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Notably, the addition of melatonin to culture medium may improve embryo development and prevent cardiovascular dysfunction in IVF adult mice. This study aimed to determine if melatonin supplementation in the culture medium can reverse impaired glucose metabolism in IVF mice offspring and the underlying mechanisms. Blastocysts used for transfer were generated by natural mating (control group) or IVF with or without melatonin (10<jats:sup>\u22126<\/jats:sup>\u00a0M) supplementation (mIVF and IVF group, respectively) in clinical\u2010grade culture media. Here, we first report that IVF decreased hepatic expression of <jats:italic>Fbxl7<\/jats:italic>, which was associated with impaired glucose metabolism in mice offspring. Melatonin addition reversed the phenotype by up\u2010regulating the expression of hepatic <jats:italic>Fbxl7<\/jats:italic>. In vitro experiments showed that <jats:italic>Fbxl7<\/jats:italic> enhanced the insulin signaling pathway by degrading <jats:italic>RhoA<\/jats:italic> through ubiquitination and was up\u2010regulated by transcription factor <jats:italic>Foxa2<\/jats:italic>. Specific knockout of <jats:italic>Fbxl7<\/jats:italic> in the liver of adult mice, through tail intravenous injection of recombinant adeno\u2010associated virus, impaired glucose tolerance, while overexpression of hepatic <jats:italic>Fbxl7<\/jats:italic>\u00a0significantly improved glucose tolerance in adult IVF mice. Thus, the data suggest that <jats:italic>Fbxl7<\/jats:italic> plays an important role in maintaining glucose metabolism of mice, and melatonin supplementation in the culture medium may rescue the long\u2010term risk of metabolic diseases in IVF offspring.<\/jats:p>","DOI":"10.1111\/jpi.12778","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T21:05:35Z","timestamp":1635887135000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Melatonin supplementation in the culture medium rescues impaired glucose metabolism in IVF mice offspring"],"prefix":"10.1111","volume":"72","author":[{"given":"Yanping","family":"Jia","sequence":"first","affiliation":[{"name":"Centre for Assisted Reproduction Shanghai First Maternity and Infant Hospital School of Medicine Tongji University Shanghai 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