High sucralose exposure in early pregnancy increases the susceptibility of heart defects in mice offspring

Maternal sucralose exposure during pregnancy has been demonstrated to interfere embryonic development, yet limited studies have investigated its potential hazards on fetal cardiogenesis. In the present study, we employed a mice model to investigate the impact of sucralose exposure in early pregnancy on the risk of heart defects in offspring. Pregnant C57BL/6J mice received either control or sucralose water. The incidence of heart defects in the sucralose group was 13.86%, significantly higher than that in the control group. Transcriptional downregulation of cardiogenic genes involving Gata4 , Nkx2.5 , Tbx5 , and Tbx20 were confirmed, potentially due to increased CREB phosphorylation. N-acetylcysteine (NAC) reduced CREB phosphorylation, partially reversed sucralose-induced suppression of cardiogenic genes, and reduced the incidence of heart defects from 16.67% to 4.81%. Our study demonstrates that sucralose exposure during early pregnancy increases the risk of heart defects via transcriptional suppression of cardiogenic genes, while NAC potentially functions as a protective factor.