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Pregnant C57BL\/6N mice were treated with ammonium tetrathiomolybdate to induce copper deficiency, with two different dosages (30 and 60\u00a0mg\u00b7kg\u22121\u00b7d\u22121) administered daily from gestational day 1 to day 14. On day 15, assessments were made on fetal growth, placental development, and spatial metabolomics. In parallel, trophoblast cells (HTR8\/SVneo) were subjected to copper chelation or SLC31A1 knockdown to model copper deficiency in vitro. Cell invasiveness and proliferation were evaluated using appropriate assays, along with the measurement of molecular markers to assess the impact of copper deficiency. Copper deficiency significantly reduced maternal serum copper levels, leading to FGR, as evidenced by shorter crown-rump lengths, lower fetal weights, and altered fetal-to-placental weight ratios. Structural abnormalities in the placental junctional zone, including reduced size and altered morphology, were observed. Metabolomic analysis revealed disrupted lipid metabolism, with alterations in glycerophospholipids and fatty acids, and lipid droplet accumulation. Copper deficiency impaired trophoblast migration and invasion, linked to decreased MMP2 and MMP9 expression in vivo and in vitro. In vitro studies also showed altered lipid metabolism in SLC31A1-knockdown trophoblast cells. Copper deficiency disrupts placental structure and lipid metabolism, impairs trophoblast function, and contributes to FGR, highlighting the critical role of copper in fetal development and maternal health.<\/jats:p>","DOI":"10.1093\/biolre\/ioag096","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T11:31:28Z","timestamp":1777980688000},"page":"483-499","source":"Crossref","is-referenced-by-count":2,"title":["Copper deficiency disrupts placental development and lipid metabolism, contributing to fetal growth restriction"],"prefix":"10.1093","volume":"115","author":[{"given":"Yu-Jie","family":"Ran","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Women and Children\u2019s Hospital of Chongqing Medical University, Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University , Chongqing 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Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University , Chongqing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En-Xiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, School of Basic Medicine, Chongqing Medical University , Chongqing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Fang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Women and Children\u2019s Hospital of Chongqing Medical University, Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University , Chongqing 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