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

Autor:	Cai K; Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Rd, Shanghai 200092, China., Wang F; NHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, and School of Life Sciences, Fudan University, 399 Wanyuan Rd, Shanghai 200438, China., Shi HQ; Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Rd, Shanghai 200092, China.; NHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, and School of Life Sciences, Fudan University, 399 Wanyuan Rd, Shanghai 200438, China., Shen AN; NHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, and School of Life Sciences, Fudan University, 399 Wanyuan Rd, Shanghai 200438, China., Zhao R; Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Rd, Shanghai 200092, China., Geng HR; NHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, and School of Life Sciences, Fudan University, 399 Wanyuan Rd, Shanghai 200438, China., Lu JQ; NHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, and School of Life Sciences, Fudan University, 399 Wanyuan Rd, Shanghai 200438, China., Gui YH; NHC Key Laboratory of Neonatal Diseases, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, and School of Life Sciences, Fudan University, 399 Wanyuan Rd, Shanghai 200438, China., Shi Y; Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Rd, Shanghai 200092, China., Zhao JY; Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Rd, Shanghai 200092, China.
Jazyk:	angličtina
Zdroj:	Cardiovascular research [Cardiovasc Res] 2024 Dec 14; Vol. 120 (16), pp. 2092-2103.
DOI:	10.1093/cvr/cvae203
Abstrakt:	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 in cardiac function were inhibited at the transcriptional level possibly due to increased DNA methylation. Among these, superoxide dismutase 1 was down-regulated, and reactive oxygen species (ROS) levels increased in the mouse heart. Inhibition of ROS generation using the antioxidant N-acetylcysteine rescued the impaired cardiac function resulting from maternal FA over-supplementation. Conclusions: Our study revealed that over-supplementation with FA during mouse pregnancy is detrimental to cardiac function with the decreased left ventricular ejection fraction in the offspring and provides insights into the mechanisms underlying the association between maternal FA status and health outcomes in the offspring. Competing Interests: Conflict of interest: none declared. (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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