Abstract

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.