Journal
JOURNAL OF PHYSIOLOGY-LONDON
Volume 596, Issue 23, Pages 5807-5821Publisher
WILEY
DOI: 10.1113/JP275472
Keywords
advanced maternal age; developmental programming; cardiovascular dysfunction
Categories
Funding
- Canadian Institutes of Health Research [CIHR: MOP 133675, FS 154313]
- Women and Children's Health Research Institute (WCHRI) through Stollery Children's Hospital Foundation (SCHF)
- and Children's Health Research Institute (WCHRI) through Royal Alexandra Hospital Foundation (RAHF)
- National Health and Medical Research Council of Australia [APP1092191]
- Heart and Stroke Foundation of Canada
- Alberta Innovates Health Solutions Canada [201200909]
- Molly Towell Foundation [RES0031751]
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Exposure to prenatal stressors, including hypoxia, micro- and macronutrient deficiency, and maternal stress, increases the risk of cardiovascular disease in adulthood. It is unclear whether being born from a mother of advanced maternal age (>= 35 years old) may also constitute a prenatal stress with cardiovascular consequences in adulthood. We previously demonstrated growth restriction in fetuses from a rat model of advanced maternal age, suggesting exposure to a compromised in utero environment. Thus, we hypothesized that male and female offspring from aged dams would exhibit impaired cardiovascular function as adults. In 4-month-old offspring, we observed impaired endothelium-dependent relaxation in male (P < 0.05) but not female offspring born from aged dams. The anti-oxidant polyethylene glycol superoxide dismutase improved relaxation only in arteries from male offspring of aged dams (Delta E-max: young dam -1.63 +/- 0.80 vs. aged dam 11.75 +/- 4.23, P < 0.05). Furthermore, endothelium-derived hyperpolarization-dependent relaxation was reduced in male but not female offspring of aged dams (P < 0.05). Interestingly, there was a significant increase in nitric oxide contribution to relaxation in females born from aged dams (Delta E-max: young dam -24.8 +/- 12.1 vs. aged dam -68.7 +/- 7.7, P < 0.05), which was not observed in males. Recovery of cardiac function following an ischaemia-reperfusion insult in male offspring born from aged dams was reduced by similar to 57% (P < 0.001), an effect that was not evident in female offspring. These data indicate that offspring born from aged dams have an altered cardiovascular risk profile that is sex-specific. Given the increasing trend toward delaying pregnancy, these findings may have significant population and health care implications and warrant further investigation.
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