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Pregnancy in aged rats that were born small: cardiorenal and metabolic adaptations and second-generation fetal growth
Linda A Gallo1, Melanie Tran, Karen M Moritz
1Department of Physiology, The University of Melbourne, Parkville, VIC 3010, Australia.
Insights
Pregnancy in aged, growth-restricted female rats revealed underlying cardiorenal and metabolic issues. Advanced maternal age negatively impacted fetal outcomes, regardless of maternal birth weight.
Area of Science:
- Reproductive biology
- Developmental origins of health and disease
- Cardiorenal and metabolic health
Background:
- Uteroplacental insufficiency links to adult cardiorenal and metabolic diseases.
- Being born small increases risks for gestational hypertension, diabetes, and delivering smaller babies.
- Advanced maternal age exacerbates pregnancy complications.
Purpose of the Study:
- To investigate if pregnancy in aged, growth-restricted female rats unmasks cardiorenal and metabolic dysfunction.
- To determine the impact on fetal growth.
Main Methods:
- Uteroplacental insufficiency induced via uterine vessel ligation in Wistar Kyoto rats.
- Growth-restricted F1 female offspring mated at 12 months with normal males.
- Pregnancy adaptations and F2 fetal outcomes assessed.
Main Results:
- Growth-restricted F1 females had elevated systolic blood pressure during pregnancy but normal renal/metabolic adaptations.
- F2 fetal weight was not significantly different between groups.
- Advanced maternal age reduced hypoglycemic response and decreased F2 fetal litter size and body weight in both groups.
Conclusions:
- Aged rats born small showed mostly normal pregnancy adaptations despite elevated blood pressure.
- Advanced maternal age, not low maternal birth weight, was associated with poorer fetal outcomes.
Abstract:
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.
