Language
English
Publication Date
5-30-2025
Journal
bioRxiv
DOI
10.1101/2025.05.27.656260
PMID
40502204
PMCID
PMC12154938
PubMedCentral® Posted Date
5-30-2025
PubMedCentral® Full Text Version
Pre-Print
Abstract
Maternal dietary insufficiencies can reshape the fetal epigenome during gestation, contributing to birth defects and developmental disorders. Vitamin C (VitC) is a critical co-factor for Ten-Eleven-Translocation (TET) DNA demethylases, but the impact of its deficiency on embryonic development has gone largely unappreciated. Here, we show that maternal VitC deficiency in L-gulonolactone oxidase (Gulo)-deficient mice, which like humans are unable to synthesize VitC, can cause highly penetrant developmental delays and malformations in non-inbred embryos during the vulnerable period of gastrulation. DNA hypermethylation in Gulo−/− embryonic neural tissues of susceptible strains increases with VitC dose reduction and with the severity of embryonic pathologies, coinciding with hallmarks of TET1 dysfunction. A moderate reduction in VitC status is sufficient to induce DNA hypermethylation and cause neural tube defects. Our results suggest that promoting timely VitC supplementation by at-risk pregnant mothers may prevent a range of birth defects and enhance health outcomes of future generations.
Published Open-Access
yes
Recommended Citation
van der Veer, Bernard K; Custers, Colin; Brangers, Wannes; et al., "Maternal Vitamin C Deficiency and Genetic Risk Factors Contribute to Congenital Defects through Dysregulation of DNA Methylation" (2025). Faculty, Staff and Students Publications. 8565.
https://digitalcommons.library.tmc.edu/baylor_docs/8565