Maternal folic acid over-supplementation impairs cardiac function in mice offspring by inhibiting SOD1 expression

作者：Ke Cai, Feng Wang, Hai-Qun Shi, Anna Shen, Rui Zhao, Hao‐Ran Geng, Jia-Quan Lu, Yonghao Gui, Yan Shi, Jian‐Yuan Zhao · 发表于：Cardiovascular Research · 年份：2024 · DOI：10.1093/cvr/cvae203 · 被引用次数：11 · 研究领域：Folate and B Vitamins Research、Birth, Development, and Health、Health, Environment, Cognitive Aging

AIMS: Folic acid (FA) supplementation during pregnancy aims to protect foetal development. However, maternal over-supplementation of FA has been demonstrated to cause metabolic dysfunction and increase the risk of autism, retinoblastoma, and respiratory illness in the offspring. Moreover, FA supplementation reduces the risk of congenital heart disease. However, little is known about its possible adverse effects on cardiac health resulting from maternal over-supplementation. In this study, we assessed the detrimental effects of maternal FA over-supplementation on the cardiac health of the offspring. METHODS AND RESULTS: Eight-week-old C57BL/6J pregnant mice were randomly divided into control and over-supplemented groups. The offspring cardiac function was assessed using echocardiography. Cardiac fibrosis was assessed in the left ventricular myocardium by histological analysis. Proteomic, protein, RNA, and DNA methylation analyses were performed by liquid chromatography-tandem mass spectrometry, western blotting, real-time quantitative PCR, and bisulfite sequencing, respectively. We found that maternal periconceptional FA over-supplementation impaired cardiac function with the decreased left ventricular ejection fraction in the offspring. Biochemical indices and tissue staining further confirmed impaired cardiac function in offspring caused by maternal FA over-supplementation. The combined proteomic, RNA expression, and DNA methylation analyses suggested that key genes involved...