Wang Sixing, Mei Zilin, Chen Jin, Zhao Kai, Kong Ruize, McClements Lana, Zhang Huiping, Liao Aihua, Liu Chunyan
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Second Clinical Department, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Clin Rev Allergy Immunol. 2025 Apr 2;68(1):36. doi: 10.1007/s12016-025-09049-y.
Congenital heart defects (CHD) are the most common major birth defects and one of the leading causes of death from congenital defects after birth. CHD can arise in pregnancy from the combination of genetic and non-genetic factors. The maternal immune activation (MIA) hypothesis is widely implicated in embryonic neurodevelopmental abnormalities. MIA has been found to be associated with the development of asthma, diabetes mellitus, and other diseases in the offspring. Given the important role of cardiac immune cells and cytokines in embryonic heart development, it is hypothesized that MIA may play a significant role in embryonic heart development. This review aims to stimulate further investigation into the relationship between MIA and CHD and to highlight the gaps in the knowledge. It evaluates the impact of MIA on CHD in the context of pregnancy complications, immune-related diseases, infections, and environmental and lifestyle factors. The review outlines the mechanisms by which immune cells and their secretome indirectly regulate the immuno-microenvironment of the embryonic heart by influencing placental development. Furthermore, the inflammatory cytokines cross the placenta to induce related reactions including oxidative stress in the embryonic heart directly. This review delineates the role of MIA in CHD and underscores the impact of maternal factors, especially immune factors, as well as the embryonic cardiac immuno-microenvironment, on embryonic heart development. This review extends our understanding of the importance of MIA in the pathogenesis of CHD and provides important insights into prenatal prevention and treatment strategies for this congenital condition.
先天性心脏病（CHD）是最常见的主要出生缺陷，也是出生后先天性缺陷导致死亡的主要原因之一。孕期CHD可能由遗传和非遗传因素共同作用引起。母体免疫激活（MIA）假说与胚胎神经发育异常密切相关。已发现MIA与后代哮喘、糖尿病及其他疾病的发生有关。鉴于心脏免疫细胞和细胞因子在胚胎心脏发育中的重要作用，推测MIA可能在胚胎心脏发育中起重要作用。本综述旨在激发对MIA与CHD之间关系的进一步研究，并突出知识空白。它在妊娠并发症、免疫相关疾病、感染以及环境和生活方式因素的背景下评估MIA对CHD的影响。综述概述了免疫细胞及其分泌组通过影响胎盘发育间接调节胚胎心脏免疫微环境的机制。此外，炎性细胞因子可穿过胎盘直接诱导胚胎心脏中的相关反应，包括氧化应激。本综述阐述了MIA在CHD中的作用，并强调了母体因素，尤其是免疫因素以及胚胎心脏免疫微环境对胚胎心脏发育的影响。本综述扩展了我们对MIA在CHD发病机制中的重要性的理解，并为这种先天性疾病的产前预防和治疗策略提供了重要见解。
