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Published on: July 29, 2018
Ovarian monocyte progenitor cells: phenotypic and functional characterization
Cherry J Pascual1, Paul R Sanberg, Wilfredo Chamizo
1Department of Pediatrics, University of South Florida, St. Petersburg, FL 33612, USA.
Abstract:
Leukocytes of the macrophage lineage are abundant in the ovarian tissues and have an important function in both follicular development and regression of postovulatory follicles. In this study, we tested the hypothesis that continuous production of macrophages in the ovarian stroma is maintained by a resident population of progenitors. We established a long-term culture of ovarian follicular stromal cells from BALB/c and green fluorescent protein-transgenic (GFP-TG) C57BL/6 mice. Nonadherent cells were collected and tested for hematopoietic function in vitro and in vivo. Histological and ultrastructural analyses revealed a homogenous population of monocyte-like rounded cells. Nonadherent cells continued to proliferate in culture for several months without senescence. When plated at very low density in methylcellulose, these cells formed colonies consisting of monocyte-like cells. Ovarian monocyte-like cells reacted with CD45, CD11b, CD11c, and Ly6-Gr-1 cell surface markers. A distinct CD45low population within these cells reacted with CD117 (C-kit) surface marker, suggestive of a primitive hematopoietic progenitor. Fifty thousand nonadherent cells failed to provide radioprotection to lethally irradiated mice and thus were not considered to be equivalent to pluripotent hematopoietic stem cells. Ovarian nonadherent stromal cells were positive for alkaline phosphatase but lacked embryonic cell antigens stage-specific embryonic antigen (SSEA-1) and Oct-4. We conclude that in the ovaries, a higher requirement for macrophages is provided by a resident stromal population of progenitors whose progeny is restricted to the production of cells of the monocyte-macrophage lineage.
Insights
Ovarian stromal cells contain progenitor cells that continuously produce macrophages, essential for ovarian function. These progenitors are lineage-restricted, differentiating only into monocyte-macrophage cells within the ovary.
Area of Science:
- Reproductive biology
- Hematopoiesis
- Cell biology
Background:
- Macrophages are crucial for ovarian functions, including follicular development and postovulatory follicle regression.
- The continuous presence of macrophages suggests a self-sustaining production mechanism within the ovarian stroma.
Purpose of the Study:
- To investigate the hypothesis that resident progenitor cells in the ovarian stroma maintain the continuous production of macrophages.
- To characterize the nature and hematopoietic potential of nonadherent ovarian stromal cells.
Main Methods:
- Long-term culture of ovarian follicular stromal cells from BALB/c and GFP-transgenic mice.
- Analysis of nonadherent cell proliferation, colony formation, and surface marker expression (CD45, CD11b, CD11c, Ly6-Gr-1, CD117/C-kit).
- In vivo radioprotection assays and assessment of embryonic cell antigens (SSEA-1, Oct-4).
Main Results:
- Nonadherent ovarian stromal cells proliferated extensively without senescence and formed monocyte-like cell colonies.
- These cells expressed macrophage lineage markers (CD45, CD11b, CD11c, Ly6-Gr-1) and a primitive progenitor marker (CD117).
- The cells lacked pluripotent hematopoietic stem cell activity and embryonic stem cell markers.
Conclusions:
- The ovarian stroma harbors a resident progenitor population dedicated to monocyte-macrophage production.
- These progenitors are lineage-restricted, ensuring a consistent supply of macrophages for ovarian tissue maintenance and function.
