GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE289nnn/GSE289975/suppl/filelist.txtftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE289nnn/GSE289975/suppl/GSE289975_RAW.tarftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE289nnn/GSE289975/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289975GEOGSEfalseMetabolic reprogramming driven by impaired trophoblasts and decidual XCR1+PMN-MDSCs crosstalk controls adverse outcomes in advanced maternal ageDecidual polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are crucial for maternal–fetal stability and accumulate to support fetal development. Although advanced maternal age (AMA) increases the risk of adverse outcomes, the regulatory role and mechanism of decidual PMN-MDSCs in these outcomes remain unclear. Herein, the XCL1–XCR1 interaction mediated specific crosstalk between trophoblast cells and decidual PMN-MDSCs in both humans and mice. Single-cell sequencing identified a decidual PMN-MDSCs subset highly expressing XCR1 markedly reduced in AMA. Impaired XCL1-stimulated decidual XCR1+PMN-MDSCs delayed fetal growth in AMA and Xcr1-/- pregnant mice. Perinatal XCL1 supplementation and oltipraz treatment rescued these functions by activating decidual XCR1+PMN-MDSCs in AMA mice, not Xcr1-/- pregnant mice. The XCL1–XCR1 axis induced FOXO1 nuclear localization, regulating oxidative phosphorylation-related targets and enabling metabolic processes. Hence, XCL1–XCR1 crosstalk between trophoblast cells and PMN-MDSCs is critical in driving metabolic reprogramming of decidual XCR1+PMN-MDSCs and controlling adverse outcomes caused by AMA.2026/04/08GSE289975GSM8802810GSM8802806GSM8802808GSM8802807GSM880280929480289975Homo sapiens[41524173]