Biological pathways regulating gamete quality during the pubertal transition

Reproductive aging is characterized as age-related loss of fertility as a result of increased damage to the reproductive and other systems. Oocytes accumulate damage in an age-related manner and deteriorate to the point where they are unable to be fertilized or do not mature. On the other end of the aging spectrum- in oocytes of very young women- quality of the oocytes is also not optimal. However, much less is known about the biological mechanisms that are impaired in these oocytes. The need to study this population of oocytes is growing due to the emergence of fertility preservation treatments for young cancer patients. For these patients, technologies that use extracted oocytes and their maturation in lab conditions have been developed. Previous work from our labs has shown that pre-pubertal oocytes do not mature in lab conditions as efficiently as in later ages. This proposed project aims to bring further understanding to the biological mechanisms impaired in pre-pubertal oocytes. Using our developed mouse model we will investigate the specific genetic pathways damaged in pre-pubertal oocytes, and examine if this damage can be repaired through the use if hormonal treatment of the oocytes in lab conditions. We will also test the possibility that the phenomena uncovered in mouse oocytes may be conserved in human oocytes. We will test the biological pathways discovered and our hormonal treatment regime in human pre-pubertal oocytes taken from procedures carried out on young cancer patients. The oocytes used in this project are usually discarded in clinical settings and patient consent is obtained before each use. The described collaboration between American and Israeli researchers will enable better understanding of why pre-pubertal oocytes do not mature well in-vitro, and may offer solutions on improving the quality of these oocytes for cancer patients.