ROLE OF MACROPHAGES IN OVARIAN FOLLICULAR DEVELOPMENT

The effects of macrophages on granulosa cell proliferation were examin ed using gonadotropin-primed immature female rats and osteopetrotic (o p/op) mice, a model defective in monocyte-macrophage lineage cells. Ma crophages were found in the follicles at various developmental stages in rats and mice. The labeling index with [H-3]thymidine of cultured r at 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. I n 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 granulos a cells and macrophages were significantly decreased in number but wer e increased after M-CSF treatment. Double immunohistochemical staining revealed that epidermal growth factor (EGF)-positive cells were macro phages in the developing rat follicles. These findings suggest that ma crophages are located in the developing follicles and participate in p romoting granulosa cell growth through a paracrine mechanism by secret ing EGF and other cytokines.