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Gender differences in the long-term effects of perinatal hypoxia on pulmonary circulation in rats

Václav Hampl,^1,2 Jana Bíbová,^1,2 Ivana Otádalová,^2,3 Viera Povilová,⁴ and Jan Herget^1,2

¹Departments of Physiology and ⁴Pathology, Charles University Second Medical School, 150 00 Prague 5; ³Institute of Physiology, Czech Academy of Sciences, and ²Centre for Experimental Cardiovascular Research, 142 20 Prague, Czech Republic

Submitted 15 November 2002 ; accepted in final form 9 April 2003

Some effects of perinatal hypoxia on pulmonary circulation are permanent. Since pulmonary vascular sensitivity to hypoxia in adults differs between sexes, we hypothesized that gender-based variability also exists in the long-term effects of perinatal hypoxia. Rats spent 1 wk before and 1 wk after birth in hypoxia (12% O₂) and then lived in normoxia. When adult, females, but not males, with the perinatal experience of hypoxia had right ventricle hypertrophy. To assess the role of sex hormones, some rats were gonadectomized in ether anesthesia as newborns. Compared with intact, perinatally normoxic controls, muscularization of peripheral pulmonary vessels in adulthood was augmented in perinatally hypoxic, neonatally gonadectomized males (by 85%) and much more so in females (by 533%). Pulmonary artery pressure was elevated in perinatally hypoxic, neonatally gonadectomized females (24.4 ± 1.7 mmHg) but not males (17.2 ± 0.6 mmHg). Gonadectomy in adulthood had no effect. We conclude that female pulmonary circulation is more sensitive to late effects of perinatal hypoxia, and these effects are blunted by the presence of ovaries during maturation.

sexual variability; ovaries; pulmonary hypertension; right ventricular hypertrophy; newborn

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