Alterations in Gene Activity May Explain Some Hallmarks of Endometriosis

Alterations in Gene Activity May Explain Some Hallmarks of Endometriosis

Researchers at the University of California have shown that women with endometriosis present an altered epigenetic response profile, an important process that regulates gene activity. This leads to deregulation of some genetic expression, which might explain endometriosis development and progression.

The study, “Aberrant Endometrial DNA Methylome and Associated Gene Expression in Women with Endometriosis,” was published in the journal Biology of Reproduction.

In women with endometriosis, the tissue of the uterine lining, called the endrometrium, grows abnormally outside the uterus. It is known that the endometrium in endometriosis patients is different from that of unaffected women, not only on the molecular level but also in terms of steroid hormone responses. Although it is unclear why these differences happen, alterations in epigenetic response profile have been implicated.

The epigenetic response is an important mechanism that controls gene activity without altering its gene sequence. This mechanism is conserved, presenting nearly the same profile within each tissue. When deregulated, the epigenetic response profile is changed, which may lead to tissue dysfunction.

DNA methylation is an example of this response, in which methyl groups are added to the DNA, altering its function.

Previous studies have showed that controlled modifications in epigenetic response profile can play a role in steroid hormone responses of normal endometrial tissue. This process can have major implications not only in the way tissues function during pregnancy and menstruation, but also in endometrial disorders.

To better understand the implication of epigenetic response in endometriosis, researchers investigated the epigenetic response profile and associated gene expression of the endometrium in three phases of the menstrual cycle (called proliferative, early secretory, and midsecretory) of women with severe endometriosis.

The researchers analyzed 17 endometrial tissue samples from patients with severe endometriosis and compared them to 16 samples of women without endometriosis.

The researchers showed that the epigenetic profile across the different phases of the mentrual cycle in women with endometriosis differs from that observed in the control group.

They reported that many of the abnormalities were present in the early and midsecretory phases, where progesterone levels peak. These results may help explain resistance to progesterone action in endometriosis, a hallmark of endometrial dysfunction.

The epigenetic profile abnormalities observed in the samples from women with endometriosis were detected mainly in regions responsible for the up- or down-regulation of genes expression. This observation can be of great importance since these regions are highly controlled, and aberrant epigenetic profiles can alter cellular and tissue functions.

Moreover, the epigenetic profile alterations identified were associated with modifications in gene expression. Some of the genes that were affected are relevant for endometrial function, as are genes involved in cell proliferation, inflammation, vessel formation, and steroid hormone response.

Still, the impact of these findings of DNA methylation differences in both gene expression regulation and disease development is limited without proper and more detailed functional studies.

The information gathered from this study showed that alterations in the epigenetic response profile and steroid hormone actions in the endometrium contribute to endometriosis development and progression.