Evidence for widespread atresia in the hypophysectomized estrogen-treated rat

The question considered in this study concerns to what extent the ovaries of the immature hypophysectomized diethylestilbestrol-treated rat are populated by atretic follicles. Histological studies of ovaries on postoperative days 4-7 reveal the presence of numerous follicles showing signs of ill health. The granulosa cells constituting these follicles are heterogeneous and exist in three distinct zones. The cells in zone 1 are affixed to the basal lamina and form a tightly packed sheet of cuboidal epithelium one to two cells thick. The cells constituting zone 2 are located just medial to zone 1 and appear as a mass of loosely aggregated cells which show intense necrosis. Zone 3 is composed of the prospective cumulus-oocyte complex which appears completely normal. Results of histochemical studies show heterogeneity in the granulosa cells with respect to the presence and location of markers specific for atresia. In atretic follicles, the granulosa cells populating zones 1 and 2 contain lipid droplets and esterase activity, but are negative for the lysosomal enzyme acid phosphatase. The exact reverse is true for zone 3, where the cumulus express intense acid phosphatase activity but are negative for lipid and esterase activities. The granulosa cells in healthy follicles are totally negative for these histochemical markers. As a healthy preantral follicle grows, there is a dramatic increase in the mitotic index of the granulosa cells; however, in all atretic follicles, granulosa cell division is decreased by more than 90%. Further experiments using monoclonal antibodies as probes confirm the presence of atretic follicles and demonstrate that the structure-function changes in zones 1 and 2 are associated with striking changes in the antigenic properties of the granulosa cells. Morphometric studies indicate there are a total of 235 +/- 29 preantral follicles/ovary in the hypophysectomized diethylstilbestrol-treated rat. On postoperative day 4, 37 +/- 1.2% of the preantral follicles are atretic; this number increases linearly with time posthypophysectomy, reaching nearly 50% on postoperative day 7. Examination of follicles at different stages of development reveals that atresia is rare in the very early stages, e.g. follicles less than 200 microns in diameter; however, in the population of larger preantral follicles (those 200-400 microns in diameter), atresia is common, with nearly 80% being atretic on postoperative day 7. Collectively, these findings provide convincing evidence of widespread atresia in the ovaries of the hypophysectomized diethylstilbestrol-treated rat.(ABSTRACT TRUNCATED AT 400 WORDS)