Single-cell analysis of ovarian myeloid cells identifies aging associated changes in macrophages and signaling dynamics

The aging of mammalian ovary is accompanied by an increase in tissue fibrosis and heightened inflammation. Myeloid cells, including macrophages, monocytes, dendritic cells, and neutrophils, play pivotal roles in shaping the ovarian tissue microenvironment and regulating inflammatory responses. However, a comprehensive understanding of the roles of these cells in the ovarian aging process is lacking. To bridge this knowledge gap, we utilized single-cell RNA sequencing (scRNAseq) and flow cytometry analysis to functionally characterize CD45 ⁺ CD11b ⁺ myeloid cell populations in young (3 months old) and aged (14-17 months old) murine ovaries. Our dataset unveiled the presence of five ovarian macrophage subsets, including a Cx3cr1 ^low Cd81 ^hi subset unique to the aged murine ovary. Most notably, our data revealed significant alterations in ANNEXIN and TGFβ signaling within aged ovarian myeloid cells, which suggest a novel mechanism contributing to the onset and progression of aging-associated inflammation and fibrosis in the ovarian tissue.