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ItemNo Preview AvailableCardio-renal and metabolic adaptations during pregnancy in female rats born small: implications for maternal health and second generation fetal growthGallo, LA ; Tran, M ; Moritz, KM ; Mazzuca, MQ ; Parry, LJ ; Westcott, KT ; Jefferies, AJ ; Cullen-McEwen, LA ; Wlodek, ME (WILEY, 2012-02-01)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.
ItemPregnancy in aged rats that were born small: cardiorenal and metabolic adaptations and second-generation fetal growthGallo, LA ; Tran, M ; Moritz, KM ; Jefferies, AJ ; Wlodek, ME (FEDERATION AMER SOC EXP BIOL, 2012-10-01)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.
ItemEffect of Pregnancy for Females Born Small on Later Life Metabolic Disease RiskTran, M ; Gallo, LA ; Wadley, GD ; Jefferies, AJ ; Moritz, KM ; Wlodek, ME ; He, B (PUBLIC LIBRARY SCIENCE, 2012-09-13)There is a strong inverse relationship between a females own birth weight and her subsequent risk for gestational diabetes with increased risk of developing diabetes later in life. We have shown that growth restricted females develop loss of glucose tolerance during late pregnancy with normal pancreatic function. The aim of this study was to determine whether growth restricted females develop long-term impairment of metabolic control after an adverse pregnancy adaptation. Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) in late pregnancy (E18) in F0 female rats. F1 Control and Restricted female offspring were mated with normal males and allowed to deliver (termed Ex-Pregnant). Age-matched Control and Restricted Virgins were also studied and glucose tolerance and insulin secretion were determined. Pancreatic morphology and hepatic glycogen and triacylglycerol content were quantified respectively. Restricted females were born lighter than Control and remained lighter at all time points studied (p<0.05). Glucose tolerance, first phase insulin secretion and liver glycogen and triacylglycerol content were not different across groups, with no changes in β-cell mass. Second phase insulin secretion was reduced in Restricted Virgins (-34%, p<0.05) compared to Control Virgins, suggestive of enhanced peripheral insulin sensitivity but this was lost after pregnancy. Growth restriction was associated with enhanced basal hepatic insulin sensitivity, which may provide compensatory benefits to prevent adverse metabolic outcomes often associated with being born small. A prior pregnancy was associated with reduced hepatic insulin sensitivity with effects more pronounced in Controls than Restricted. Our data suggests that pregnancy ameliorates the enhanced peripheral insulin sensitivity in growth restricted females and has deleterious effects for hepatic insulin sensitivity, regardless of maternal birth weight.