Chinese Journal of Child Health Care ›› 2023, Vol. 31 ›› Issue (2): 176-179.DOI: 10.11852/zgetbjzz2022-1140

• Review • Previous Articles     Next Articles

Research progress of hyperhomocysteinemia in inducing neural tube defects

SHEN Fu-hui, YIN Li-qin, WANG Fan   

  1. Department of Neonatalogy, Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China Corresponding author:WANG Fan,
  • Received:2022-09-14 Revised:2022-11-23 Online:2023-02-10 Published:2023-02-16
  • Contact: WANG Fan,


沈富辉, 尹立琴, 王凡   

  1. 兰州大学第二医院新生儿科,甘肃 兰州 730030
  • 通讯作者: 王凡,
  • 作者简介:沈富辉(1996-),男,甘肃人,住院医师,在读硕士研究生,主要研究方向为新生儿脑发育和脑损伤。
  • 基金资助:

Abstract: Neural tube defects (NTDs) are one of the most common central nervous system defects in newborns. Neural plate development, neural plate shape, neural plate curling, and nerve fold fusion are the four stages of neural tube closure, where genetic and environmental risk factors are involved. Through oxidative stress, Ca2+ overload, and a decreased S-adenosyl methionine(SAM)/S-adenosylhomocysteine(SAH) ratio, hyperhomocysteinemia(HHcy) causes overall DNA hypomethylation in the embryo, which results in high expression of genes involved in neural tube closure through histone modifications, gene polymorphisms, and methionine synthetase(MTR), as well as the activation of related signaling pathways(such as the Wnt/β-catenin signaling pathway and the PI3K/AKT signaling pathway), impairing the proper development of the neural tube, upsetting the equilibrium between cell proliferation and apoptosis, ultimately resulting in NTDs. Using data from earlier studies, this review strengthens the correlation between HHcy and NTDs, offers a theoretical framework for clinical NTD diagnosis and prevention, and goes into greater detail about the aforementioned pathways and their connection to HHcy.

Key words: neural tube defects, hyperhomocysteinemia, DNA methylation, oxidative stress

摘要: 神经管畸形(NTDs)是新生儿最常见的中枢神经系统缺陷之一,神经管闭合经过神经板形成、神经板塑形、神经板卷褶和神经褶融合四个阶段,此过程涉及遗传和环境两大危险因素。高同型半胱氨酸血症(HHcy)通过氧化应激、Ca2+超载、降低S-腺苷甲硫氨酸(SAM)/S-腺苷高半胱氨酸(SAH)比值等使胚胎整体DNA低甲基化,通过组蛋白修饰、基因多态性和甲硫氨酸合酶(MTR)等导致神经管闭合相关基因高表达,并激活相关信号通路(如Wnt/β-catenin信号通路和PI3K/AKT信号通路),破坏细胞增殖和凋亡之间的平衡,影响神经管正常发育,最终导致NTDs的发生。本文介绍HHcy与上述几种机制之间的关联,并进一步阐述HHcy对NTDs发生发展的影响,为临床上诊断和预防NTDs提供更为明确的理论依据。

关键词: 神经管畸形, 高同型半胱氨酸血症, DNA甲基化, 氧化应激

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