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

Abstract

Spermatogenesis is composed of three distinctive phases, which include self-renewal of spermatogonia via mitosis, spermatocytes undergoing meiosis I/II and post-meiotic development of haploid spermatids via spermiogenesis. Spermatogenesis also involves condensation of chromatin in the spermatid head before transformation of spermatids to spermatozoa. Epigenetic regulation refers to changes of heritably cellular and physiological traits not caused by modifications in the DNA sequences of the chromatin such as mutations. Major advances have been made in the epigenetic regulation of spermatogenesis. In this review, we address the roles and mechanisms of epigenetic regulators, with a focus on the role of microRNAs and DNA methylation during mitosis, meiosis and spermiogenesis. We also highlight issues that deserve attention for further investigation on the epigenetic regulation of spermatogenesis. More importantly, a thorough understanding of the epigenetic regulation in spermatogenesis will provide insightful information into the etiology of some unexplained infertility, offering new approaches for the treatment of male infertility.Reproduction (2015) 150 R25-R34

Establishment and applications of male germ cell and Sertoli cell lines

“…It is worth noting that this cell line can be cultured for 1.5 years and expanded with a significant increase of cell numbers, while maintaining high levels of PCNA and UCHL1. Moreover, this human SSC line is able to colonize and proliferate in the recipient mice (Hou et al 2015). Neither Y chromosome microdeletions of numerous genes nor tumor formation has been observed in human SSC line.…”

“…Molecular and cellular analyses reveal that this cell line expresses a number of human spermatogonial and SSC hallmarks, including VASA, DAZL, MAGEA4, GFRA1, RET, UCHL1, GPR125, PLZF and THY1 (Hou et al 2015), indicating that these cells are human SSCs in phenotype. It is worth noting that this cell line can be cultured for 1.5 years and expanded with a significant increase of cell numbers, while maintaining high levels of PCNA and UCHL1.…”

“…Most importantly, we have for the first time established a human SSC cell line by stably overexpressing human SV40 large T antigen (Hou et al 2015). Molecular and cellular analyses reveal that this cell line expresses a number of human spermatogonial and SSC hallmarks, including VASA, DAZL, MAGEA4, GFRA1, RET, UCHL1, GPR125, PLZF and THY1 (Hou et al 2015), indicating that these cells are human SSCs in phenotype.…”

“…For example, using spermatogonial stem cell line C18-4, we have successfully demonstrated that Nodal plays an essential role in promoting the self-renewal of mouse SSCs via Smad2/3 pathway and Pou5f1 activation (He et al 2009) and GDNF stimulates the proliferation and survival of mouse SSCs by activating Ras/ERK1/2 signaling pathway and transcription factor Fos (He et al 2008). In addition, we have shown that miRNA-133b is uninvolved in the regulation of the human SSCs using a human SSC line (Hou et al 2015) and it specifically enhances the proliferation of human Sertoli cells (Yao et al 2016). Sertoli cell lines, e.g.…”

“…Specifically, these cell lines can be employed for investigating gene regulation, signaling transduction pathways, and non-coding RNA (e.g. microRNA and lncRNA) and DNA methylation in controlling the selfrenewal and differentiation of male germ cells (Yao et al 2015). For example, using spermatogonial stem cell line C18-4, we have successfully demonstrated that Nodal plays an essential role in promoting the self-renewal of mouse SSCs via Smad2/3 pathway and Pou5f1 activation (He et al 2009) and GDNF stimulates the proliferation and survival of mouse SSCs by activating Ras/ERK1/2 signaling pathway and transcription factor Fos (He et al 2008).…”