Fig. 8. Proposal model.

Concomitant administration of GNF-2 and cyclophosphamide results in the inhibition of the AKT-FOXO3a signaling axis and DDR, thereby preventing cyclophosphamide-induced apoptosis of oocyte reserve. On the contrary, DPH enhanced the activation of the AKT-FOXO3a signaling axis and DDR response following cyclophosphamide injection. Oocyte reserve was positive for both p-AKT/p-FOXO3a and p-ATM/γH2AX; thus, the presence of the early marker of DDR was consistent with the activation of the AKT-FOXO3 pathway. This observation suggests that oocytes leave their follicular quiescence to initiate the DNA damage signaling pathway that leads to oocyte apoptosis