Müllerian inhibiting substance as a novel biomarker of cisplatin-induced ovarian damage

Müllerian inhibiting substance (MIS) has been investigated as a possible serum biomarker in human aging to estimate the number of female germ cells remaining. Cisplatin is an effective chemotherapeutic agent that is associated with ovarian injury. In this study, we tested the hypothesis that decreasing serum MIS can serve as a biomarker of ovarian damage after cisplatin. Adult female rats were treated with saline, 4.5, or 6.0 mg/kg cisplatin. The serum MIS levels were lower in both cisplatin groups, in a dose-related fashion. The ovarian lysates of both cisplatin groups had less MIS than control. Immunofluorescence analysis showed that the percentage of MIS-positive follicles was lower in the 6.0 mg/kg group. TUNEL assays showed that there was a dose related increase in the number of apoptotic follicles in the cisplatin groups. In summary, a decrease in serum MIS could serve as a biomarker to discriminate the degree of ovarian damage after cisplatin. These data are the first to establish in the rat that ovarian injury due to a chemotherapeutic agent could be monitored with the non-invasive serum biomarker MIS.