Effect of bcl-2 on the primordial follicle endowment in the mouse ovary

Little is known about the embryonic factors that regulate the size of the p rimordial follicle endowment at birth. A few studies suggest that members o f the B-cell lymphoma/leukemia-2 (bcl-2) family of protooncogenes may be im portant determinants. Thus, the purpose of this study was to test whether b cl-2 regulates the size of the primordial follicle pool at birth. To test t his hypothesis, three lines of transgenic mice (c-kit/bcl-2 mice) were gene rated that overexpress human bcl-2 in an effort to reduce prenatal oocyte l oss. The overexpression was targeted to the ovary and appropriate embryonic time period with the use of a 4.8-kilobase c-kit promoter. This promoter p rovided two to three times more expression of bcl-2 in the ovaries with min imal or no overexpression in most nongonadal tissues. On Postnatal Days 8-6 0, ovaries were collected from homozygous c-kit/bcl-2 and nontransgenic lit termates (controls) and processed for histological evaluation of follicle n umbers. All lines of c-kit/bcl-2 mice were born with significantly more pri mordial follicles than control mice (P less than or equal to 0.05). By Post natal Days 30-60, however, there were no significant differences in follicl e numbers between c-kit/bcl-2 and control mice. These results indicate that bcl-2 overexpression increases the number of primordial follicles at birth , but that the surfeit of primordial follicles is not maintained in postnat al life. These data suggest that it is possible that the ovary may contain a census mechanism by which excess numbers of primordial follicles at birth are detected and removed from the ovary by adulthood.