Sex-specific effects of advanced maternal age on cardiovascular function in aged adult rat offspring

Pregnancy at an advanced maternal age has an increased risk of complications for both the mothers and their offspring. We have previously shown that advanced maternal age in a rat model leads to poor fetal outcomes, maternal vascular dysfunction and hypertension, concordant with findings in humans. Moreover, offspring from aged dams had sex-specific cardiovascular dysfunction in young adulthood. Yet, the detrimental impact of aging on the cardiovascular system of the offspring in this model is unknown. We hypothesized that offspring born to aged dams (9.5-10 months old) would have impaired cardiovascular function at 12 months of age. Echocardiographic data revealed signs of mild left ventricular (LV) diastolic dysfunction in only male offspring from aged dams (Isovolumetric relaxation time (IVRT); young 34.27±2.04 vs. aged dam 27.61±0.99 msec; P<0.01 and E'/A'; young 1.08±0.04 vs. aged dam 0.96±0.02; P<0.05). In young adulthood (4 months of age), we previously showed that male, but not female, offspring born from aged dams had impaired recovery from ischemia/reperfusion (I/R) injury. Aging did not alter the susceptibility of female offspring to I/R injury. Interestingly, wire myography data revealed that male offspring from aged dams had enhanced vascular sensitivity to methacholine (MCh pEC50: young 7.4±0.08 vs. aged dam 7.9±0.11; P=0.007) due, in part, to increased prostaglandin-mediated vasodilation. Despite intact endothelium-dependent relaxation, female offspring from aged dams had elevated systolic blood pressure (young 125.3±4.2 mmHg vs. aged dam 144.0±6.9 mmHg, P=0.03). These data highlight sex-specific mechanisms underlying cardiovascular programming in offspring born to dams of advanced age.