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The developmental origin of health and disease highlights the importance of the period of the first 1000 days (from conception to 2 years) of life. This study aimed to evaluate the effect of early life stage folic acid deficiency on de novo telomere synthesis, neurobehavioral development, and the cognitive function of offspring rats. The rats were divided into three diet treatment groups: folate-deficient, folate-normal, and folate-supplemented. They were fed the corresponding diet from 5 weeks of age to the end of the lactation period. After weaning, the offspring rats were still fed with the corresponding diet for up to 100 days. Neurobehavioral tests, folic acid and homocysteine (Hcy) levels, relative telomere length in brain tissue, and uracil incorporation in telomere in offspring were measured at different time points. The results showed that folic acid deficiency decreased the level of folic acid, increased the level of Hcy of brain tissue in offspring, increased the wrong incorporation of uracil into telomeres, and hindered de novo telomere synthesis. However, folic acid supplementation increased the level of folic acid, reduced the level of Hcy of brain tissue in offspring, reduced the wrong incorporation of uracil into telomeres, and protected de novo telomere synthesis of offspring, which was beneficial to the development of early sensory-motor function, spatial learning, and memory in adolescence and adulthood. In conclusion, early life stage folic acid deficiency had long-term inhibiting effects on neurodevelopment and cognitive function in offspring.<\/jats:p>","DOI":"10.3390\/ijms23136948","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T21:31:06Z","timestamp":1655933466000},"page":"6948","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Early Life Stage Folic Acid Deficiency Delays the Neurobehavioral Development and Cognitive Function of Rat Offspring by Hindering De Novo Telomere Synthesis"],"prefix":"10.3390","volume":"23","author":[{"given":"Dezheng","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenshu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yan","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin 300070, China"},{"name":"Department of Social Medicine and Health Administration, School of Public Health, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China"},{"name":"Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1007\/s43032-020-00161-2","article-title":"Maternal Folic Acid Supplementation Mediates Offspring Health via DNA Methylation","volume":"27","author":"Liu","year":"2020","journal-title":"Reprod. 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