{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:45:24Z","timestamp":1761489924952},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,2,22]],"date-time":"2016-02-22T00:00:00Z","timestamp":1456099200000},"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":[[2016,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Periconceptional supplementation with folic acid results in a significant reduction in the incidence of neural tube defects (NTDs). Nonetheless, NTDs remain a leading cause of perinatal morbidity and mortality worldwide, and the mechanism(s) by which folate exerts its protective effects are unknown. Homocysteine is an amino acid that accumulates under conditions of folate\u2010deficiency, and is suggested as a risk factor for NTDs. One proposed mechanism of homocysteine toxicity is its accumulation into proteins in a process termed homocysteinylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods &amp; Results<\/jats:title><jats:p>Herein, we used a folate\u2010deficient diet in pregnant mice to demonstrate that there is: (i) a significant inverse correlation between maternal serum folate levels and serum homocysteine; (ii) a significant positive correlation between serum homocysteine levels and titers of autoantibodies against homocysteinylated protein; and (iii) a significant increase in congenital malformations and NTDs in mice deficient in serum folate. Furthermore, in mice administered the folate\u2010deplete diet before conception, supplementation with folic acid during the gestational period completely rescued the embryos from congenital defects, and resulted in homocysteinylated protein titers at term that are comparable to that of mice administered a folate\u2010replete diet throughout both the pre\u2010 and postconception period. These results demonstrate that a low\u2010folate diet that induces NTDs also increases protein homocysteinylation and the subsequent generation of autoantibodies against homocysteinylated proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data support the hypotheses that homocysteinylation results in neo\u2010self antigen formation under conditions of maternal folate deficiency, and that this process is reversible with folic acid supplementation. Birth Defects Research (Part A) 106:201\u2013207, 2016. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23483","type":"journal-article","created":{"date-parts":[[2016,2,22]],"date-time":"2016-02-22T11:08:52Z","timestamp":1456139332000},"page":"201-207","source":"Crossref","is-referenced-by-count":18,"title":["Autoantibodies against homocysteinylated protein in a mouse model of folate deficiency\u2010induced neural tube defects"],"prefix":"10.1002","volume":"106","author":[{"given":"Kerina J.","family":"Denny","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences University of Queensland Brisbane Australia"},{"name":"School of Medicine University of Queensland Brisbane Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina F.","family":"Kelly","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences University of Queensland Brisbane 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