Sex differences and the effects of intrauterine hypoxia on growth and in vivo heart function of fetal guinea pigs.

We hypothesized that the physiological adaptations of the fetus in response to chronic intrauterine hypoxia depend on its sex and the gestational age of exposure. METHODS Pregnant guinea pigs were exposed to room air (normoxia, NMX) or 10.5%O2 (hypoxia, HPX) at either 25d (Early Onset) or 50d (Late Onset) gestation until term (~65d). We evaluated the effects of hypoxia on hemodynamic and cardiac function indices using Doppler ultrasound (US) and determined sex-related differences in near-term fetuses. Indices of uterine/umbilical artery pulsatility (PI index) and fetal heart systolic and diastolic function (Tei index and E/A ratios, respectively) were measured in utero and fetal body (FBW) and organ weights measured from extracted fetuses. RESULTS Both early and late onset HPX decreased FBW in both males and females, had no effect on placenta wts, and increased placenta wt/FBW ratios. Early but not late onset HPX increased uterine artery PI but neither HPX condition affected umbilical artery PI. Early onset HPX increased left ventricle E/A ratios in both males and females while late onset HPX increased right ventricle E/A ratio in females only. Hypoxia had no effect on the Tie index in either sex. CONCLUSIONS Early and late onset HPX induce placental insufficiency, fetal growth restriction, and increase diastolic filling depending on the sex, with female fetuses having a greater capacity than males to compensate to intrauterine hypoxia.