Endometriosis From an Epigenetic Lens

Endometriosis can be characterized by increased HOXA10 gene expression and epigenetic abnormalities.

Key Points

Highlights:

• The researchers analyzed HOXA10 gene expression in order to understand its relationship with key epigenetic features of a promoter region in the gene in the eutopic and ectopic endometrium of the women who suffer from endometriosis.

Importance:

• Researchers have yet to elucidate the pathophysiology of the disease and the reasons for its adverse effects on fertility.
• If researchers can better understand the mechanism of endometriosis and its link with infertility, then they can formulate better treatments and standards of care for the disease.

What’s done here?

• There were two groups in this study:
  • The control group (21 healthy fertile women who underwent diagnostic laparoscopic surgery for benign gynecological conditions, they did not have endometriosis); eutopic endometrium was collected in proliferative and secretory phases. 
  • The experimental group (36 patients with endometriosis), ectopic and eutopic endometrial tissues were collected during the proliferative and secretory phases.
• The RNA was extracted from the tissue and cDNA was synthesized. using real-time quantitative polymerase chain reaction (PCR) and chromatin immunoprecipitation techniques the epigenetic profile of HOX10 expression alterations were analyzed, then subjected to statistical analysis.

Key results:

• HOXA10 gene expression decreased in eutopic tissues biopsied during the secretory phase. Eutopic endometrium also had lower acetylation and higher H3K9 methylation; greater MeCP2 incorporation on the HOXA10 gene promoter.
• Ectopic endometriotic lesions collected during the secretory phase were found to have higher levels of H3K9ac, H3K27me3, and H3K4me3 in the promoter region of the HOXA10 gene whenever the HOXA10 gene was induced.
• The ectopic endometrium was also found to be different from the control subset in the proliferative phase. In that phase, the ectopic endometrium had higher levels of HOXA10, lower incorporation of MeCP2, and higher amounts of H3K4me3 in the promoter region.
• In short, researchers found that HOXA10 gene expression is abnormal in women with endometriosis. They also proved that epigenetics may play a role in the overall disease and its progression.

Limitations of the study:

• The authors list small sample size and heterogeneous samples as potential limitations in the study.  

Lay Summary

Samadieh et al. from the Royan Institute for Reproductive Biomedicine, recently published an article in Reproductive Sciences titled “Epigenetic Dynamics of HOXA10 Gene in Infertile Women With Endometriosis.” In this paper, the researchers wanted to observe HOXA10 gene expression in the eutopic and ectopic endometrium of women with endometriosis. They wanted to see how certain epigenetic marks, like MeCP2, which play a role in the regulatory region of gene promoter, affect HOXA10 gene expression.

The study had 2 groups, an experimental group with women with endometriosis and a control group with healthy women who have previously undergone diagnostic laparoscopic surgery for benign gynecological conditions, but these women do not have endometriosis. The researchers collected ectopic and eutopic endometrial tissues from the women in the experimental group and they collected endometrial biopsies from the women in the control group, in different menstrual phases. The epigenetic profile of the genes of interest with regards to the expression of the HOX10 gene were analyzed.

The results show that HOXA10 gene expression is less in eutopic tissues biopsied when the participant was in the secretory phase of the cycle. The tissues collected from these women also showed lower acetylation and higher methylation of H3K9. They also had greater MeCP2 incorporation at the gene promoter. Ectopic endometrium collected from the women with endometriosis during the secretory phase had more H3K9ac, H3K27me3, and H3K4me3 in the promoter region of the gene of interest. The same tissue collected from women with endometriosis during the proliferative phase was found to be different from the control group because there was more HOXA10 gene expression, less MeCP2 incorporation, and more H3K4me3 in the promoter region. Overall, this experiment proves that endometriosis could be characterized by aberrant HOXA10 gene expression. Additionally, the authors illuminate the role of epigenetics in the initiation and progression of endometriosis.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29592776