Impact of Maternal Exercise on Mice Offspring Development, Pulmonary Hypertension, and Vascular Remodeling in Chronic Hypoxia

Abstract

ABSTRACT Purpose Chronic, high-altitude hypoxic exposure increases the risk of high-altitude pulmonary hypertension (PH). Emerging evidence shows maternal exercise may improve offspring resistance to disease throughout life. The purpose of this study is to determine if maternal exercise mitigates chronic hypoxic-induced changes in the offspring indicative of high-altitude PH development. Methods Female adult C57BL/6J mice were randomly allocated to nonexercise or exercise conditions. Exercise consisted of voluntary running wheel exercise for 4 wk during the perinatal period. Three days after birth, the pups remained at low altitude (normoxia) or were exposed to hypobaric hypoxia of 450 mm Hg to simulate ~4500 m of altitude exposure until 8 wk of age. The study consisted of four groups: hypoxia + nonexercise pregnancy, hypoxia + exercise, or the respective normoxia conditions (normoxia + nonexercise or normoxia + exercise). Offspring body size, motor function, right ventricular systolic pressure (RVSP), and cardiopulmonary morphology were assessed after 8 wk in normoxia or hypoxia. Results Both hypoxic groups had smaller body sizes, reduced motor function, increased hematocrit, RVSP, muscularization in medium-sized pulmonary arteries, as well as right ventricular hypertrophy and contractility compared with the normoxic groups (P < 0.05). Conclusions Chronic hypoxia simulating 4500 m attenuated growth, lowered motor function, and elicited PH development. Voluntary maternal exercise did not significantly decrease RVSP in the offspring, which aligned with a lack of effect to attenuate abnormal body size and cardiopulmonary development due to chronic hypoxia. These findings are preliminary in nature, and more powered studies through larger group sizes are required to generalize the results to the population.