A unique combination of male germ cell mirnas coordinates gonocyte differentiation

Skye C. McIver, Simone J. Stanger, Danielle M. Santarelli, Shaun D. Roman, Brett Nixon, Eileen A. McLaughlin

Research output: Contribution to journalArticle

53 Citations (Scopus)

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.

Original languageEnglish
Article numbere35553
Pages (from-to)1-16
Number of pages16
JournalPLoS One
Volume7
Issue number4
DOIs
Publication statusPublished - 20 Apr 2012
Externally publishedYes

Fingerprint

MicroRNAs
Spermatogonia
Germ Cells
spermatogonia
germ cells
Cells
Testicular Neoplasms
microRNA
neoplasms
Spermatozoa
spermatozoa
microarray technology
Hypospadias
Wnt Signaling Pathway
Cryptorchidism
Cyclin D1
male fertility
Reproductive Health
Carcinoma in Situ
cyclins

Cite this

McIver, S. C., Stanger, S. J., Santarelli, D. M., Roman, S. D., Nixon, B., & McLaughlin, E. A. (2012). A unique combination of male germ cell mirnas coordinates gonocyte differentiation. PLoS One, 7(4), 1-16. [e35553]. https://doi.org/10.1371/journal.pone.0035553
McIver, Skye C. ; Stanger, Simone J. ; Santarelli, Danielle M. ; Roman, Shaun D. ; Nixon, Brett ; McLaughlin, Eileen A. / A unique combination of male germ cell mirnas coordinates gonocyte differentiation. In: PLoS One. 2012 ; Vol. 7, No. 4. pp. 1-16.
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McIver, SC, Stanger, SJ, Santarelli, DM, Roman, SD, Nixon, B & McLaughlin, EA 2012, 'A unique combination of male germ cell mirnas coordinates gonocyte differentiation', PLoS One, vol. 7, no. 4, e35553, pp. 1-16. https://doi.org/10.1371/journal.pone.0035553

A unique combination of male germ cell mirnas coordinates gonocyte differentiation. / McIver, Skye C.; Stanger, Simone J.; Santarelli, Danielle M.; Roman, Shaun D.; Nixon, Brett; McLaughlin, Eileen A.

In: PLoS One, Vol. 7, No. 4, e35553, 20.04.2012, p. 1-16.

Research output: Contribution to journalArticle

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AU - Stanger, Simone J.

AU - Santarelli, Danielle M.

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AU - Nixon, Brett

AU - McLaughlin, Eileen A.

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McIver SC, Stanger SJ, Santarelli DM, Roman SD, Nixon B, McLaughlin EA. A unique combination of male germ cell mirnas coordinates gonocyte differentiation. PLoS One. 2012 Apr 20;7(4):1-16. e35553. https://doi.org/10.1371/journal.pone.0035553