Expression of DNA Methyltransferases in Human Endometrium in Relation to Menstrual Cycle and Abnormal Uterine Bleeding [145]

INTRODUCTION: The menstrual cycle is a sex steroid-driven process thought to be under the influence of multiple epigenetic modulators. DNA methytransferases (DNMT) appear to regulate gene activity during decidualization, but relative expression level by phase is not fully understood and has not been studied in abnormal uterine bleeding. METHODS: Immunohistochemistry was performed on tissue microarrays derived from 541 endometrial samples including secretory, proliferative, atrophic histopathologic diagnoses. Baseline demographic and clinical data were collected for all 541 study participants. The expression levels of DNMT1, DNMT3a, DNMT3b, estrogen receptor, and progesterone receptor were determined by staining scores, generated as the product of staining intensity and extent. Review was completed by a pathologist blinded to the clinical information. Statistical analysis of composite scores was performed using JMP 9.0. RESULTS: For each phase of the menstrual cycle, epithelial and stromal cell nuclei immunostained for DNMT1, DNMT3a, and DNMT3b. Although tissue levels of DNMT3a and DNMT3b by staining score were lower in the midsecretory phases as compared with the proliferative phase, levels of DNMT1 were increased in the midsecretory phase. Overall expression of DNMT1 was higher in abnormal uterine bleeding, whereas DNMT3A and DNMT3b were unchanged. CONCLUSION: Our study is the largest yet to compare DNMT expression in human endometrium at different stages of decidualization and in abnormal uterine bleeding. Our study provides confirmatory evidence that DNMTs are expressed in human endometrium in a phase-specific manner. Further evaluation of a putative role for DNMTs in menstruation is warranted.