Gestational Intermittent Hypoxia Programs Hypertensive Response in Female Rat Offspring: Impact of Ovaries

Obstructive sleep apnea (OSA) is a chronic condition frequently observed in pregnant women. We have shown that gestational intermittent hypoxia (GIH), a hallmark of OSA, leads to sex-specific impairment in the endothelium-dependent relaxation response and an increase in blood pressure in adult male but not female rat offspring. The present study tested the hypothesis that functional ovaries normalize GIH-induced hypertensive response in female offspring. Experiments were done in female offspring of pregnant rats exposed to normoxia or GIH (F_IO2 21-10.5% from gestational days 10 to 21). Ovariectomy and sham surgery were performed at 5 weeks of age. Pups born to GIH dams were significantly smaller than the controls, but they exhibited catch-up growth and were similar to controls by 5 weeks of age. Ovariectomy significantly exacerbated bodyweight gain to a similar extent in both control and GIH offspring. Marked increases in blood pressure were observed in pre-pubertal GIH offspring compared to controls; however, after puberty, blood pressure in GIH offspring progressively decreased and became normotensive at adulthood. Ovariectomy led to the maintenance of higher blood pressure in post-pubertal GIH offspring with no significant effect in controls. Vascular contractile and relaxation responses were not affected in the GIH and control offspring; however, ovariectomy selectively decreased endothelium-dependent relaxation response along with a decrease in endothelial nitric oxide synthase expression in the GIH offspring. These findings suggest that functional ovaries are crucial in protecting females against GIH-mediated endothelial dysfunction and hypertension in adulthood.