• PMID: 25329700
• Gene Name: MIR34A
• Condition: Oligoasthenoteratozoospermia and infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Oligoasthenoteratozoospermia and infertility

Oligoasthenoteratozoospermia and infertility in mice deficient for miR-34b/c and miR-449 loci

Comazzetto S, Di Giacomo M, Rasmussen KD, Much C, Azzi C, Perlas E, Morgan M, O'Carroll D.

Male fertility requires the continuous production of high quality motile spermatozoa in abundance. Alterations in all three metrics cause oligoasthenoteratozoospermia, the leading cause of human sub/infertility. Post-mitotic spermatogenesis inclusive of several meiotic stages and spermiogenesis (terminal spermatozoa differentiation) are transcriptionally inert, indicating the potential importance for the post-transcriptional microRNA (miRNA) gene-silencing pathway therein. We found the expression of miRNA generating enzyme Dicer within spermatogenesis peaks in meiosis with critical functions in spermatogenesis. In an expression screen we identified two miRNA loci of the miR-34 family (miR-34b/c and miR-449) that are specifically and highly expressed in post-mitotic male germ cells. A reduction in several miRNAs inclusive of miR-34b/c in spermatozoa has been causally associated with reduced fertility in humans. We found that deletion of both miR34b/c and miR-449 loci resulted in oligoasthenoteratozoospermia in mice. MiR-34bc/449-deficiency impairs both meiosis and the final stages of spermatozoa maturation. Analysis of miR-34bc-/-;449-/- pachytene spermatocytes revealed a small cohort of genes deregulated that were highly enriched for miR-34 family target genes. Our results identify the miR-34 family as the first functionally important miRNAs for spermatogenesis whose deregulation is causal to oligoasthenoteratozoospermia and infertility. FAU - Comazzetto, Stefano AU - Comazzetto S AD - European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo, Italy. FAU - Di Giacomo, Monica AU - Di Giacomo M AD - European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo, Italy. FAU - Rasmussen, Kasper Dindler AU - Rasmussen KD AD - European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo, Italy. FAU - Much, Christian AU - Much C AD - European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo, Italy. FAU - Azzi, Chiara AU - Azzi C AD - European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo, Italy. FAU - Perlas, Emerald AU - Perlas E AD - European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo, Italy. FAU - Morgan, Marcos AU - Morgan M AD - European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Monterotondo Scalo, Italy.