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To identify placental signatures associated with these outcomes, we performed single\u2010nucleus RNA sequencing on placentas from women with obesity delivering appropriate\u2010for\u2010gestational\u2010age or LGA infants, compared to normal\u2010weight controls. In maternal obesity, regardless of fetal growth, syncytiotrophoblasts showed upregulated hypoxia and TNF\u2010\u03b1 signaling, while cytotrophoblasts exhibited downregulated receptor tyrosine kinase signaling. However, villous non\u2010trophoblasts displayed upregulated TNF\u2010\u03b1 signaling and inflammatory responses only in LGA placentas. Notably, Hofbauer cells in LGA placentas presented transcriptional alterations in immunometabolism\u2010related genes and displayed elevated\n                    <jats:italic>SPP1<\/jats:italic>\n                    expression, which potentially acts as a ligand for other placental cell types. 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