O6-Methylguanine-DNA Methyltransferase Plays a Role in Endometriosis Development

O6-Methylguanine-DNA Methyltransferase (MGMT) expression is different depending on the location and stage of endometriosis, which may indicate a faulty DNA repair mechanism playing role in the endometriosis development.

Key Points

Highlights:

• This study analyzed O6-methylguanine-DNA methyltransferase (MGMT) expression and behavior in the cell nuclei and cytoplasm of cells.
• The researchers hoped to find a relationship between MGMT behavior and endometriosis disease severity.

Importance:

• MGMT could potentially be used a therapeutic source. Studies like this one will help researchers ascertain the function and potential uses of MGMT.
• Scientists must find target markers for endometriosis. Identifying target marks will lead to more efficient diagnosis and treatment of the disease.

What’s done here?

• There were 32 patients in this study. All of these participants had undergone surgical treatment for their external genital endometriosis.
• The researchers collected ovarian tissues that contained regions of endometriosis. They also got samples from the uterine cavity.
• The samples were fixed and embedded. Hematoxylin and eosin were used to stain the histological specimens.
• A clinical-and-morphological comparative analysis was conducted.
• For some of the participants, the researchers made a note of the stages of proliferation and the secretion of the menstrual cycle.
• Tissue sections were used for the immunohistochemical study. The researchers used monoclonal mouse antibodies, positive and negative controls, then visualized the locations where antibodies bind to antigens.
• MGMT expression was quantified using the optical density in the cell nuclei and cytoplasm of stromal and epithelial cells found within the participant’s eutopic and ectopic endometrium.
• Image analysis was conducted using the NIS Elements 3.2. Software.
• The results of the study were subject to statistical analysis.  

Key results:

• It was found that glandular and stromal cells nuclei and cytoplasm typically exhibited MGMT positive reactions. That being said, the reaction is dependent on the stage of endometriosis and the phase of the menstrual cycle.
• Eutopic endometrial tissue MGMT levels were highest during the in the proliferative phase in the nuclei of epithelial cells.
• During stages I and II, areas with endometriosis were found to have increased MGMT expression in the epithelial nuclei. MGMT expression in these same areas was found to decrease in stages III and IV.
• Endometriosis development was found to be associated with an increase of study parameters in the stromal cell nuclei and cytoplasm.
• Changes in MGMT expression can directly affect DNA reparation, which can subsequently play a role in endometriosis disease progression.

Limitations of the study:

• In this study, the researchers observe protein behavior in the laboratory; however, these proteins may behave differently when they are not in their natural environment compared to when they are in the organism itself.

Lay Summary

Shchegolev et al. recently published a paper in Bulletin of Experimental Biology and Medicine that explores the localization and behavior of O6-methylguanine-DNA methyltransferase, otherwise known as MGMT, a protein that repairs DNA and could potentially possess therapeutic properties. Their paper titled “Immunohistochemical Features of O6-Methylguanine-DNA Methyltransferase Expression during Ovarian Endometriosis” focuses on MGMT expression in different stages of endometriosis as well as the behavior and localization of MGMT within the cell, namely cytoplasmic or nuclear.

32 women with external genital endometriosis participated in this study. The researchers collected ovarian tissue samples and samples from the uterine cavity of these aforementioned participants. These samples were fixed, embedded and stained thus that a clinical-and-morphological comparative analysis could be conducted. The immunohistochemical portion of the study consisted of an extensive experimental process after which the researchers could visualize the locations where antibodies bind to antigens. They were also able to conduct positive and negative control assays to ensure the reactions proceeded correctly. The researchers quantified MGMT expression using optical density in different areas of the cell. A software was used for image analysis and the data from the entire process was subject to statistical analysis.

The results show that MGMT expression in the eutopic endometrial tissue is highest in the epithelial cell nuclei during the proliferative phase. Additionally, there was a noticeable increase in MGMT expression in the nuclei of the epithelial cell s of endometriosis plagued regions during stage I and stage II of the disease; however, there is a decrease of MGMT expression in these regions during stage III and IV. The researchers found that the progression of endometriosis is linked with an increase of study parameters in the nuclear and cytoplasmic regions of stromal cells. Overall, it can be concluded that the DNA reparation process, managed directly by MGMT, is impaired in certain cells in women with endometriosis. This faulty mechanism can subsequently affect the process of endometriosis development.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29308563