No abstract

This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (no. 20591920 to K.N. and no. 23592407 to H.N.) and The Uehara Memorial Foundation (to K.N.).

Endometriosis, a common, benign, estrogen-dependent disease affecting 3-10% of women of reproductive age, is characterized by the ectopic growth of endometrial tissue that is found primarily in the peritoneum, ovaries and rectovaginal septum. Recently, endometriosis has been alternatively described as an immune disease, a genetic disease and a disease caused by exposure to environmental factors, in addition to its usual description as a hormonal disease. In addition, accumulating evidence suggests that various epigenetic aberrations play definite roles in the pathogenesis of endometriosis. Epigenetic alterations reported to date in endometriosis include the genomic DNA methylation of progesterone receptor-B, E-cadherin, homeobox A10, estrogen receptor-β, steroidogenic factor-1 and aromatase. Aberrant expression of DNA methyltransferases, which attach a methyl group to the 5-carbon position of cytosine bases in the CpG island of the promoter region and silence the corresponding gene expression, has also been demonstrated in endometriosis. This review summarizes the recent studies on the aberrant DNA methylation status and aberrant expression of DNA methyltransferases, which regulate DNA methylation, in endometriosis. We also discuss the recent information on the diagnostic and therapeutic implications of epigenetic alterations occurring in endometriosis.

The present findings demonstrated that aberrant histone modifications are present in endometriosis and that HDACIs reactivated epigenetically silenced genes, resulting in the suppression of cell proliferation, induction of cell cycle arrest and apoptosis of ECSCs. HDACIs are therefore promising agents for the treatment of endometriosis.

This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (no. 13237327 to K.N., no. 26861335 to K.K. and no. 23592407 to H.N.) and the Kanzawa Medical Research Foundation (to K.K.). There are no conflicts of interest to declare.