The Impact of Histone Modifications in Endometriosis Highlights New Therapeutic Opportunities

Abstract

Endometriosis is a chronic disorder of the female reproductive system which afflicts a great number of women worldwide. Histone deacetylases (HDACs) prevent the relaxation of chromatin, thereby positively or negatively modulating gene transcription. The current review aims at studying the impact of histone modifications and their therapeutic targeting in endometriosis. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The current manuscript represents the most comprehensive, up-to-date review of the literature focusing on the particular role of HDACs and their inhibitors in the context of endometriosis. HDAC1, HDAC2, HDAC3, Sirtuin 1, and Sirtuin 3, are the five most studied HDAC enzymes which seem to, at least partly, influence the pathophysiology of endometriosis. Both well-established and novel HDACIs could possibly represent modern, efficacious anti-endometriotic drug agents. Altogether, histone modifications and their therapeutic targeting have been proven to have a strong impact on endometriosis.

Nuclear Expression of Phosphohistone H3 and Vitamin D Receptor – New Potential Markers in Diagnosis and Treatment of Endometriosis

“…There are limited data about PHH3, a protein thought to play a role in a number of biological processes related to endometriosis. The PHH3 protein, which is known to be involved in DNA-templated reactions to the nucleosome, is thought to undergo several genetic alterations over the course of this disease's development and progression [2,18].…”

“…Specific histone-modifying enzymes have also been linked to the onset and development of endometriotic lesions, in addition to these chemical global changes in histone structure [14,18]. Gujral et al's study, for instance, discovered that deacetylating the histone through HDAC3 enhanced the progression of endometriosis by controlling the expression of genes linked to inflammation and angiogenesis [17].…”

“…Overall, these studies have thoroughly examined the consequences of this protein alteration that may play a part in the pathogenesis of endometriosis, even though the precise role of PHH3 in this disease is still not yet entirely fully understood [14][15][16][17][18][19]. To better comprehend all of the mechanisms and to pinpoint further treatment strategies, additional research is required.…”

The role of peroxisome proliferator-activated receptors in endometriosis

“…Laparoscopic excision and thermal destruction of endometrial lesions are the most widely spread surgical treatments when pharmacological therapy fails to work or the disease course is complicated ( 16 ). Both retrograde menstruation and coelomic metaplasia are the two most common pathogenetic hypotheses, but the exact pathophysiology of endometriosis development and progression are still not fully explored ( 17 , 18 ). The hematogenous/lymphatic spread theory, the embryogenetic theory, and the stem cell recruitment theory are additional pertinent hypotheses ( 17 ).…”

Vitamin D and Mitosis Evaluation in Endometriosis: A Step toward Discovering the Connection?

“…In another study, PHH3 was discovered to be hypermethylated in ectopic endometriotic lesions. This may be a factor in the development of well-known endometriosis characteristics, such as altered gene expression and cellular function [ 16 , 17 , 18 , 19 ]. Gujral et al’s study, for instance, discovered that deacetylating histone through HDAC3 enhanced the progression of endometriosis by controlling the expression of genes linked to inflammation and angiogenesis [ 18 ].…”