{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:44:01Z","timestamp":1790613841900,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T00:00:00Z","timestamp":1640649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-156389"],"award-info":[{"award-number":["PJT-156389"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council","doi-asserted-by":"publisher","award":["RES 25104"],"award-info":[{"award-number":["RES 25104"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Folate and choline are interconnected metabolically. The MTHFD1 R653Q SNP is a risk factor for birth defects and there are concerns that choline deficiency may interact with this SNP and exacerbate health risks. 80\u201390% of women do not meet the Adequate Intake (AI) for choline. The objective of this study was to assess the effects of choline deficiency on maternal one-carbon metabolism and reproductive outcomes in the MTHFD1-synthetase deficient mouse (Mthfd1S), a model for MTHFD1 R653Q. Mthfd1S+\/+ and Mthfd1S+\/\u2212 females were fed control (CD) or choline-deficient diets (ChDD; 1\/3 the amount of choline) before mating and during pregnancy. Embryos were evaluated for delays and defects at 10.5 days gestation. Choline metabolites were measured in the maternal liver, and total folate measured in maternal plasma and liver. ChDD significantly decreased choline, betaine, phosphocholine, and dimethylglycine in maternal liver (p &lt; 0.05, ANOVA), and altered phosphatidylcholine metabolism. Maternal and embryonic genotype, and diet-genotype interactions had significant effects on defect incidence. Mild choline deficiency and Mthfd1S+\/\u2212 genotype alter maternal one-carbon metabolism and increase incidence of developmental defects. Further study is required to determine if low choline intakes contribute to developmental defects in humans, particularly in 653QQ women.<\/jats:p>","DOI":"10.3390\/nu14010127","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T02:31:27Z","timestamp":1640745087000},"page":"127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Mild Choline Deficiency and MTHFD1 Synthetase Deficiency Interact to Increase Incidence of Developmental Delays and Defects in Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1741-0375","authenticated-orcid":false,"given":"Karen E.","family":"Christensen","sequence":"first","affiliation":[{"name":"Departments of Human Genetics and Pediatrics, McGill University, Montreal, QC H3A 0C7, Canada"},{"name":"The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga V.","family":"Malysheva","sequence":"additional","affiliation":[{"name":"Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Carlin","sequence":"additional","affiliation":[{"name":"Division of Human Nutrition, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Matias","sequence":"additional","affiliation":[{"name":"Nutrition Research Division, Health Canada, Ottawa, ON K1A 0K9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"MacFarlane","sequence":"additional","affiliation":[{"name":"Nutrition Research Division, Health Canada, Ottawa, ON K1A 0K9, Canada"},{"name":"Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5525-1355","authenticated-orcid":false,"given":"Ren\u00e9 L.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Division of Human Nutrition, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7192-5743","authenticated-orcid":false,"given":"Marie A.","family":"Caudill","sequence":"additional","affiliation":[{"name":"Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Rozen","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics and Pediatrics, McGill University, Montreal, QC H3A 0C7, Canada"},{"name":"The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1636S","DOI":"10.3945\/jn.114.206599","article-title":"Biomarkers of nutrition for development\u2014Folate review","volume":"145","author":"Bailey","year":"2015","journal-title":"J. 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