Leung, Kit-Yi;
Weston, Eleanor;
De Castro, Sandra CP;
Nikolopoulou, Evanthia;
Sudiwala, Sonia;
Savery, Dawn;
Eaton, Simon;
... Greene, Nicholas DE; + view all
(2024)
Association of embryonic inositol status with susceptibility to neural tube defects, metabolite profile, and maternal inositol intake.
FASEB Journal
, 38
(11)
, Article e23738. 10.1096/fj.202400206R.
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Abstract
Maternal nutrition contributes to gene–environment interactions that influence susceptibility to common congenital anomalies such as neural tube defects (NTDs). Supplemental myo-inositol (MI) can prevent NTDs in some mouse models and shows potential for prevention of human NTDs. We investigated effects of maternal MI intake on embryonic MI status and metabolism in curly tail mice, which are genetically predisposed to NTDs that are inositol-responsive but folic acid resistant. Dietary MI deficiency caused diminished MI in maternal plasma and embryos, showing that de novo synthesis is insufficient to maintain MI levels in either adult or embryonic mice. Under normal maternal dietary conditions, curly tail embryos that developed cranial NTDs had significantly lower MI content than unaffected embryos, revealing an association between diminished MI status and failure of cranial neurulation. Expression of inositol-3-phosphate synthase 1, required for inositol biosynthesis, was less abundant in the cranial neural tube than at other axial levels. Supplemental MI or d-chiro-inositol (DCI) have previously been found to prevent NTDs in curly tail embryos. Here, we investigated the metabolic effects of MI and DCI treatments by mass spectrometry-based metabolome analysis. Among inositol-responsive metabolites, we noted a disproportionate effect on nucleotides, especially purines. We also found altered proportions of 5-methyltetrahydrolate and tetrahydrofolate in MI-treated embryos suggesting altered folate metabolism. Treatment with nucleotides or the one-carbon donor formate has also been found to prevent NTDs in curly tail embryos. Together, these findings suggest that the protective effect of inositol may be mediated through the enhanced supply of nucleotides during neural tube closure.
| Type: | Article |
|---|---|
| Title: | Association of embryonic inositol status with susceptibility to neural tube defects, metabolite profile, and maternal inositol intake |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1096/fj.202400206R |
| Publisher version: | https://doi.org/10.1096/fj.202400206r |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biology, Cell Biology, Life Sciences & Biomedicine - Other Topics, inositol, mass spectrometry, metabolome, mice, neural tube defects, nucleotides, D-CHIRO-INOSITOL, FOLIC-ACID, SPINA-BIFIDA, CURLY-TAIL, FOLATE, MYOINOSITOL, PREVENTION, RISK, SUPPLEMENTATION, HYPERGLYCEMIA |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10207456 |
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