{"doi":"10.1101/2025.05.27.656260","title":"Maternal Vitamin C Deficiency and Genetic Risk Factors Contribute to Congenital Defects through Dysregulation of DNA Methylation","abstract":"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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558093,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1332538,"name":"Colin Custers","orcid":"0000-0001-6186-7909","position":1,"is_corresponding":false},{"id":1332813,"name":"Wannes Brangers","orcid":null,"position":2,"is_corresponding":false},{"id":1458080,"name":"Riet Cornelis","orcid":"0009-0002-6190-871X","position":3,"is_corresponding":false},{"id":1332536,"name":"Spyridon Champeris Tsaniras","orcid":"0000-0002-4960-9314","position":4,"is_corresponding":false},{"id":1458081,"name":"Kobe De Ridder","orcid":"0000-0001-7343-8642","position":5,"is_corresponding":false},{"id":1458082,"name":"Bernard Thienpont","orcid":"0000-0002-8772-6845","position":6,"is_corresponding":false},{"id":1336833,"name":"Huiyong Cheng","orcid":null,"position":7,"is_corresponding":false},{"id":259681,"name":"Qiuying Chen","orcid":"0000-0001-5909-3959","position":8,"is_corresponding":false},{"id":701292,"name":"Daniel C. Kraushaar","orcid":null,"position":9,"is_corresponding":false},{"id":371673,"name":"Richard H. Finnell","orcid":"0000-0002-5962-8754","position":10,"is_corresponding":false},{"id":259684,"name":"Steven S. Gross","orcid":"0000-0001-8029-2338","position":11,"is_corresponding":false},{"id":1332539,"name":"Kian Peng Koh","orcid":"0000-0003-2523-5175","position":12,"is_corresponding":false},{"id":1332534,"name":"Bernard K. van der Veer","orcid":"0000-0002-2576-7529","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-19T02:55:21.727661Z","pmid":"40502204","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}