Fig. 7.

Mechanism of mangafodipir on maintaining the primordial follicle reserve. Excessive ROS produced by cisplatin (CIS) and paclitaxel (PTX) led to apoptosis of developing follicles. Apoptosis in developing follicles reduced the amount of inhibitory factors secreted by granulosa cells that activate primordial follicles (such as AMH and inhibin B), and accelerated the activation of primordial follicles and the loss of ovarian reserve. Mangafodipir (M), that possesses SOD2 activity (S), attenuated ROS-induced damage to follicles. Thus, inhibitory factors secreted by developing follicles can inhibit the activation of primordial follicles and maintain normal ovarian reserve. Cisplatin and paclitaxel might have other mechanisms to activate primordial follicles (pink dotted line). And mangafodipir might have other mechanisms that can directly inhibit the activation of primordial follicles (green dotted line)