Alterations of mitochondrial dynamics in endometriosis

Genes that have roles in mitochondrial dynamics show changes between ectopic and eutopic endometrial stromal cells, study indicates

Key Points

Highlight

• Alterations in genes that take part in the mitochondrial dynamics in ectopic endometrial cells, make them more adaptive to the hypoxic and inflammatory environment.

Importance

• Mitochondrial dysfunction has been shown to be active in many diseases, however, there has been a lack of knowledge about endometriosis.

What’s done here

• The researchers aimed to find a link between the changes in mitochondrial gene dynamics and endometriosis.
• The gene profiles of ectopic and eutopic endometrial stromal cells (ESCs) from patients and controls were compared.
• After the isolation of endometrial stromal cells, various methods were used to analyze the gene profile of the mitochondria.

Key results

• Significantly lower mRNA and protein levels of mitochondrial-related genes were observed in ectopic endometrial stromal cells compared to both controls and eutopic samples.
• Some genes were upregulated in eutopic endometrium compared to control endometrium, and some others were downregulated in eutopic endometrium of endometriosis patients.
• In terms of mitochondrial mass, ectopic endometrial stromal cells showed a decrease in levels compared with controls.
• Morphologically, wider cristae width and narrower cristae junction were observed in ectopic endometrial stromal cells.

Lay Summary

Mitochondria are known as the batteries of the cell with the ATP that they produce through oxidative phosphorylation. Mitochondrial dynamics are important mechanisms for mitochondria to maintain their integrity by continuously undergoing changes. Mitochondrial fusion is the joining of two mitochondrial ends and fission is the division of one mitochondrion into two. The main genes that regulate these processes are dynamic-related protein-1, mitofusin1 and 2 , and optic atrophy-1 along with lysocardiolipin acyltransferase-1.

It is known that the imbalance in these mitochondrial dynamics causes certain diseases including cancer. With the aim of investigating the relationship between the alteration of mitochondrial gene dynamics and endometriosis, researchers led by Ye et al. from Hangzhou, China conducted a study and the results were published in a recent issue of the European Journal of Medical Research.

Ectopic endometrial tissues were collected from 51 patients with stage III-IV endometriosis, along with eutopic endometrium samples from 31 of these patients, and eutopic endometrium samples from 71 control subjects. Following the isolation of endometrial stromal cells, multiple methods were employed to assess the mitochondrial gene expression.

Ectopic ESCs displayed significantly lower mRNA and protein levels of some mitochondria-related genes compared to both controlled endometrial stromal cells and eutopic samples. In eutopic endometrium, some of the mitochondrial-related genes were also altered compared to control endometrium. The authors discuss that these findings can be partly explained by the increased oxidative stress and reactive oxygen species accumulation in endometriosis.

What is more, mitochondrial mass analysis revealed a decrease in ectopic endometrial stromal cells compared with controls as well as wider cristae width and narrower cristae junction width. As the authors explain, this results in increased oxidative injury and proliferation of ectopic endometrial stromal cells. No significant differences were observed between the groups regarding cell survival.

In conclusion, it is thought that these alterations in the adaptive responses of the cells make way for endometrial cells to improve their adhesiveness and pro-inflammatory state and adapt to the new environment.

Research Source: https://pubmed.ncbi.nlm.nih.gov/37393390/