 months of age; a cohort of male pups killed at 8 months of age had a reduced crown-rump length and kidney weight. In conclusion, a liquid diet of 6% v/v EtOH fed to pregnant dams throughout gestation caused a 3-8% reduction in fetal growth and brain sparing, with growth differences observed in male offspring later in life. This model will be useful for future studies on the effects of low-moderate EtOH on the developmental origins of health and disease.

摘要

孕期低至中度饮酒是否会对产后健康产生不利影响尚不清楚。本研究的目的是建立一个低中剂量产前乙醇(EtOH)暴露的啮齿动物模型。在整个妊娠期,给Sprague-Dawley大鼠喂食含或不含6% v/v EtOH的液体饮食,并确定饮食消耗模式。在胚胎第20天(E20)测量胎儿体重和肝脏酒精代谢基因表达,并对后代生长进行研究直至1岁。在E8时,血浆EtOH浓度为0.03%。两个治疗组之间的饮食消耗差异不大。在E20时,暴露于EtOH的胎儿明显比对照组轻,ADH4基因表达显著降低,CYP2E1基因表达增加。在出生后第30天(PN30)处死的后代没有表现出任何生长缺陷。对后代生长的纵向重复测量表明,来自喂食EtOH的母鼠的雄性后代在7至12个月龄时生长较慢;一组在8个月龄时处死的雄性幼崽的顶臀长度和肾脏重量减少。总之,在整个妊娠期给怀孕母鼠喂食6% v/v EtOH的液体饮食会导致胎儿生长减少3-8%,出现脑保护现象,并且在雄性后代后期生活中观察到生长差异。该模型将有助于未来关于低中剂量EtOH对健康和疾病发育起源影响的研究。

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