Determination of the expression status of histone methyltransferases in mouse ovarian tissues

Objective: Histone methylation is a process of adding methyl groups commonly to lysine and arginine residues of histone tails and is performed by histone methyltransferase enzymes (HMTs). Histone methylation is one of the critical epigenetic mechanisms, which is critically important for mammalian oocyte and follicle development. The aim of this study is to determine the expression patterns of histone methyltransferase genes in mouse ovarian tissues at different postnatal ages. Method: Four groups were created from female mice at the different ages of postnatal life as following: young (prepuberty, 3-week-old; n=6), adult (puberty, 7-week-old; n=7), late adult (postpuberty, 18-week-old; n=7) and aged (52-, and 60-week-old; n=7 from each week). In the mouse ovarian tissues, mRNA levels of Setd1b, Setd2, Cxxc1, and Setdb1 genes were determined by qRT-PCR, and their protein levels were detected by immunohistochemistry. The obtained data were evaluated statistically by using one-way ANOVA test. Results: Setd1b mRNA level in the aged group showed a significant decrease compared to the adult and late adult groups (P<0.001). Also, the Setd2 level exhibited a remarkable reduction in late adult and aged groups (P<0.05). While there were no differences for the Cxxc1 mRNA levels, the Setdb1 mRNA level increased gradually from the young to the aged groups (P<0.05). The SETD1B protein level displayed a notable decrease from the young group to the aged groups (P<0.01). There was a remarkable decrease for the CFP1 protein from the young to the aged groups (P<0.01). The SETD2 protein at highest level in the adult group decreased significantly toward the aged group (P<0.001). However, the SETDB1 protein levels gradually decreased from the young to the aged groups (P<0.01). Conclusion: We think that the expressional changes of Setd1b, Setd2, Cxxc1, and Setdb1 genes in the aging ovaries may have an impact on fertility loss accompanying biological aging. More detailed studies are required related to the reasons for the changed expression of these genes to elucidate the molecular mechanisms of fertility loss emerging with aging. Key words: histone methylation, oocyte, follicle, aging, fertility