1. Higher serum homocysteine and lower thyroid hormone levels in pregnant women are associated with neural tube defects.
- Author
-
Gu, Yan-Hong, Zhang, Qin, Guo, Jin, Wang, Fang, Bao, YiHua, Qiu, ZhiYong, Zheng, Ping, Ushijima, Masaru, Matsuura, Masaaki, Xie, XiangHui, and Zhang, Ting
- Subjects
NEURAL tube defects ,PREGNANT women ,THYROID hormones ,THYROID hormone regulation ,HOMOCYSTEINE ,NEURAL stem cells ,FETUS - Abstract
• We explored multiple coexisting factors associated with NTDs. • High tHcy coexisting with inadequate free T4 was 3 times more at risk of NTDs. • High Hcy might affect metabolism of thyroid hormones through modifying genes. This study tested the hypothesis that abnormal maternal metabolism of both homocysteine and thyroid hormone network in pregnant women is associated with neural tube defects (NTDs) in a part of China with high NTD prevalence. A case–control study was performed between 2007 and 2009 in Lüliang Mountains, Shanxi Province. This study included 83 pregnant women who had fetuses with NTDs (cases) and 90 pregnant women with normal fetuses (controls). In addition, a cell model to illustrate the epidemiological findings was established. Fetuses of mother who had both high total homocysteine (tHcy) and inadequate free thyroxine were 3 times more at risk of developing NTDs (adjusted odds ratio = 3.5; 95 % confidence interval = 1.2–10.4; cases vs. controls) using multivariate logistic regression models. Furthermore, biological interaction between metabolisms of Hcy and thyroid hormones was demonstrated in vitro. In homocysteine thiolactone of a metabolite of Hcy-treated mouse embryonic neural stem NE4C cells, genes (Bmp7, Ctnnb1, Notch 1, Gli2, and Rxra) related to both neural tube closure and thyroid hormone network were shown to be regulated by H3K79 homocysteinylation, which increased their expression levels. The effect of maternal serum high tHcy on risk of developing NTDs is depended on maternal serum level of thyroxine. Meanwhile, a higher level of tHcy might also affect both maternal metabolism of thyroid hormone and neural tube closure in embryogenesis through homocysteinylation of histones. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF