Preconception maternal hyperoxia exposure causes cardiac insufficiency through induction of mitochondrial toxicity in mice offspring

Although essential, excessive oxygen is toxic. The adverse effects of maternal hyperoxygenation have recently garnered attention. However, the potential toxicity of maternal hyperoxia exposure before pregnancy and its effects on offspring development remain unclear. This study aims to investigate the cardiac developmental toxicity of maternal pre-pregnancy hyperoxia exposure on the offspring. Our findings reveal that preconception maternal hyperoxia exposure leads to growth retardation, cardiac insufficiency, and remodeling in both male and female offspring. Additionally, maternal pre-pregnancy hyperoxia exposure induces mitochondrial damage characterized by reduced oxidative phosphorylation, inhibited tricarboxylic acid (TCA) cycle, and decreased ATP production in the cardiac tissues of offspring mice. Supplementation of sodium propionate during lactation significantly improves growth retardation, mitigates metabolic remodeling, and partially restores cardiac function in hyperoxia-exposed offspring. In conclusion, our study suggests that maternal hyperoxia exposure before pregnancy leads to cardiac insufficiency in murine offspring. These findings may have important implications for mitigating maternal high oxygen toxicity on offspring development and disease risk, especially the cardiotoxic effects of hyperoxia on offspring development.