Regulation of the transition from gonocytes to spermatogonia

In the western world there has been a significant decline in male reproductive health over the last 100 years, e.g. decreased sperm production and function and increased male infertility. Along with these more subtle changes the incidence of defects of reproductive development, including undescended testis and testicular germ cell cancer (seminoma and non-­‐seminoma), have increased. Seminoma and non-­‐seminoma are now the most common malignancy observed in young men. Both seminoma and non-­‐seminoma develop from the pre-­‐invasive lesion Carcinoma in Situ (CIS). The origin of CIS cells is still under debate however CIS cells are believed to result from improperly differentiated primordial germ cells (PGCs) or gonocytes. In general CIS cells express remarkably similar transcriptomes to gonocytes. Therefore it is essential to understand the cellular transition between gonocytes to spermatogonia to gain a better understanding of the aetiology of testicular germ cell tumours. MicroRNA (miRNA) are important regulators of posttranscriptional gene expression and have been identified as essential for embryogenesis, primordial germ cell differentiation and spermatogenesis. The aberrant expression of miRNA molecules is associated with male infertility and tumourigenesis including that of testicular germ cell tumours. We therefore examined the change in miRNA expression between postnatal gonocytes and spermatogonia for insights into how miRNA expression could influence this essential developmental process. We identified seven differentially expressed miRNA molecules between gonocytes and spermatogonia. The down regulated miRNA (miR-­‐290.5p, 291a-­‐ 5p, 293 and 294*) all belong to the miR-­‐290 family, which is a key regulator of pluripotency as well as primordial germ cell survival and proliferation. The up-­‐ regulated miRNA (miR-­‐136, 463* and 743a) are not as well known however miR-­‐136 is thought to be a tumour suppressor and miR-­‐743a is involved in oxidative stress. Target prediction software identified an abundance of targets in both the PTEN and Wnt signalling pathways. Wnt signalling is known to help maintain the undifferentiated spermatogonial stem cell population promote