فایل ورد کامل نقش میکرو RNA ها در تنظیم اسپرماتوژنز پستانداران

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تعداد صفحات این فایل: ۲۰ صفحه

بخشی از مقاله انگلیسیعنوان انگلیسی:The roles of microRNAs in regulation of mammalian spermatogenesis~~en~~

Abstract

Mammalian spermatogenesis contains three continuous and organized processes, by which spermatogonia undergo mitosis and differentiate to spermatocytes, follow on meiosis to form haploid spermatids and ultimately transform into spermatozoa. These processes require an accurately, spatially and temporally regulated gene expression patterns. The microRNAs are a novel class of post-transcriptional regulators. Cumulating evidences have demonstrated that microRNAs are expressed in a cell-specific or stage-specific manner during spermatogenesis. In this review, we focus on the roles of microRNAs in spermatogenesis. We highlight that N6-methyladenosine (m6A) is involved in the biogenesis of microRNAs and miRNA regulates the m6A modification on mRNA, and that specific miRNAs have been exploited as potential biomarkers for the male factor infertility, which will provide insightful understanding of microRNA roles in spermatogenesis.

Introduction

Male fertility is dependent upon the successful perpetuation of spermatogenesis that is a highly organized process of germ cell differentiation occurring within the seminiferous tubules in the testes. Spermatogonial stem cells (SSCs) are a subset of undifferentiated spermatogonia that are capable of self-renewal to maintain the pool of SSCs or differentiation to give rise to spermatogenic lineage, thus supporting the continuous production of spermatozoa. Spermatogenesis initiates once SSCs enter differentiation process [1]. The spermatogonia go into the meiotic phase and become spermatocytes. After a long-lasting meiosis I, preleptotene spermatocytes transform into second spermatocytes and enter meiosis II to produce haploid round spermatids [2], which undergo spermiogenesis including acrosomal biogenesis, flagellum development, chromatin condensation, cytoplasmic reorganization and exclusion [3]. Ultimately, the round spermatids transform into spermatozoa, which are released into the lumen of seminiferous tubules [4].

This highly organized spermatogenesis requires accurate, spatial and temporal regulation of gene expression governed by transcriptional, post-transcriptional and epigenetic processes [5, 6]. More than a thousand of protein coding genes that are involved in the spermatogenesis have been identified [7, 8]. However, the mechanisms that mediate the expression of these spermatogenesis-related genes have not been fully uncovered. The microRNAs (miRNAs, miR), small (~22 nucleotides) single-strand noncoding RNAs, are linked to cell proliferation, differentiation and apoptosis [9–]. Transcriptome data indicate that miRNAs are extensively transcribed during spermatogenesis. The miRNAs are differentially expressed in a cellspecific and step-specific manner ([12, 13], Chen et al. unpublished data). Some miRNAs are specifically expressed in certain type of male germ cells, while the others are universally expressed among different types of cells in the testes. Growing evidences have showed that the miRNAs are essential for male germ cell development and differentiation [14–]. A few recent reviews have reported the roles of miRNAs in spermatogenesis and fertility [5, 6, 10, 11]. In this article, we briefly summarize the most recent progress of miRNAs in the regulation of spermatogenesis.

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