Altered expression of the DNA repair protein, N-methylpurine-DNA glycosylase (MPG) in human gonads

Abstract

BACKGROUND: The multifunctional mammalian MPG is responsible for a damaged DNA base in the nucleus. The DNA repair enzyme is transported from the cytoplasm to nucleus to repair the DNA base when it is damaged. If the enzyme does not work properly, the damaged DNA may lead to carcinogenesis, cell death, aging or infertility.

MATERIALS AND METHODS: This study was performed to determine mRNA expression and intracellular localization of the DNA repair protein, N-methylpurine-DNA glycosylase (MPG), in human ovary and testicular tissues, particularly in epithelial ovarian tumor and spermatogenic (maturation) arrest infertile patients, by RT-PCR and immunohistochemical staining using human MPG monoclonal antibody. RESULTS: MPG mRNA expression in epithelial ovarian tumor and spermatogenic arrest testis tissues was slightly higher than in normal ovarian and testicular tissues, respectively. The present study demonstrated new and unexpected patterns of cellular and subcellular localization of this enzyme. In a normal ovary, immunostaining for MPG was observed in the nucleus of oocyte, granulosa and stromal cells. MPG was stained mostly in the nucleus and faintly-stained in the cytoplasm of normal coelomic epithelium as well as in benign epithelial ovarian tumors. However, the MPG expression of the nucleus in malignant epithelial tumors, both serous and mucinous type, disappeared. The spermatocyte and Leydig cells in normal testis were immunostained only in the cytoplasm. The spermatocyte and Leydig cells in spermatogenic arrest testis tissues showed up both in the nucleus and cytoplasm. The subcellular localization of MPG in the tissues tested was heterogeneous, while the altered MPG expression was found in ovarian tumor and spermatogenic arrest testis.

CONCLUSION: These results suggest MPG's role in human gonadal tissues and raise the possibility that the altered mRNA level and intracellular localization could be associated with ovarian tumorigenesis and male infertility.