Small RNA molecules in the regulation of spermatogenesis

Abstract

Small RNA molecules (small RNAs), including small interfering RNAs (siRNAs), microRNAs (miRNAs), and piwi-interacting RNAs (piRNAs), have recently emerged as important regulators of gene expression at the post-transcriptional or translation level. Significant progress has recently been made utilizing small RNAs in elucidating the molecular mechanisms regulating spermatogenesis. Spermatogenesis is a complex process that involves the division and eventual differentiation of spermatogonial stem cells into mature spermatozoa. The process of spermatogenesis is composed of several phases: mitotic proliferation of spermatogonia to produce spermatocytes; two meiotic divisions of spermatocytes to generate haploid round spermatids; and spermiogenesis, the final phase that involves the maturation of early-round spermatids into elongated mature spermatids. A number of miRNAs are expressed abundantly in male germ cells throughout spermatogenesis, while piRNAs are only present in pachytene spermatocytes and round spermatids. In this review, we first address the synthesis, mechanisms of action, and functions of siRNA, miRNA, and piRNA, and then we focus on the recent advancements in defining the small RNAs in the regulation of spermatogenesis. Concerns pertaining to the use of siRNAs in exploring spermatogenesis mechanisms and open questions in miRNAs and piRNAs in this field are highlighted. The potential applications of small RNAs to male contraception and treatment for male infertility and testicular cancer are also discussed.

Expressions of miR-15a and its target gene HSPA1B in the spermatozoa of patients with varicocele

“…Since first discovered in 1993, miRNAs have been implicated in various human regulatory pathways, including cell growth, proliferation, apoptosis, and differentiation and therefore participate in the process of development and diseases (He et al 2009). It has been estimated that miRNAs may regulate up to 30% of all genes in the human genome (Lewis et al 2005).…”

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

“…The roles of piRNAs in spermatogenesis are supported by the well-established functions of their partner, the Piwi proteins. Recent evidence indicates that the piwi subfamily proteins are essential for stem cell selfrenewal, the development of male germ cells and spermatogenesis [202]. For instance, spermatogenesis is arrested at the pachytene spermatocyte stage in Mili-knockout mice [203].…”

“…Furthermore, the small non-coding RNAs Nct1 and Nct2 have recently been suggested to be piRNA precursors and are expressed particularly in pachytene spermatocytes [206], which also points to a role of piRNAs in the regulation of the meiotic stage in spermatogenesis. Although, Nct1 and Nct2-deficient mice display a decrease in a small cluster of piRNAs located on chromosome 2, it does not affect mouse spermatogenesis or fertility, suggesting that those piRNAs located on chromosome 2 are necessary to maintain transposon silencing [202]. Thus, it is likely that piRNAs are potentially involved in regulating the processes of meiosis and post-meiosis of male germ cell development.…”

Transcription and post-transcriptional regulation of spermatogenesis

“…Translational regulation is extremely important in late-stage germ cells, as transcription has ceased, and thus it cannot contribute to regulatory control. Finally, the recent identification of noncoding regulatory RNAs in the testes (He et al 2009) has added yet another level of complexity to spermatogenesis. Clearly, we are a long way from unravelling the complex multi-layered molecular circuits that control germ cell development and function.…”