Dodic Miodrag, Hantzis Vicky, Duncan Jhodie, Rees Sandra, Koukoulas Irene, Johnson Kelli, Wintour E Marelyn, Moritz Karen
Howard Florey Institute, University of Melbourne, Parkville 3010, Melbourne, Victoria, Australia.
FASEB J. 2002 Jul;16(9):1017-26. doi: 10.1096/fj.01-1045com.
Recent studies have linked fetal exposure to a suboptimal intrauterine environment with adult hypertension. The aims of this study were twofold: 1) to see whether cortisol treatment administered to the ewe for 2 days at 27 days of gestation (term approximately 150 days) resulted in high blood pressure in offspring; 2) to study the effect of the same treatment on gene expression in the brain at 130 days of gestation and in lambs at 2 months of age. Mean arterial pressure was significantly higher in the adult female and male offspring of sheep treated with cortisol than in the control group (females: 89+/-2 mmHg vs. 81+/-2; P<0.05 and males: 102+/-4 mmHg vs. 91+/-3; P<0.05). Prenatal cortisol treatment led to up-regulation of angiotensinogen, AT1, MR, and GR mRNA in the hippocampus in fetuses at 130 days of gestation but not in the animals at 2 months of age. This is the first evidence that short prenatal exposure to cortisol programmed high blood pressure in the adult female and male offspring of sheep. Altered gene expression in the hippocampus could have a significant effect on the development of the hippocampus, and on postnatal behavior.
近期研究已将胎儿暴露于次优宫内环境与成人高血压联系起来。本研究的目的有两个：1）观察在妊娠27天（足月约150天）给母羊连续2天注射皮质醇是否会导致后代高血压；2）研究相同处理对妊娠130天胎儿及2月龄羔羊大脑基因表达的影响。接受皮质醇处理的绵羊成年雌性和雄性后代的平均动脉压显著高于对照组（雌性：89±2 mmHg对81±2；P<0.05；雄性：102±4 mmHg对91±3；P<0.05）。产前皮质醇处理导致妊娠130天胎儿海马中血管紧张素原、AT1、MR和GR mRNA上调，但对2月龄动物无此影响。这是首次有证据表明产前短期暴露于皮质醇会使绵羊成年雌性和雄性后代出现高血压。海马中基因表达的改变可能对海马发育及出生后行为产生显著影响。
