Article ID: 24-427
Congenital heart defects (CHD) are internal risk factors that cause cardiac dysfunction. Maternal smoking is a cause of inducing CHD and cardiac dysfunction. Here, we aimed to investigate the influence of nicotine on fetal cardiac dysfunction and the underlying mechanism in mice. After maternal nicotine exposure (MNE), the female mice became pregnant, and the successful pregnancy rate was calculated. Fetal weight, cardiac function, and placental weight were measured at embryonic day 18.5. For in vitro experiments, primary cardiomyocytes were isolated. Cell apoptosis and inflammation were analyzed using flow cytometry and enzyme-linked immunosorbent assay. The molecular mechanism was evaluated using molecular docking, quantitative real-time PCR, and western blotting. The results showed that MNE reduced the fetal weight, cardiac function, and maternal pregnancy rate in vivo. Nicotine promotes apoptosis and inflammation of cardiomyocytes in vitro. Moreover, nicotine decreased KCTD10 expression and activated the Notch pathway. Inactivation of the Notch pathway using DAPT reversed the effects of nicotine on cardiomyocyte injury and MNE on fetal cardiac dysfunction. In conclusion, nicotine may promote fetal cardiac dysfunction by facilitating cardiomyocyte apoptosis through the KCTD10-Notch pathway.
