Sex-Specific Effects of Prenatal Hypoxia and a Placental Antioxidant Treatment on Cardiac Mitochondrial Function in the Young Adult Offspring

Prenatal hypoxia is associated with placental oxidative stress, leading to impaired fetal growth and an increased risk of cardiovascular disease in the adult offspring; however, the mechanisms are unknown. Alterations in mitochondrial function may result in impaired cardiac function in offspring. In this study, we hypothesized that cardiac mitochondrial function is impaired in adult offspring exposed to intrauterine hypoxia, which can be prevented by placental treatment with a nanoparticle-encapsulated mitochondrial antioxidant (nMitoQ). Cardiac mitochondrial respiration was assessed in 4-month-old rat offspring exposed to prenatal hypoxia (11% O2) from gestational day (GD)15-21 receiving either saline or nMitoQ on GD 15. Prenatal hypoxia did not alter cardiac mitochondrial oxidative phosphorylation capacity in the male offspring. In females, the NADH + succinate pathway capacity decreased by prenatal hypoxia and tended to be increased by nMitoQ. Prenatal hypoxia also decreased the succinate pathway capacity in females. nMitoQ treatment increased respiratory coupling efficiency in prenatal hypoxia-exposed female offspring. In conclusion, prenatal hypoxia impaired cardiac mitochondrial function in adult female offspring only, which was improved with prenatal nMitoQ treatment. Therefore, treatment strategies targeting placental oxidative stress in prenatal hypoxia may reduce the risk of cardiovascular disease in adult offspring by improving cardiac mitochondrial function in a sex-specific manner.

Automated summary

Prenatal hypoxia impairs cardiac mitochondrial function in adult female offspring, but this can be improved with prenatal treatment using a nanoparticle-encapsulated mitochondrial antioxidant. The study found that prenatal hypoxia did not affect cardiac mitochondrial function in male offspring, while it decreased the capacity of certain mitochondrial pathways in females. However, treatment with nMitoQ increased respiratory coupling efficiency in female offspring exposed to prenatal hypoxia. This suggests that targeting placental oxidative stress in prenatal hypoxia may reduce the risk of cardiovascular disease in adult offspring by improving cardiac mitochondrial function, specifically in females.