Higher serum homocysteine and lower thyroid hormone levels in pregnant women are associated with neural tube defects |
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| Affiliation: | 1. Department of Hygiene and Public Health, Osaka Medical and Pharmaceutical University, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan;2. Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China;3. Beijing FangShan District Maternal and Child Health Care Hospital, Beijing 102488, China;4. Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan;5. Teikyo Graduate School of Public Health, Tokyo 173-8605, Japan;1. Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Chemistry Department, CReAA, via Bologna 148, Turin, Italy;2. ASL BI Local Veterinary Service Veterinary Biella, BI, Italy;1. Saint-Petersburg Research Institute of Ear, Throat, Nose and Speech, St. Petersburg, Russia;2. I.I. Mechnikov North-Western State Medical University, St. Petersburg, Russia;3. K.A. Raukhfus Children''s City Multidisciplinary Clinical Center for High Medical Technologies, St. Petersburg, Russia;4. First Pavlov State Medical University of Saint Petersburg, St. Petersburg, Russia;5. National Center of Morphological Diagnostic, St. Petersburg, Russia;6. Institute of General Pathology and Pathophysiology, Moscow, Russia;7. I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;8. K.G. Razumovsky Moscow State University of Technologies and Management, Moscow, Russia;9. Yaroslavl State University, Yaroslavl, Russia;1. Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Fukui, Fukui, 910-1193, Japan;2. Department of Nursing, Faculty of Nursing and Welfare Sciences, Fukui Prefectural University, Fukui, 910-1195, Japan;1. Research Laboratory Education, Motricité, Sport et Santé, EM2S, LR19JS01, High Institute of Sport and Physical Education of Sfax, University of Sfax, 3000, Tunisia;2. Laboratory of Biochemistry, CHU Habib Bourguiba, University of Sfax, 3000, Tunisia;1. Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Para, Belém, PA, Brazil;2. Laboratory of Molecular Pharmacology, Institute of Biological Sciences, Federal University of Para, Belém, PA, Brazil;1. Departmento de Dentística, Endodontia e Materiais Odontológicos, Faculdade de Odontologia de Bauru, FOB/USP, Bauru, Brazil;2. Departmento de Cirurgia e Clínica Integrada, Faculdade de Odontologia de Araçatuba, FOA/UNESP, Araçatuba, Brazil;3. Departmento de Odontologia Restauradora, Faculdade de Odontologia de Araçatuba, FOA/UNESP, Araçatuba, Brazil;4. Departmento de Endodontia, Faculdade de Odontologia da Universidade Federal do Ceará – Campus de Sobral, UFC, Sobral, Brazil;5. School of Medicine and Dentistry Griffith University, Queensland, Australia |
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| Abstract: | BackgroundThis 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.MethodsA 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.ResultsFetuses 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.ConclusionsThe 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. |
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| Keywords: | Neural tube defect Recurrence Homocysteine Thyroid hormone Micronutrient Pregnancy |
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