Induction of apoptosis and ovarian cyst formation in the mouse ovary by dehydroepiandrosterone (DHEA).

Exogenous dehydroepiandrosterone (DHEA) produces ovarian cysts and atretic follicles in mice. We sought to test the hypothesis that the abnormal follicular development found after DHEA administration in mice results from aberrant ovarian apoptosis. DHEA was injected subcutaneouly for 15 days. Controls received an equivalent volume of vehicle. Follicle size was measured, and the proportion of ovarian follicles containing apoptotis was assessed by in situ end-labeling of DNA. DHEA resulted in a greater proportion of follicles with evidence of apoptosis (62.4% in the DHEA group [n = 789 follicles] vs. 53.0% in the vehicle group [n = 440 follicles]; p = 0.031). DHEA also produced larger follicles (mean diameter: 234.7um +/- 24.6um in the DHEA group vs. 204.6um +/- 11.4um in the vehicle group; p < 0.01). All of the DHEA-treated mice contained follicles > 500um while only one of the mice in the vehicle group contained a follicle > 500um in diameter (p < 0.001). We conclude that DHEA administration results in increased ovarian apoptosis and in larger follicle size, thereby producing a characteristic cystic and atretic appearance in the mouse ovary. This may be the mechanism by which androgens cause ovarian cyst formation.