Ovarian follicle macrophages: is follicular atresia in the immature rat a macrophage-mediated event?

Macrophages have recently been found to play roles in most ovarian events through cytokine release and/or cell-cell communication. We studied the presence of macrophages in the ovaries of neonatal (0-7 days of age), juvenile (10-20 days of age), and prepubertal (25-30 days of age) rats, as well as adult cycling rats, in relation to follicular development and atresia. Macrophages were extremely scarce in the ovarian stroma up to 30 days of age. However, at 10 days of age, about 13% of small growing healthy follicles contained macrophages among granulosa cells. The percentage of macrophage-containing follicles at 15 days of age was about 60%, and the vast majority of these follicles also had pyknotic granulosa cells, which increased in number from 15 to 20 days of age. This type of atresia showed distinctive morphological and functional features in comparison with the atretic process observed in adult cycling rats. At 25 and 30 days of age, atretic follicles in advanced stages of atresia, together with atretic follicles similar to those present in adult rats, were observed. In adult rats, only a small proportion of healthy growing follicles contained macrophages. These cells were absent from early atretic follicles, and invasion by macrophages occurred at advanced stages of atresia. These data indicate that a different type of atresia occurred during early postnatal development, probably related to the special endocrine environment in immature rats. The close association between the presence of macrophages inside the follicles and of apoptotic granulosa cells strongly supports the hypothesis that macrophages mediate follicular atresia in immature rats.