Gestational intermittent hypoxia induces sex-specific impairment in endothelial mechanisms and sex-steroid hormone levels in rat male offspring

Obstructive sleep apnea (OSA) is a highly prevalent disorder during pregnancy and is associated with adverse fetal outcomes. We examined whether gestational intermittent hypoxia (GIH), the main feature of OSA, leads to alteration in blood pressure in the offspring and if this is related to sex-specific changes in vascular mechanisms. Pregnant rats were exposed to intermittent hypoxia from gestation day 10 to 21. Similarly handled animals exposed to intermittent ambient air served as controls. GIH exposure did not significantly alter food and water intake in dams. The male and female pups born to GIH dams were smaller in weight by 14% and 12%, respectively, compared with controls, and exhibited catch-up growth. Cardiac function was not affected in either GIH males or females. Blood pressure at 12 weeks of age was elevated in GIH males, but not females, compared with controls. While mesenteric arterial contractile responses to phenylephrine and endothelin were unaffected in GIH males and females, arterial relaxation to acetylcholine was reduced in GIH males but not females. Relaxation to sodium-nitroprusside was unaffected in both GIH males and females. Vascular eNOS expression was not changed, but phospho(Ser 1177 )-eNOS was decreased in GIH males. eNOS and its phosphorylation were unaffected in GIH females. Serum testosterone and estradiol levels were higher in GIH males but were unaltered in GIH females. Together, these findings suggest that GIH leads to a sex-specific increase in blood pressure in adult male offspring with blunted endothelial relaxation mechanisms, decreases in eNOS activity and elevated testosterone and estradiol levels.