The female reproductive tract undergoes dramatic cycles of growth and degeneration in which apoptosis plays an important regulatory role. In the ovary, apoptosis is responsible for the marked germ cell attrition during fetal life, which determines the size of the resting follicle stock. The number of resting follicles continuously decreases through follicle atresia and ultimately only about 400 follicles out of 7 million will survive and ovulate.
In adult ovaries, apoptosis was mainly detected in granulosa cells of large growing follicles, and no apoptosis was observed in the oocytes. However, a low rate of oocyte apoptosis cannot be ruled out, and possibly this process continues until menopause. It is likely that follicular atresia of unselected follicles is primarily caused by granulosa cell apoptosis and not oocyte demise. Ovaries non-responsive to FSH did not show follicular development or granulosa cell apoptosis, suggesting that in adult life apoptosis controls cell/tissue homeostasis, and the rate of apoptosis is related to cell proliferation.
After ovulation, the dominant follicle collapses and forms the CL. If pregnancy does not occur, CL regression takes place to allow new follicles to be recruited during the next menstrual cycle. CL regression takes place by an apoptotic mechanism that is possibly regulated by TNF-_ and E2.
In the endometrium, superficial layers are shed during menstruation to permit growth of new endometrium to ensure the highest receptivity at the time of ovulation. A high rate of apoptosis was detected in menstrual endometrium, indicating a role for programmed cell death in this process. This increase in apoptosis was preceded by a decrease in the Bcl-2/Bax ratio. Although direct evidence is missing, it seems likely that in the endometrium these apoptosis-regulating factors are under the control of ovarian steroids. In endometrial hyperplasia, the rate of apoptosis was equal to that seen in normal proliferating endometrium, but in grade II carcinoma it was significantly increased. This may reflect a mechanism to maintain cell homeostasis, the control of which is probably disturbed or lost in more advanced carcinomas.