GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288405/suppl/filelist.txtftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288405/suppl/GSE288405_RAW.tarftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288405/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288405GEOGSEfalseMetabolic reprogramming driven by impaired trophoblasts and decidual XCR1+PMN-MDSCs crosstalk controls adverse outcomes in advanced maternal age [CUT&Tag]Decidual 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.2026/04/08GSE288405GSM8766963GSM8766964GSM8766961GSM8766962GSM8766967GSM8766968GSM8766965GSM876696624247288405Mus musculus[41524173]