Molecular Basis Associated with the Control of Primordial Follicle Activation During Transplantation of Cryopreserved Ovarian Tissue

Cryopreservation and transplantation of ovarian tissue represent a promising fertility preservation technique for prepubertal patients or for patients requiring urgent oncological management. However, this technique has some limitations, including follicular loss directly after transplantation mainly due to ischaemic damage but also due to activation of primordial follicles (also known as follicular burnout), leading to follicular reserve loss in the graft and thereby potentially reducing its lifespan. In vitro and in vivo studies indicate that the phosphatidylinositol-3-kinase (PI3K)/phosphatase and tensin homologue (PTEN)/Akt, mammalian target of rapamycin (mTOR), c-Jun-N-terminal kinase (JNK), and Hippo signalling pathways are involved in primordial follicle activation. Here, we review the basic mechanisms linked to the follicle activation that occurs after cryopreservation and transplantation of ovarian tissue. A better understanding of the crosstalk between the different signalling pathways may lead to potential improvement of fertility restoration by extending graft lifespan through selective control of the activation of dormant follicles after transplantation of cryopreserved ovarian tissue.