Department of Physiology, The University of Melbourne, Parkville, VIC 3010, Australia.
J Physiol. 2012 Feb 1;590(3):617-30. doi: 10.1113/jphysiol.2011.219147. Epub 2011 Dec 5.
Intrauterine growth restriction caused by uteroplacental insufficiency increases risk of cardiovascular and metabolic disease in offspring. Cardio-renal and metabolic responses to pregnancy are critical determinants of immediate and long-term maternal health. However, no studies to date have investigated the renal and metabolic adaptations in growth restricted offspring when they in turn become pregnant. We hypothesised that the physiological challenge of pregnancy in growth restricted females exacerbates disease outcome and compromises next generation fetal growth. Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on day 18 of gestation in WKY rats and F1 female offspring birth and postnatal body weights were recorded. F1 Control and Restricted females were mated at 4 months and blood pressure, renal and metabolic parameters were measured in late pregnancy and F2 fetal and placental weights recorded. Age-matched non-pregnant Control and Restricted F1 females were also studied. F1 Restricted females were born 10-15% lighter than Controls. Basal insulin secretion and pancreatic β-cell mass were reduced in non-pregnant Restricted females but restored in pregnancy. Pregnant Restricted females, however, showed impaired glucose tolerance and compensatory glomerular hypertrophy, with a nephron deficit but normal renal function and blood pressure. F2 fetuses from Restricted mothers exposed to physiological measures during pregnancy were lighter than Controls highlighting additive adverse effects when mothers born small experience stress during pregnancy. Female rats born small exhibit mostly normal cardio-renal adaptations but altered glucose control during late pregnancy making them vulnerable to lifestyle challenges.
由胎盘功能不全引起的宫内生长受限增加了后代患心血管和代谢疾病的风险。对妊娠的心肺和代谢反应是母婴即时和长期健康的关键决定因素。然而，迄今为止，还没有研究过当生长受限的后代再次怀孕时，它们的肾脏和代谢适应情况。我们假设，生长受限雌性在妊娠期间的生理挑战会使疾病恶化，并损害下一代胎儿的生长。在 WKY 大鼠妊娠第 18 天通过双侧子宫血管结扎（受限）或假手术（对照）诱导胎盘功能不全，并记录 F1 代雌性后代的出生体重和产后体重。在 4 个月时，将 F1 对照和受限雌性进行交配，并在妊娠晚期测量血压、肾脏和代谢参数，并记录 F2 胎儿和胎盘的重量。还研究了年龄匹配的未怀孕的对照和受限的 F1 雌性。F1 受限雌性的出生体重比对照雌性轻 10-15%。未怀孕的受限雌性的基础胰岛素分泌和胰岛β细胞质量减少，但在妊娠时恢复。然而，怀孕的受限雌性表现出葡萄糖耐量受损和代偿性肾小球肥大，伴有肾单位缺陷，但肾功能和血压正常。来自受限母亲的 F2 胎儿在怀孕期间暴露于生理测量值时比对照组轻，这突出了当出生体重较轻的母亲在怀孕期间承受压力时，会产生累加的不利影响。出生体重较小的雌性大鼠主要表现出正常的心肺适应，但在妊娠晚期出现葡萄糖控制异常，使它们容易受到生活方式的挑战。
