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Defects in the syncytiotrophoblast, which is pivotal for maternal\u2010fetal substance exchange, adversely affect fetal development. Whether dysfunction in syncytiotrophoblast is involved in GHG\u2010related FGR remains unclear. In this study, we used an STZ\u2010induced GHG mouse model and found that GHG\u2010induced FGR (44.5% reduction in fetal weight) was associated with a 28.3% decrease in placental efficiency. Immunofluorescence and transmission electron microscopy examinations revealed defective formation of the syncytiotrophoblast layer in GHG placenta, resulting from impaired fusion of trophoblast cells. Gene expression profiling and staining analysis of the placenta revealed that\n                    <jats:italic>Tim1<\/jats:italic>\n                    , a phosphatidylserine\u2010binding protein, was 43.5% downregulated in GHG placenta. In vitro studies confirmed that hyperglycemia decreased\n                    <jats:italic>Tim1<\/jats:italic>\n                    and led to trophoblast fusion defects.\n                    <jats:italic>Tim1<\/jats:italic>\n                    silence alone recapitulated the effects of hyperglycemia on trophoblast fusion, while\n                    <jats:italic>Tim1<\/jats:italic>\n                    overexpression rescued the anti\u2010fusion effects of hyperglycemia. Moreover, we generated a\n                    <jats:italic>Tim1<\/jats:italic>\n                    knockout mouse strain, and observed that\n                    <jats:italic>Tim1<\/jats:italic>\n                    deficiency alone induced defective formation of syncytiotrophoblast and FGR during pregnancy. Further analysis revealed that\n                    <jats:italic>Tim1<\/jats:italic>\n                    was downregulated by hyperglycemia\u2010related oxidative stress. Antioxidant treatment during pregnancy reversed\n                    <jats:italic>Tim1<\/jats:italic>\n                    downregulation, promoted syncytiotrophoblast formation and improved FGR. Finally, the reduction of\n                    <jats:italic>TIM1<\/jats:italic>\n                    expression was confirmed in human placenta with pre\u2010gestational diabetes and FGR. These findings suggest that\n                    <jats:italic>Tim1<\/jats:italic>\n                    downregulation in GHG inhibits placental syncytiotrophoblast formation and contributes to FGR.\n                  <\/jats:p>","DOI":"10.1002\/advs.202508686","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T09:59:58Z","timestamp":1770803998000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>Tim1<\/i>\n                    Deficiency Mediates Gestational Hyperglycemia\u2010Related Syncytiotrophoblast Dysfunction and Fetal Growth Restriction"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3146-7664","authenticated-orcid":false,"given":"Junsen","family":"She","sequence":"first","affiliation":[{"name":"Center for Reproductive Medicine International Institutes of Medicine The Fourth Affiliated Hospital Zhejiang University School of Medicine  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