{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:10:37Z","timestamp":1791011437058,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,2,12]],"date-time":"2009-02-12T00:00:00Z","timestamp":1234396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold>Despite extensive research on mild methylenetetrahydrofolate reductase (MTHFR) deficiency and low dietary folate in different disorders, the association of these metabolic disturbances with a variety of congenital defects and pregnancy complications remains controversial. In this study we investigated the effects of MTHFR and dietary folate deficiency at 10.5 days post coitum (dpc) in our mouse model of mild MTHFR deficiency.<jats:bold>METHODS:<\/jats:bold><jats:italic>Mthfr<\/jats:italic>+\/+ and +\/\u2212 female mice were fed a control or folic acid\u2013deficient diet for 6 weeks, then mated with<jats:italic>Mthfr<\/jats:italic>+\/\u2212 males. At 10.5 dpc, embryos were examined and placentae were collected for histologic evaluation.<jats:bold>RESULTS:<\/jats:bold>Maternal MTHFR and folate deficiencies resulted in increased developmental delays and smaller embryos. We also observed a low frequency of a variety of embryonic defects in the experimental groups, such as neural tube, heart looping, and turning defects; these results mimic the low incidence and multifactorial nature of these anomalies in humans. Folate\u2010deficient mice also had increased embryonic losses and severe placental defects, including placental abruption and disturbed patterning of placental layers. Folate\u2010deficient placentae had decreased ApoA\u2010I expression, and there was a trend toward a negative correlation between ApoA\u2010I expression with maternal homocysteine concentrations.<jats:bold>CONCLUSIONS:<\/jats:bold>Our study provides biological evidence linking maternal MTHFR and dietary folate deficiencies to adverse pregnancy outcomes in mice. It underscores the importance of folate not only in reducing the incidence of early embryonic defects, but also in the prevention of developmental delays and placental abnormalities that may increase susceptibility to other defects and to reproductive complications. Birth Defects Research (Part A), 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdra.20575","type":"journal-article","created":{"date-parts":[[2009,2,12]],"date-time":"2009-02-12T22:37:29Z","timestamp":1234478249000},"page":"531-541","source":"Crossref","is-referenced-by-count":62,"title":["Methylenetetrahydrofolate reductase deficiency and low dietary folate increase embryonic delay and placental abnormalities in mice"],"prefix":"10.1002","volume":"85","author":[{"given":"Laura","family":"Pickell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deqiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie 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