Elevated Immunoreactivity against Class I Histone Deacetylases in Adenomyosis

Abstract

Background/Aims: Adenomyosis is a common condition with a poorly understood pathogenesis. Recent data suggest that it may be an epigenetic disease. This study investigated the expression and localization of class I histone deacetylases (HDACs) in women with and without adenomyosis. Methods: The ectopic and homologous eutopic endometrium of 50 women with adenomyosis and the endometrium of 18 age- and menstrual phase-matched women without adenomyosis were used for immunohistochemical analysis. Tissue sections were immunostained with HDAC1, -2, and -3. Microscopic evaluation to assess the presence and localization of HDAC1–3 throughout the menstrual cycle in both eutopic endometrial and endometriotic tissues of women with adenomyosis was performed and compared with the normal endometrium. Results: We found that, compared with the normal endometrium, immunoreactivity against HDAC1 and HDAC3 was higher in both the eutopic and the ectopic endometrium. Increased HDAC2 in the eutopic endometrium was found to be associated with the severity of dysmenorrhea. Conclusion: Given the potential wide-ranging effect of histone deacetylation on gene expression, these findings suggest that HDACs may be involved in adenomyosis. They also suggest the possibility that HDAC2 may be involved in dysmenorrhea and its severity and that HDACs may be potential therapeutic targets in adenomyosis.

The Epigenetics of Endometriosis

“…One recent study, however, found that an epithelial-like endometriotic cell line expresses class I HDAC1, HDAC2, HDAC3, and HADC6, and class II HDAC4 and HDAC5 [105]. We also found that class I HDAC1, HDAC2, and HDAC2 immunoreactivity is elevated in adenomyosis as compared with normal endometrium [212]. In fact, our study on a rat model of endometriosis indicates that HDAC2 is aberrantly expressed in ectopic endometrium [106].…”

The Expression of Histone Deacetylase 1, But Not Other Class I Histone Deacetylases, Is Significantly Increased in Endometriosis

“…8 Moreover, because of their important role in steroid hormone-dependent gene expression, class I HDACs are essential in the pathogenesis of endometriosis and adenomyosis, also called endometriosis uteri interna, which are two illnesses that share common properties. 19,20 However, HDAC-8 is expressed only in human tissues with smooth muscle differentiation. 21,22 The expression of HDAC-1 and -2 in endometriosis has also been investigated by Colón-Díaz et al 23 They found higher levels of HDAC-1 protein staining in endometriosis compared with control endometrium as well as slightly higher HDAC-2 levels in certain cases of endometriosis.…”

Epigallocatechin-3-Gallate Reduces Myometrial Infiltration, Uterine Hyperactivity, and Stress Levels and Alleviates Generalized Hyperalgesia in Mice Induced With Adenomyosis

“…16 In addition, we have recently shown aberrant immunoreactivity to DNA methyl transferase (DNMT)-1 and DNMT-3B and also to class I histone deacetylases (HDACs) in adenomyosis. 17,18 The EGCG has been shown to suppress DNMTs and decrease HDAC activity, resulting in the reactivation of methylation-silenced genes. 19,20 Thus, it is likely that EGCG might also reactivate PR-B in adenomyosis, resulting in PR-B reactivation and possibly diminished progesterone resistance.…”