Med Hypotheses
Department of Organ & Tissue Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashiku, Hamamatsu, Shizuoka 431-3192, Japan. Electronic address:
Published: January 2020
Neural tube defects (NTDs) originate from a failure of the embryonic neural tube to close. The pathogenesis of NTDs is largely unknown. Fortunately, adequate maternal folate application is known to reduce the risk of human NTDs. However, why folate reduces NTDs is largely unknown. The main cause for NTDs is the disturbance of the cell growth in the neuroepithelium. Of course, rapid cell growth needs enough synthesis of nuclei acids. Interestingly, folate is used as a source for the synthesis of nucleic acids. Furthermore, glycine cleavage system (GCS) is essential for the synthesis of nucleic acids from folate, and very strongly expressed in neuroepithelial cells, suggesting that these highly proliferating cells need enough synthesis of nuclei acids and high amounts of folate. Taken together, I speculate the following hypothesis; (1) The closure of the neural tube requires rapid growth of neuroepithelial cells. (2) High rates of nuclei acids synthesis are needed for the rapid growth. (3) GCS, which is requisite in nucleic acid synthesis from folate, is expressed very strongly and functions robustly in neuroepithelial cells. (4) Pregnant women require 5-10-fold higher amounts of folate compared to non-pregnant women. (5) So, folate-deficient situations are easy to occur in neuroepithelial cells, resulting in NTDs. (6) Thus, folate is effective to prevent NTDs.
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http://dx.doi.org/10.1016/j.mehy.2019.109429 | DOI Listing |
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Department of Occupational Safety and Health, College of Public Health, China Medical University, No. 100, Section 1, Economic and Trade Road, Beitun District, Taichung, 406040, Taiwan, Republic of China.
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The Francis Crick Institute, 1 Midland Rd, London, NW1 1AT, UK.
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Clinical Sciences, California Northstate University College of Medicine, Elk Grove, CA, USA.
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Department of Global Health, Faculty of Health Sciences, McMaster University, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada.
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2nd Department of Gynecology and Obstetrics, University Hospital Bratislava and Comenius University, 821 01 Bratislava, Slovakia.
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