Altered Gene Expression in Endometrium of Endometriosis Patients May Hint at Disease Pathways

Altered Gene Expression in Endometrium of Endometriosis Patients May Hint at Disease Pathways

Women with advanced endometriosis have alterations in their endometrium’s gene expression compared to healthy controls — a discovery that may provide hints to the mechanisms underlying the disease.

The study, “DNA Microarray Analysis of Gene Expression in Eutopic Endometrium from Patients with Endometriosis,” appeared in the journal Advances in Reproductive Sciences.

In it, authors analyzed the expression of genes — using a technique called DNA microarray — in the endometrial tissues of five patients with advanced-stage endometriosis. They compared it to five controls without endometriosis who underwent an endometrial tissue biopsy at the late secretory phase of the menstrual cycle.

The analysis detected a total of 18,633 genes, of which 462 showed a higher expression (meaning that these genes were more active) and 643 a lower expression in endometriosis patients than in controls.

Authors performed a deeper analysis of the genes that increased expression by 1.5 times or more in the endometrium tissues of female patients, in order to understand which processes they might regulate.

They identified a cluster of genes linked to the immune system, positive regulation of cell motion and angiogenesis (blood vessel formation), for example. One of the genes identified as up-regulated was the one coding for matrix metalloproteinase 10 (MMP10). This protein disrupts normal endometrium tissue.

The researchers also found that expression of the MMP-1 and ICAM-1 genes was higher in late secretory stage endometrium in endometriosis patients.

ICAM-1 reduces the activity of a class of immune cells, called natural killer cells, suggesting that endometriosis formation is possibly linked to lower immune surveillance. Another pathway that might contribute to endometriosis is inflammation, as several genes related to cytokine production were also deregulated in endometriosis patients.

The genes that showed a decrease in expression were mostly linked to metabolic processes. One of these is called glutathione S-transferase M5 (GSTM5) and codes an enzyme with the same name.

“This enzyme removes toxic materials (…) and this could be significant, as there is a possibility that dioxin levels are connected to endometriosis,” they wrote. Dioxins are mainly byproducts of industrial practices and are known to be toxic to the environment.

Overall, these results suggest that gene expression in the endometrium from patients with advanced-stage endometriosis is different from the tissue of control subjects without endometriosis.

“The confirmation of the existence of pathophysiologically [disease causing] meaningful genes in patients with endometriosis through microarray analysis both broadens our understanding of the pathogenesis [disease progress] of endometriosis and assists the development of noninvasive diagnosis techniques and new approaches to therapy,” the study concluded.