Age-dependent differential regulation of DNA methyltransferases in the mouse uterus

Uterine maturation is accompanied by substantial epigenetic remodeling in female reproductive tissues; however, the dynamics of DNA methylation during the transition from the prepubertal to the reproductively mature uterus remain poorly understood. In this study, we investigated age-dependent alterations in DNA methylation machinery in the mouse uterus by examining the expression of key DNA methyltransferases such as Dnmt1, Dnmt3a, Dnmt3b, and Dnmt3l, together with global DNA methylation levels. Protein expression was analyzed by Western blot analysis using whole uterine tissue, while tissue distribution and cellular localization were evaluated by immunohistochemistry. Our results demonstrate a significant reduction in the expression of all examined DNA methyltransferases in reproductively mature compared to prepubertal uterine tissue. Notably, the most pronounced differences were observed for Dnmt3b and Dnmt3l, suggesting alterations in de novo DNA methylation capacity during uterine maturation. In parallel, global DNA methylation levels, as indicated by 5-methylcytosine immunoreactivity, were significantly decreased in mature uterine tissue, indicating a shift in the epigenetic landscape associated with reproductive maturation. Collectively, these findings reveal coordinated changes in the DNA methylation machinery during uterine maturation and provide insight into epigenetic remodeling associated with the acquisition of reproductive competence.