Two distinct resident macrophage populations coexist in the ovary

INTRODUCTION: Tissue-resident macrophages (TRMs) are highly heterogeneous and have a complex and important role in tissue support, homeostasis, and function. The heterogeneity, maintenance, and function of TRMs, as one of the major immune cells in the ovary, are not well understood. METHODS: Application of flow cytometry, Parabiosis, Fate mapping, Macrophage depletion, etc. RESULTS: Here, we described two distinct macrophage subsets, F4/80(hi)CD11b(int) and F4/80(int)CD11b(hi), with different phenotypic characteristics in the ovary of mice. The F4/80(hi)CD11b(int) population contained a distinct CD206(+) subgroup and highly expressed CD81, while the F4/80(int)CD11b(hi) subset showed higher expression of CCR2 and TLR2. Notably, Ly6c(+) macrophages were present almost exclusively in the F4/80(int)CD11b(hi) subpopulation. Combining in vivo fate mapping and parabiotic mouse models, we characterized the longevity and replenishment of the two macrophage populations. We found that both the F4/80(hi)CD11b(int) and F4/80(int)CD11b(hi) subsets were ovary-resident. Importantly, the F4/80(hi)CD11b(int) macrophages acted as a self-maintaining and long-lived population with a modest monocyte contribution at a steady state, and the F4/80(int)CD11b(hi) subpopulation had a relatively short lifespan with a greater contribution from monocytes. After macrophage ablation, disturbance of estradiol secretion and ovarian hemorrhage due to damaged vascular integrity was observed in mice. DISCUSSION: Our data provide critical insights into ovarian macrophage heterogeneity and highlight the strategic role of TRMs in ovarian homeostasis and physiology.