Gonadotropin stimulation as a challenge to calibrate cisplatin induced ovarian damage in the female rat.

Cisplatin administration for treatment of cancer causes damage to the ovaries, potentially leading to ovarian failure. To extend our previous work, we tested the hypothesis that serum anti-Mullerian hormone (AMH) levels after ovarian stimulation can be used as a biomarker to calibrate the degree of ovarian damage following cisplatin. Female rats were injected with two weekly doses of cisplatin followed by an injection of pregnant mare serum gonadotropin to stimulate the ovaries. Sera and ovaries were collected 54 h after gonadotropin challenge. Analysis of serum and ovarian AMH by Western blot and ELISA revealed that increasing doses of cisplatin caused dose-dependent decrease in AMH after gonadotropin stimulation. Immunohistochemical analysis demonstrated that the AMH positive follicles declined in a dose-dependent manner after cisplatin, resulting in AMH levels that are lower after cisplatin exposure. Cisplatin damage to the ovaries can be identified by the serum AMH levels following exogenous ovarian stimulation.