Aberrant expression of deoxyribonucleic acid methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis

Abstract

Objective: Since endometriosis is a persistent disease with substantial gene dysregulation, there must be cellular memory of some sort that constitutes a unique cell identity for endometriotic cells. Epigenetic regulation, especially through DNA methylation, is a flexible, yet stable, mechanism for maintaining such a cellular memory. The aim of this study was to determine gene expression levels of DNMT1, DNMT3A, and DNMT3B, the three genes coding for DNA methyltransferases that are responsible for methylation.

Design: Cross-sectional measurements of gene expression levels of DNMT1, DNMT3A, and DNMT3B on endometriotic tissue.

Setting: Academic.

Patient(s): Seventeen patients with laparoscopically confirmed endometriosis and 8 healthy women who underwent tubal sterilization who were free of endometriosis were recruited for the study.

Intervention(s): Epithelial cells were harvested from tissue samples by laser capture microdissection and messenger RNA abundance was measured by quantitative real-time reverse transcription-polymerase chain reaction.

Main outcome measure(s): The expression levels of these genes in epithelial cells from 13 ectopic endometrial tissue samples, 10 eutopic endometrial tissue samples taken from women with endometriosis, and 8 normal endometrial tissue samples from women without endometriosis.

Result(s): The genes DNMT1, DNMT3A, and DNMT3B were over-expressed in the ectopic endometrium as compared with normal control subjects or the eutopic endometrium of women with endometriosis, and their expression levels were correlated positively with each other.

Conclusion(s): The aberrant expression of these genes suggests that aberrant methylation may be rampant in endometriosis. This also provides a strong piece of evidence that endometriosis ultimately may be an epigenetic disease.