Baseline and stimulated serum inhibin levels as biomarkers of cisplatin-induced ovarian damage in female rats.

Abstract

OBJECTIVE: Chemotherapeutic agents, such as cisplatin, injure the ovary. It was hypothesized that serum inhibins can serve as biomarkers of ovarian damage from cisplatin. STUDY DESIGN: Adult female rats were administered cisplatin and afterward pregnant mare serum gonadotropin (PMSG) was given to stimulate ovarian inhibin production. RESULTS: At baseline, the serum inhibin A levels in the cisplatin-treated groups were slightly lower than saline. However, after PMSG stimulation, the cisplatin groups had dose-related and significantly blunted serum inhibin A and B responses. Results of Western blot and enzyme-linked immunosorbent assay inhibin analysis of ovarian lysate were consistent with the serum levels. Investigation of the ovaries showed that cisplatin groups at baseline had higher percentages of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling-positive follicles in inhibin positive follicles, suggesting that cisplatin induced apoptosis in the inhibin follicles. CONCLUSION: We conclude that serum inhibin A and B after PMSG ovarian challenge can be used as biomarkers to define rat ovarian damage after exposure to cisplatin.