title: A unique combination of male germ cell miRNAs coordinates gonocyte differentiation.
abstract: The last 100 years have seen a concerning decline in male reproductive health associated with decreased sperm production, sperm function and male fertility. Concomitantly, the incidence of defects in reproductive development, such as undescended testes, hypospadias and testicular cancer has increased. Indeed testicular cancer is now recognised as the most common malignancy in young men. Such cancers develop from the pre-invasive lesion Carcinoma in Situ (CIS), a dysfunctional precursor germ cell or gonocyte which has failed to successfully differentiate into a spermatogonium. It is therefore essential to understand the cellular transition from gonocytes to spermatogonia, in order to gain a better understanding of the aetiology of testicular germ cell tumours. MicroRNA (miRNA) are important regulators of gene expression in differentiation and development and thus highly likely to play a role in the differentiation of gonocytes. In this study we have examined the miRNA profiles of highly enriched populations of gonocytes and spermatogonia, using microarray technology. We identified seven differentially expressed miRNAs between gonocytes and spermatogonia (down-regulated: miR-293, 291a-5p, 290-5p and 294*, up-regulated: miR-136, 743a and 463*). Target prediction software identified many potential targets of several differentially expressed miRNA implicated in germ cell development, including members of the PTEN, and Wnt signalling pathways. These targets converge on the key downstream cell cycle regulator Cyclin D1, indicating that a unique combination of male germ cell miRNAs coordinate the differentiation and maintenance of pluripotency in germ cells.
authors.affiliation: ARC Centre of Excellence in Biotechnology and Development, Discipline of Biological Sciences, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Skye C
authors.initials: SC
authors.lastname: McIver
authors.forename: Simone J
authors.initials: SJ
authors.lastname: Stanger
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Santarelli
authors.forename: Shaun D
authors.initials: SD
authors.lastname: Roman
authors.forename: Brett
authors.initials: B
authors.lastname: Nixon
authors.forename: Eileen A
authors.initials: EA
authors.lastname: McLaughlin
mesh_terms: D000818:Animals; D019938:Cyclin D1 / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005854:Germ Cells / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013091:Spermatogenesis / Q000235:genetics*; D013093:Spermatogonia / Q000378:metabolism / Q000502:physiology*; D060449:Wnt Signaling Pathway
chemical_list: C530105:Ccnd1 protein, mouse; D035683:MicroRNAs; D019938:Cyclin D1; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse