Abstract
Spermatogenesis is a complicated process including spermatogonial stem cells self-renewal and differentiates into mature spermatozoa. MicroRNAs (miRNAs) as a class of small non-coding RNAs play a crucial role during the process of spermatogenesis. However, the function of a plenty of miRNAs on spermatogenesis and the potential mechanisms remain largely unknown. Here, we show that genetically conditional overexpressed miR-10a in germ cells caused complete male sterility, characterized by meiotic arrested in germ cells. Analysis of miR-10a overexpression mouse testes reveals that failure of double strand break (DSB) repairs and aberrant spermatogonial differentiation. Furthermore, we identified Rad51 as a key target of miR-10a in germ cell by bioinformatics prediction and luciferase assay, which may be responsible for the infertility of the miR-10a overexpressed mice and germ cell arrested patients. Our data show that miR-10a dependent genetic regulation of meiotic process is crucial for male germ cell development and spermatogenesis in both mouse and human. These findings facilitate our understanding of the roles of miRNA-10a in spermatogenesis and male fertility.
Highlights
Mammalian spermatogenesis is a complex cellular differentiation process through which male germline stem cells develop sequentially into spermatogonia, spermatocytes, spermatids, and eventually spermatozoa
We found that the highest miR-10a expression levels were detected at postnatal day 7 (P7) testes, and displayed a gradually declining expression pattern from postnatal 7 (P7) to adult testes (P60; Figure 1A)
By immunolabeled testes at P7 with DDX4, PLZF, GATA4 and STRA8, we found that the numbers of DDX4-positive cells per Sertoli cells (GATA4 positive cells) were significantly decreased in sections of Ddx4-cOE testes compared with WT controls (Figure 3A)
Summary
Mammalian spermatogenesis is a complex cellular differentiation process through which male germline stem cells develop sequentially into spermatogonia, spermatocytes, spermatids, and eventually spermatozoa. This process can be divided into three phases based upon the major cellular events occurring, which called mitosis (spermatogonial proliferation and differentiation), meiosis (reduction of chromosomal number from diploid to haploid), and spermiogenesis (spermatid differentiation into spermatozoa; de Kretser et al, 1998). These cellular events require precise spatiotemporal expression of specific protein-coding genes, which are tightly controlled at both the transcriptional and post-transcriptional levels. Translational repression of mRNAs that are transcribed in spermatocytes and/or early spermatids must be achieved through a post-transcriptional regulatory mechanism, which still remains elusive
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