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Protective effect of antioxidants on cardiac function in adult offspring exposed to prenatal overnutrition

Published online by Cambridge University Press:  11 March 2022

Jialing Zhang Open the ORCID record for Jialing Zhang [Opens in a new window] ,
Li Cao ,
Wenji Wang ,
Yu Huo ,
Yuanzheng Zheng ,
Fang Wu  and
Yonghao Gui Open the ORCID record for Yonghao Gui [Opens in a new window]
Jialing Zhang
Affiliation:
Institute of Pediatrics, Children’s Hospital of Fudan University, Shanghai, China NHC Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China
Li Cao
Affiliation:
Ultrasound Department, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
Wenji Wang
Affiliation:
Institute of Pediatrics, Children’s Hospital of Fudan University, Shanghai, China NHC Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China
Yu Huo
Affiliation:
NHC Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China Cardiovascular Center, Children’s Hospital of Fudan University, Shanghai, China
Yuanzheng Zheng
Affiliation:
NHC Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China Cardiovascular Center, Children’s Hospital of Fudan University, Shanghai, China
Fang Wu
Affiliation:
Department of Neonatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yonghao Gui*
Affiliation:
NHC Key Laboratory of Neonatal Diseases, Fudan University, Shanghai, China Cardiovascular Center, Children’s Hospital of Fudan University, Shanghai, China
*
Address for correspondence: Yonghao Gui, NHC Key Laboratory of Neonatal Diseases, Fudan University, 399 Wanyuan Road, Minhang District, Shanghai 201102, China. Email: [email protected]
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Abstract

Maternal overnutrition-induced fetal programming predisposes offspring to cardiovascular health issues throughout life. Understanding how these adverse cardiovascular effects are regulated at the maternal–fetal crosstalk will provide insight into the mechanisms of these cardiovascular diseases, which will help in further identifying potential targets for intervention. Here, we uncover a role of oxidative stress caused by prenatal overnutrition in governing cardiac damage. Mice exposed to maternal obesity showed remarkable pathological cardiomyocyte hypertrophy (p male < 0.001, Cohen’s d male = 1.77; p female < 0.001, Cohen’s d female = 1.94), increased collagen content (p male < 0.001, Cohen’s d male = 2.13; p female < 0.001, Cohen’s d female = 2.71), and increased levels of transforming growth factor β (TGF-β) (p male < 0.001, Cohen’s d male = 3.02; p female < 0.001, Cohen’s d female = 4.52), as well as left ventricular dysfunction in adulthood. To cope with increased oxidative stress in the myocardial tissue of offspring from obese mothers, we sought to decrease the effect of oxidative stress and prevent the development of these cardiovascular conditions with use of the antioxidant N-acetylcysteine during pregnancy. As predicted, after treatment with the antioxidant, there was greatly mitigated cardiomyocyte hypertrophy (p male < 0.001, Cohen’s d male = 1.31; p female < 0.001, Cohen’s d female = 0.82) and cardiac fibrosis, including decreased composition of collagen fibers (p male < 0.01, Cohen’s d male = 1.45; p female < 0.05, Cohen’s d female = 1.23) and reduced levels of TGF-β (p male < 0.05, Cohen’s d male = 1.83; p female < 0.01, Cohen’s d female = 3.81). We also observed improved left ventricle contractile function together with the alleviation of enhanced oxidative stress in the myocardial tissue of offspring. Collectively, these results established a crucial role of oxidative stress in prenatal overnutrition-associated ventricular remodeling and cardiac dysfunction. Our findings provided an important target for intervention of cardiovascular disease in overnutrition-related fetal programming.

Keywords

Oxidative stressprenatal overnutritionantioxidantsventricular remodelingcardiac dysfunction
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 13 , Issue 6 , December 2022 , pp. 741 - 749
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Copyright
© The Author(s), 2022. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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Footnotes

Jialing Zhang and Li Cao are contributed equally to this work.

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