It is generally accepted that significant germ cell loss occurs during the establishment of the primordial follicle pool in most mammalian ovaries around the time of birth. However, the underlying mechanisms responsible for these processes remain largely unknown. In this investigation, we explored the role of autophagy during the establishment of the primordial follicle pool and found that autophagy was active in this process. Our data suggested that 17.5 dpc ovaries treated with rapamycin displayed a delay in germ cell cyst breakdown resulting in more oocytes at day 5 of treatment, while, ovaries that treated with 3-MA showed the opposite effect. We found that rapamycin treatment promoted autophagy and depressed cell apoptosis increasing the number of NOBOX positive oocytes. Furthermore, our results also revealed that epigenetic regulator, Sirt1, plays a role in germ cell loss. An epigenetic inhibitor or RNAi treatment of Sirt1, showed an increased level of H4K16ac and a decreased level of autophagy. Thus, these data indicate that autophagy prevents germ cell over loss during the establishment of primordial follicle pool, and this process may be influenced by Sirt1-invovled epigenetic regulation.
Keywords: apoptosis; autophagy; epigenetic regulation; germ cell cyst breakdown; primordial follicle.