Aberrant Immunoreactivity of Deoxyribonucleic Acid Methyltransferases in Adenomyosis

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DNA methyltransferase (DNMT) immunoreactivity differed between adenomyosis and normal endometrium, with higher DNMT1 and DNMT3B in ectopic sites and reduced DNMT3A, suggesting an epigenetic role in the disease.

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Abstract

OBJECTIVES: To investigate the expression and localization of deoxyribonucleic acid methyltransferases (DNMTs) in women with and without adenomyosis. STUDY DESIGN: Ectopic and homologous eutopic endometrium from 50 women with adenomyosis and endometrium from 18 age- and menstrual phase-matched women without adenomyosis were used for immunohistochemical analysis. Tissue sections were immunostained with DNMT1, DNMT3A, and DNMT3B. Microscopic evaluation to assess the presence and localization of DNMT1, DNMT3A, and DNMT3B throughout the menstrual cycle in both eutopic endometrial and endometriotic tissues of women with adenomyosis was performed, and comparison with normal endometrium was made. RESULTS: Compared with normal endometrium, immunoreactivity to DNMT1 and DNMT3B was higher in ectopic endometrium, while DNMT3A staining levels were significantly reduced in both eutopic and ectopic endometrium. DNMT1 immunoreactivity in eutopic endometrium was positively associated with heavier menses. Increased DNMT3B immunoreactivity in ectopic, but not eutopic, endometrium was associated with the severity of dysmenorrhea. CONCLUSIONS: The immunoreactivity to DNMTs in adenomyosis differs significantly from that in normal endometrium, suggesting that adenomyosis may be an epigenetic disease. The finding that DNMT3B correlates with the severity of dysmenorrhea suggests that DNMTs may be involved in adenomyosis-caused dysmenorrhea and its severity. Thus, therapeutics based on epigenetic rectification may hold promise in the management of adenomyosis.

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Condition tags

dysmenorrheaadenomyosis

MeSH descriptors

Adenomyosis Adenomyosis DNA (Cytosine-5-)-Methyltransferases DNA Methylation Adenomyosis Adenomyosis DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases DNA Methyltransferase 3A DNA Methyltransferase 3B Dysmenorrhea Dysmenorrhea Dysmenorrhea Endometrium Endometrium Epigenomics Female Humans Immunohistochemistry Middle Aged

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