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We previously found that children with autism spectrum disorder (ASD) have a significant rate of VA deficiency (VAD). In the current study, we aim to determine whether VAD is a risk factor for the generation of autistic\u2010like behaviors via the transcription factor retinoic acid receptor beta (RAR\u03b2)\u2010regulated cluster of differentiation 38 (CD38)\u2010oxytocin (OXT) axis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Gestational VAD or VA supplementation (VAS) rat models are established, and the autistic\u2010like behaviors in the offspring rats are investigated. The different expression levels of RAR\u03b2 and CD38 in hypothalamic tissue and serum retinol and OXT concentration are tested. Primary cultured rat hypothalamic neurons are treated with all\u2010trans retinoic acid (atRA), and recombinant adenoviruses carrying the rat RAR\u03b2 (AdRAR\u03b2) or RNA interference virus RAR\u03b2\u2010siRNA (siRAR\u03b2) are used to infect neurons to change RAR\u03b2 signal. Western blotting, chromatin immunoprecipitation (ChIP), and intracellular Ca<jats:sup>2+<\/jats:sup> detections are used to investigate the primary regulatory mechanism of RAR\u03b2 in the CD38\u2010OXT signaling pathway. We found that gestational VAD increases autistic\u2010like behaviors and decreases the expression levels of hypothalamic RAR\u03b2 and CD38 and serum OXT levels in the offspring. VAS ameliorates these autistic\u2010like behaviors and increases the expression levels of RAR\u03b2, CD38, and OXT in the gestational VAD pups. In vitro, atRA increases the Ca<jats:sup>2+<\/jats:sup> excitability of neurons, which might further promote the release of OXT. Different CD38 levels are induced in the neurons by infection with different RAR\u03b2 adenoviruses. Furthermore, atRA enhances the binding of RAR\u03b2 to the proximal promoter of CD38, indicating a potential upregulation of CD38 transcriptional activity by RAR\u03b2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Gestational VAD might be a risk factor for autistic\u2010like behaviors due to the RAR\u03b2 signal suppression of CD38 expression in the hypothalamus of the offspring, which improves with VAS during the early\u2010life period. The nutritional status during pregnancy and the early\u2010life period is important in rats.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201700754","type":"journal-article","created":{"date-parts":[[2017,12,23]],"date-time":"2017-12-23T13:41:55Z","timestamp":1514036515000},"source":"Crossref","is-referenced-by-count":46,"title":["Vitamin A Deficiency Induces Autistic\u2010Like Behaviors in Rats by Regulating the RAR\u03b2\u2010CD38\u2010Oxytocin Axis in the Hypothalamus"],"prefix":"10.1002","volume":"62","author":[{"given":"Xi","family":"Lai","sequence":"first","affiliation":[{"name":"Children's Nutrition Research Center Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education Key Laboratory of Child Development and Disorders China International Science and Technology Cooperation base of Child Development and Critical Disorders  Chongqing 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