Pregnancy in aged rats that were born small: cardiorenal and metabolic adaptations and second‐generation fetal growth

Linda A. Gallo, Melanie Tran, Karen M. Moritz, Andrew J. Jefferies, Mary E. Wlodek

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.