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Role of macrophages in ovarian follicular development
H Katabuchi1, Y Fukumatsu, M Araki
1Department of Obstetrics and Gynecology, Kumamoto University School of Medicine, Japan.
Abstract:
The effects of macrophages on granulosa cell proliferation were examined using gonadotropin-primed immature female rats and osteopetrotic (op/op) mice, a model defective in monocyte-macrophage lineage cells. Macrophages were found in the follicles at various developmental stages in rats and mice. The labeling index with [3H]thymidine of cultured rat granulosa cells was maximal when they were cultured with peritoneal macrophages at a macrophages:granulosa cell ratio of 0.01. This ratio was similar to those in rat preantral and antral follicles in vivo. In op/op mice, the number of developing follicles was markedly reduced, but increased after daily macrophage-colony-stimulating factor (M-CSF) administration. In the antral follicles of op/op mice, both granulosa cells and macrophages were significantly decreased in number but were increased after M-CSF treatment. Double immunohistochemical staining revealed that epidermal growth factor (EGF)-positive cells were macrophages in the developing rat follicles. These findings suggest that macrophages are located in the developing follicles and participate in promoting granulosa cell growth through a paracrine mechanism by secreting EGF and other cytokines.
Insights
Macrophages promote granulosa cell proliferation in developing follicles. These immune cells, particularly macrophages, secrete epidermal growth factor (EGF) and cytokines, influencing ovarian follicle development.
Area of Science:
- Reproductive biology
- Immunology
- Cell biology
Background:
- Ovarian follicle development is crucial for female reproduction.
- The role of immune cells, specifically macrophages, in ovarian function is not fully understood.
- Granulosa cells are essential for oocyte development and follicle growth.
Purpose of the Study:
- To investigate the influence of macrophages on granulosa cell proliferation.
- To elucidate the mechanism by which macrophages affect ovarian follicle development.
- To determine the role of macrophage-derived factors, such as epidermal growth factor (EGF), in this process.
Main Methods:
- Experiments utilized gonadotropin-primed immature female rats and osteopetrotic (op/op) mice, a model deficient in macrophages.
- Granulosa cell proliferation was assessed using [3H]thymidine labeling in co-cultures with peritoneal macrophages.
- Macrophage-colony-stimulating factor (M-CSF) was administered to op/op mice to evaluate its effect on follicle development.
- Double immunohistochemical staining was employed to identify EGF-producing cells within developing follicles.
Main Results:
- Macrophages were identified within ovarian follicles at various developmental stages in both rats and mice.
- Co-culture with macrophages significantly enhanced granulosa cell proliferation at a specific ratio (0.01).
- Osteopetrotic mice exhibited reduced follicle numbers, which were restored by M-CSF treatment.
- M-CSF administration also increased granulosa cell and macrophage numbers in antral follicles of op/op mice.
- Macrophages in developing rat follicles were identified as a source of epidermal growth factor (EGF).
Conclusions:
- Macrophages reside in developing ovarian follicles and play a supportive role in granulosa cell proliferation.
- Macrophages promote granulosa cell growth via paracrine mechanisms, likely through the secretion of EGF and other cytokines.
- These findings highlight the intricate interaction between the immune system and reproductive processes, suggesting therapeutic potential for M-CSF in certain ovarian dysfunctions.