A comparative profile of the microRNA in Spermatogonial stem cells and male Infertility

Background: Infertility has been considered as a major widespread public health issue. Currently, almost 50% of infertility cases are due to male factors, including semen disorders, obstructions, cryptorchidism, varicocele and testicular failures, which can occur due to malfunctions in both somatic and germ cells. More than a thousand of protein coding genes that are involved in the spermatogenesis have been identified. Different miRNAs have been emerged as biomarkers for the diagnosis of male infertility such as Sertoli cell-only syndrome, mixed atrophy, and germ cell arrest. Spermatogonial stem cells (SSCs) are a subset of undifferentiated spermatogonia that are capable of self-renewal to maintain the pool of SSCs or give rise to spermatogenic lineage, thus supporting the continuous production of spermatozoa. Recent investigation disclosed that small ncRNAs, including miRNAs and piRNAs, are expressed in male germ cells and are important for spermatogenesis. MiRNAs conduce maintenance of the pool of SSCs. It has been shown that miR-20 along with miR-21, −34c, −135a, −146a, −182, −183, −204, −465a-3p, −465b-3p, −465c-3p, −465c-5p and −544 were preferentially expressed in the SSC-enriched population. Moreover, miR-544 regulates self-renewal of goat SSCs by targeting the promyelocytic leukemia zinc finger gene (PLZF), which is the first transcription factor to be identified as being involved in SSC self-renewal. Mir-RNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators (like p53 family member) and RNA binding proteins (Rbfox2, Cpeb1) in the mouse. MiR-202 played a role in maintaining the stem cell pool of SSCs by blocking their premature differentiation, which is typical of faster cell cycle and increased apoptosis. The fate of SSCs is tightly regulated by many paracrine and autocrine factors. In recent years, it has become clear that serval types of ncRNAs, involving miRNA, lncRNA, piRNA, small nucleolar RNA, and circRNAs, play important roles in stem cell self‐renewal by forming complicated epigenetic regulatory networks together with other epigenetic factors related to DNA methylation, histone methylation, and acetylation. We believe that more and more ncRNAs related to SSC self‐renewal will be discovered and functionally characterized, it will provide us a deeper insight into spermatogenesis and male infertility and pave a theoretical ground for applications in preservation and restoration of male fertility.

Keywords:

Infertility , SSC , miRNA