These data support the notion that Cyclin D1 is involved in the differentiation of gonocytes and/or the proliferation of spermatogonia and afford proof of principle that differential miRNA expression may be a key regulator of these important processes. In our study of differentially expressed miRNA all the significantly down-regulated miRNA molecules i.e. miR-293, 291a-5p, 290-5p and 294* belong to the Y-27632 dihydrochloride miR-290-295 cluster and have previously been found to be highly enriched in the germ cell population of day 6 testis when compared to the somatic cell population. Additionally, the miR-290-295 cluster is highly expressed in mouse embryonic stem cells, with a role in promoting cell proliferation and maintaining pluripotency. This cluster is a target of pluripotency factors, and in turn targets the pluripotency factors OCT4, SOX2 and NANOG. The artificial expression of members of the miR-290 cluster restores the proliferation potential of ES cells lacking members of the miRNA processing machinery. These ES cells have a tendency to stall in the G1 stage of the cell cycle. More recently the miR-290 cluster has been found to have a pro-survival role by directly targeting pro-apoptosis genes, Caspase2 and Ei24 for mRNA degradation. The expression of the miR-290 cluster is high in multipotent adult germ cells, which are established upon culture of spermatogonial stem cells under ES cell conditions. We propose that the elevated expression of the miR-290 cluster maintains the expression of the pluripotency factor OCT4, and promotes the expression of early germ cell specific proteins in these cells for an extended period when compared to ES cells stimulated to differentiate. Additionally, knockout of the miR-290 cluster, MK-1775 side effects besides inducing a partially penetrant embryonic lethality, leads to the defective migration of primordial germ cells to the genital ridges during development, resulting in reduced germ cell numbers in the nascent gonads. Male germ cells recovered their numbers by mitotic proliferation while female germ cells were unable to do this causing infertility in the surviving female knockouts. The reduction in the expression of the members of the miR-290 cluster in our spermatogonial analysis, we believe, indicates that these cells have initiated the process of differentiation i.e. spermatogenesis. In contrast, little is known about the three miRNAs up-regulated in spermatogonia and their role in germ cell development remains unclear. The miR-136 has been found to be highly expressed in placental tissue as well as overexpressed in lung cancer, however knockdown has no effect on tumour growth, and its function has still not been elucidated. Conversely miR-743a has been identified to play a role in the oxidative stress response in mitochondria.