Fetal-derived macrophages persist and sequentially maturate in ovaries after birth in mice
Heli Jokela1,2, Emmi Lokka1,3,2, Miikka Kiviranta1
1Institute of Biomedicine, University of Turku, Turku, Finland.
Abstract:
Macrophages, which are highly diverse in different tissues, play a complex and vital role in tissue development, homeostasis, and inflammation. The origin and heterogeneity of tissue-resident monocytes and macrophages in ovaries remains unknown. Here we identify three tissue-resident monocyte populations and five macrophage populations in the adult ovaries using high-dimensional single cell mass cytometry. Ontogenic analyses using cell fate mapping models and cell depletion experiments revealed the infiltration of ovaries by both yolk sac and fetal liver-derived macrophages already during the embryonic development. Moreover, we found that both embryonic and bone marrow-derived macrophages contribute to the distinct ovarian macrophage subpopulations in the adults. These assays also showed that fetal-derived MHC II-negative macrophages differentiate postnatally in the maturing ovary to MHC II-positive cells. Our analyses further unraveled that the developmentally distinct macrophage types share overlapping distribution and scavenging function in the ovaries under homeostatic conditions. In conclusion, we report here the first comprehensive analyses of ovarian monocytes and macrophages. In addition, we show that the mechanisms controlling monocyte immigration, the phenotype of different pools of interstitial macrophages, and the interconversion capacity of fetal-derived macrophages in ovaries are remarkably different from those seen in other tissue niches.
Insights
This study reveals the diverse origins and types of ovarian macrophages, identifying both embryonic and adult bone marrow contributions. These ovarian macrophages have unique developmental pathways and functions distinct from other tissues.
Area of Science:
- Immunology
- Developmental Biology
- Reproductive Biology
Background:
- Macrophages are crucial for tissue health, yet their specific roles and origins in ovaries are unclear.
- Understanding ovarian macrophage heterogeneity is vital for reproductive health and disease research.
Purpose of the Study:
- To comprehensively characterize the origin, diversity, and function of tissue-resident monocytes and macrophages in adult ovaries.
- To elucidate the developmental trajectories and interconversion capacity of ovarian macrophages.
Main Methods:
- High-dimensional single-cell mass cytometry was employed to identify distinct monocyte and macrophage populations.
- Cell fate mapping models and cell depletion experiments were used for ontogenic analyses.
- Functional assays investigated macrophage distribution and scavenging roles under homeostatic conditions.
Main Results:
- Three tissue-resident monocyte and five distinct macrophage populations were identified in adult ovaries.
- Ovarian macrophages originate from both embryonic (yolk sac, fetal liver) and adult (bone marrow) sources.
- Embryonic-derived macrophages undergo postnatal maturation, changing from MHC II-negative to MHC II-positive phenotypes, with overlapping functions.
Conclusions:
- This is the first comprehensive analysis of ovarian monocytes and macrophages, detailing their complex origins and heterogeneity.
- Ovarian macrophages exhibit unique immigration mechanisms, interstitial phenotypes, and interconversion capacities compared to other tissues.
- These findings provide a foundational understanding of ovarian immune cell dynamics in development and homeostasis.
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