Role of miR-34c microRNA in the late steps of spermatogenesis

Abstract

Spermatogenesis is a cyclic process in which diploid spermatogonia differentiate into haploid spermatozoa. This process is highly regulated, notably at the post-transcriptional level. MicroRNAs (miRNAs), single-stranded noncoding RNA molecules of about 20-25 nucleotides, are implicated in the regulation of many important biological pathways such as proliferation, apoptosis, and differentiation. We wondered whether miRNAs could play a role during spermatogenesis. The miRNA expression repertoire was tested in germ cells, and we present data showing that miR-34c was highly expressed only in these cells. Furthermore, our findings indicate that in male gonads, miR-34c expression is largely p53 independent in contrast to previous results showing a direct link in somatic cells between the miR-34 family and this tumor suppressor protein. In order to identify target genes involved in germinal lineage differentiation, we overexpressed miR-34c in HeLa cells, analyzed the transcriptome of these modified cells, and noticed a shift of the expression profile toward the germinal lineage. Recently, it has been shown that exogenous expression of Ddx4/Vasa in embryonic chicken stem cells (cESC) induces cESC reprogramming toward a germ cell fate. When we simultaneously expressed miR-34c in such cells, we could detect an up-regulation of germ cell-specific genes whereas the expression of other lineage specific markers remained unchanged. These data suggest that miR-34c could play a role by enhancing the germinal phenotype of cells already committed to this lineage.

Sperm-borne microRNA-34c is required for the first cleavage division in mouse

“…Six miRNAs (miR-34b, -34c, -99a, -214, -451, and -449) also were found in one-cell embryos but not in the oocytes or in embryos beyond the one-cell stage. MiR-34c was chosen for further study because it is highly expressed in the mouse round spermatids (14).…”

MicroRNAs and DNA methylation as epigenetic regulators of mitosis, meiosis and spermiogenesis

“…Interestingly, miR-34b and miR-34c have been found to resemble the 'seed' sequence of miR-449. Coincidentally, miR-34b and miR-34c exhibit a similar effect to that of miR-449 during the development of male germ cells and spermatogenesis (Bouhallier et al 2010, Bao et al 2012, Wu et al 2014. Individual deficiency in miR-34b/c or miR-449 appears to have no obvious effect; however, simultaneous inactivation of miR-34b/34c and miR-449 leads to mouse oligoasthenoteratozoospermia (Wu et al 2014), implicating that double or triple knockout approach of miRNAs is needed to obtain the phenotype for certain miRNAs.…”

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

“…Approximately one-third of human genes are regulated by miRNAs [179]. They are implicated in the regulation of many important biological pathways such as proliferation, apoptosis, and differentiation in various species, but a large number of them (about 68 %) show a tissue-specific expression [180]. They are expressed in various testicular cell populations as well as epididymis, indicating a critical role in the various steps of the highly organized process of spermatogenesis, sperm maturation and maintenance of male fertility.…”