Department of Physiology, The University of Melbourne, Parkville, VIC 3010, Australia.
FASEB J. 2012 Oct;26(10):4337-47. doi: 10.1096/fj.12-210401. Epub 2012 Jul 6.
Uteroplacental insufficiency is associated with adult cardiorenal and metabolic diseases, particularly in males. Pregnancy is the greatest physiological challenge facing women, and those born small are at increased risk of gestational hypertension and diabetes and delivering smaller babies. Increased maternal age is associated with exacerbated pregnancy complications. We hypothesized that pregnancy in aged, growth-restricted females unmasks an underlying predisposition to cardiorenal and metabolic dysfunction and compromises fetal growth. Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (restricted group) or sham surgery (control group) on d 18 of gestation in Wistar Kyoto rats. At 12 mo, growth-restricted F1 female offspring were mated with a normal male. F1 restricted females had elevated systolic blood pressure, before and during pregnancy (+10 mmHg) but normal renal and metabolic pregnancy adaptations. F2 fetal weight was not different between groups. In control and restricted females, advanced maternal age (12 vs. 4 mo) was associated with a reduction in the hypoglycemic response to pregnancy and reduced F2 fetal litter size and body weight. Aged rats born small exhibited mostly normal pregnancy adaptations, although they had elevated blood pressure. Advanced maternal age was associated with poorer fetal outcomes that were not exacerbated by low maternal birth weight.
胎盘功能不全与成人心脏、肾脏和代谢疾病有关，尤其是男性。怀孕是女性面临的最大生理挑战，出生体重较轻的女性患妊娠高血压和糖尿病以及胎儿体重较轻的风险增加。产妇年龄的增加与妊娠并发症的恶化有关。我们假设，老年、生长受限的雌性怀孕会揭示出潜在的心脏、肾脏和代谢功能障碍倾向，并影响胎儿生长。在妊娠第 18 天，通过双侧子宫血管结扎（限制组）或假手术（对照组）诱导胎盘功能不全。在 12 个月时，生长受限的 F1 雌性后代与正常雄性交配。F1 限制组雌性在怀孕前和怀孕期间的收缩压升高（+10mmHg），但肾脏和代谢妊娠适应性正常。两组之间的 F2 胎儿体重没有差异。在对照组和限制组中，高龄（12 个月对 4 个月）与对妊娠的低血糖反应降低以及 F2 胎儿窝产仔数和体重降低有关。出生体重较轻的老年大鼠表现出大部分正常的妊娠适应性，尽管它们的血压升高。高龄与较差的胎儿结局有关，但与低出生体重无关。
