Elimination of apoptotic granulosa cells by intact granulosa cells and macrophages in atretic mature follicles of the guinea pig ovary.

Abstract

Phagocytic cells disposing of dying granulosa cells in the atretic ovarian follicles were morphologically studied in guinea pig ovaries at various stages of estrous cycle. Epon embedded semithin sections stained with toluidine blue were observed with a light microscope, and ultrathin sections were examined under a transmission electron microscope. Frozen sections were processed for acid phosphatase histochemistry and MR-1 (a monoclonal antibody against guinea pig macrophages) immunohistochemistry. In animals during the estrus period (days 1 and 2) as well as the second half of the estrous cycle (days 11 and 16), there were numerous mature follicles in which massive groups of granulosa cells were undergoing apoptosis. Two kinds of phagocytic cells were identified in these follicles of the initial stage of atresia: one was intact granulosa cells ingesting neighboring dead granulosa cells, and the other was large round cells identified as macrophages due to their strong acid phosphatase activity and MR-1 immunoreactivity. Mature follicles of the advanced stage of atresia were frequently recognized during the metestrus period (days 4 and 5). Small stellate cells were regarded as surviving granulosa cells, while large round cells showing intense reactions for acid phosphatase and MR-1 were identified as macrophages. This study demonstrates that both intact granulosa cells and macrophages participate in the elimination of apoptotic granulosa cells in atretic mature follicles of the guinea pig ovary, and remain even in the advanced stages of atresia.