Role of deoxyribonucleic acid polymerase ε in spermatogenesis in mice

Previous studies on DNA polymerase ε indicate that this enzyme is involved in replication of chromosomal DNA. In this study, we examined the expression of DNA polymerases α, δ, and ε during mouse testis development and germ cell differentiation. The steady-state levels of mRNAs encoding DNA polymerase ε and the recombination enzyme Rad51 remained constant during testis development, whereas the mRNA levels of DNA polymerases α and δ declined from birth until sexual maturity. Immunohistochemical staining methods, using a stage-specific model of the seminiferous epithelium, revealed dramatic differences between DNA polymerase α and ε distribution. As expected, DNA polymerase α and proliferating cell nuclear antigen showed relatively strong immunostaining in mitotically proliferating spermatogonia and even stronger staining in preleptotene cells undergoing meiotic DNA replication. The distribution of Rad51 was similar, but there was a dramatic peak in late pachytene cells. In contrast, DNA polymerase ε was detectable in mitotically proliferating spermatogonia but not in the early stages of meiotic prophase. However, DNA polymerase ε reappeared in late pachytene cells and remained through the two meiotic divisions, and was present in haploid spermatids up to the stage at which the flagellum starts developing. Overall, the results suggest that DNA polymerase ε functions in mitotic replication, in the completion of recombination in late pachytene cells, and in repair of DNA damage in round spermatids. In contrast, DNA polymerases α and δ appear to be involved in meiotic DNA synthesis, which occurs early in meiotic prophase, in addition to functioning in DNA replication in proliferating spermatogonia.