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Maternal SD led to adverse effects on offspring health such as cognitive impairment through dysregulated metabolic pathways. However, it remains unknown whether maternal SD increases the offspring's susceptibility to nonalcoholic steatohepatitis (NASH) development. Here, we induced maternal SD during pregnancy and observed that maternal SD during pregnancy promoted the development of diet\u2010induced NASH in offspring of both sexes in adulthood, with exacerbation of liver weight gain, hepatic steatosis, fibrosis, and hepatic dysfunction. The primary hepatocytes isolated from SD offspring were also more susceptible to palmitate acid\u2010induced lipotoxic injury. Mechanistically, the detrimental effects of maternal SD were associated with augmented activation of inflammatory and apoptosis pathways in offspring liver tissues, which were attributed to upregulation of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). The melatonin signalling is reported to be pivotally affected by sleep disturbance both at the circulation and the placenta, and our further analysis revealed that melatonin supplementation during maternal SD normalised NR4A3 expression in offspring liver and alleviated the increased steatohepatitis susceptibility in offspring. Taken together, these results suggest that maternal SD during pregnancy predisposes offspring to NASH development in adulthood via an NR4A3\u2010dependent mechanism, and maternal melatonin supplementation may hold promise for improving liver health in the offspring.<\/jats:p>","DOI":"10.1111\/cpr.70138","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T13:23:41Z","timestamp":1761657821000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gestational Melatonin Supplementation Attenuates Maternal Sleep Deprivation\u2010Induced Steatohepatitis Susceptibility in Offspring"],"prefix":"10.1111","volume":"59","author":[{"given":"Fei","family":"Guo","sequence":"first","affiliation":[{"name":"Obstetrics &amp; Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Institute of Reproduction and Development, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zexin","family":"Yang","sequence":"additional","affiliation":[{"name":"Obstetrics &amp; Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Institute of Reproduction and Development, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junsen","family":"She","sequence":"additional","affiliation":[{"name":"International Institutes of Medicine, the Fourth Affiliated Hospital, Zhejiang University School of Medicine  Yiwu China"},{"name":"Institute of Medical Genetics and Development, Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Hospital, Zhejiang University School of Medicine  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Development, Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Hospital, Zhejiang University School of Medicine  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhi","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Development, Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Hospital, Zhejiang University School of Medicine  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hefeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Obstetrics &amp; Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Institute of Reproduction and Development, Fudan University  Shanghai China"},{"name":"International Institutes of Medicine, the Fourth Affiliated Hospital, Zhejiang University School of Medicine  Yiwu China"},{"name":"Institute of Medical Genetics and Development, Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Hospital, Zhejiang University School of Medicine  Zhejiang China"},{"name":"Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056)  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Gao","sequence":"additional","affiliation":[{"name":"Obstetrics &amp; Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Institute of Reproduction and Development, Fudan University  Shanghai China"},{"name":"Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056)  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.04.036"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.009"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17158"},{"issue":"6","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/s41575-023-00787-y","article-title":"NAFLD Incidence Is Increasing","volume":"20","author":"Kotsiliti E.","year":"2023","journal-title":"Nature Reviews Gastroenterology & Hepatology"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00639-3"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11901-020-00539-5"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.012"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.12.009"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.065827"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.06.045"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107974"},{"issue":"2","key":"e_1_2_11_13_1","first-page":"323","article-title":"Maternal High\u2010Fat Diet Triggers Lipotoxicity in the Fetal Livers of Nonhuman Primates","volume":"119","author":"McCurdy C. 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