{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:35:07Z","timestamp":1760060107611,"version":"build-2065373602"},"reference-count":62,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"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-173521"],"award-info":[{"award-number":["PJT-173521"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Low folate intake before and during pregnancy increases the risk of neural tube defects and other adverse outcomes. Gene variants such as MTHFR 677C&gt;T (rs1801133) may increase risks associated with suboptimal folate intake. Our objective was to use BALB\/cJ Mthfr677C&gt;T mice to evaluate the effects of the TT genotype and low folate diets on embryonic development and MTHFR protein expression in pregnant mice. Methods: Female 677CC (mCC) and 677TT (mTT) mice were fed control (2 mg folic acid\/kg (2D)), 1 mg folic acid\/kg (1D) and 0.3 mg folic acid\/kg (0.3D) diets before and during pregnancy. Embryos and maternal tissues were collected at embryonic day 10.5. Embryos were examined for developmental delays and defects. Methyltetrahydrofolate (methylTHF) and total homocysteine (tHcy) were measured in maternal plasma, and MTHFR protein expression was evaluated in maternal liver. Results: MethylTHF decreased due to the experimental diets and mTT genotype. tHcy increased due to 0.3D and mTT genotype; mTT 0.3D mice had significantly higher tHcy than the other groups. MTHFR expression was lower in mTT liver than mCC. MTHFR protein expression increased due to low folate diets in mCC mice, whereas in mTT mice, MTHFR expression increased only due to 1D. Developmental delays were increased in the litters of mTT mice fed 1D and 0.3D. Conclusions: The Mthfr677C&gt;T mouse models the effects of the MTHFR 677TT genotype in humans and provides a folate-responsive model for examination of the effects of folate intake and the MTHFR 677C&gt;T variant during gestation.<\/jats:p>","DOI":"10.3390\/nu17152536","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T11:54:51Z","timestamp":1754308491000},"page":"2536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low Dietary Folate Increases Developmental Delays in the Litters of Mthfr677TT Mice"],"prefix":"10.3390","volume":"17","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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7179-933X","authenticated-orcid":false,"given":"Marie-Lou","family":"Faquette","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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vafa","family":"Keser","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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alaina M.","family":"Reagan","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron T.","family":"Gebert","sequence":"additional","affiliation":[{"name":"Center of Metabolomics, Institute of Metabolic Disease, Baylor Scott and White Research Institute, Dallas, TX 75204, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4199-7551","authenticated-orcid":false,"given":"Teodoro","family":"Bottiglieri","sequence":"additional","affiliation":[{"name":"Center of Metabolomics, Institute of Metabolic Disease, Baylor Scott and White Research Institute, Dallas, TX 75204, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0565-6474","authenticated-orcid":false,"given":"Gareth R.","family":"Howell","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,1]]},"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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