Molecular alterations in endometriosis pathogenesisBy: Eylül GÜN - Nov 26, 2021
Molecular alterations may help to understand endometriosis better, and help find new diagnostic markers-treatment methods
- It is important to understand the underlying pathogenetic mechanisms of endometriosis well to develop new diagnostic markers and provide novel treatment methods.
- Helping patients in the diagnosis, symptom relief, and treatment for this multifactorial and complex disease, understanding its pathogenesis may be possible by new techniques for developing novel markers and therapeutic methods.
- The discovered molecular alterations in the endometriosis pathogenesis include changes in the carcinogenesis pathway, the inflammatory and immune system, and oxidative stress mechanisms.
- Extra-pelvic endometriosis is usually seen in patients with autoimmune disorders.
- Hormonal imbalances contribute to infertility and deep infiltrating endometriosis.
- The epithelial-mesenchymal transition of the endometrial cells is thought to be a promoting factor for the lesions to develop and invade the surrounding tissues.
- The recent developments in next-generation sequencing and epigenetic modulations provide pivotal information and can be used in creating new treatment methods.
- Various in-vitro and in-vivo study models are helpful in learning the etiopathogenesis and progression of the disease and may also be used to evaluate drug efficacy.
What’s done here:
- This is a review study from India combining the results of all the studies conducted to reveal the underlying pathogenetic mechanisms of endometriosis.
- It was aimed to help understand disease etiology and progression and provide better solutions for the patients.
Endometriosis has been in our lives for decades, however little is known about its pathogenesis making it hard to diagnose and manage. A review study conducted by Balasubramanian et al. from India reveals all the characteristics and the underlying conditions in the pathogenesis of endometriosis from a wide angle aiming to help understand the problem better and find new therapeutic targets. The article was recently published in the journal Cellular Signaling.
The authors talk briefly about the incidence, pathophysiology, suggested theories, radiological findings, and staging of endometriosis and move on to the known molecular alterations underlying its pathogenesis. These dysregulations are grouped under some categories depending on the pathways they act upon. Most of the altered genes in endometriosis pathogenesis have a role in the carcinogenesis pathway (PTEN, KRAS, TP53, ARID1A, etc), stimulating cell proliferation, adhesion, and altering apoptosis. Transcription factors and cell-cycle regulators also play major roles.
Endometriosis has an inflammatory nature therefore another affected pathway is the immune response pathway. The cells that have a role in inflammation (macrophages, dendritic cells, NK cells, mast cells, and leukocytes) and pro-inflammatory cytokines are all activated causing the body to create both an immunologic response and an autoimmune-like response. Hormonal disbalance is seen as estrogen dependence and progesterone resistance in endometriosis and may result in infertility and may be the cause of deep infiltrating endometriosis. Treatment with hormonal agents is shown to be effective.
The role of oxidative stress and reactive oxygen species in promoting inflammation, angiogenesis, and cell survival in endometriosis is also important. MicroRNAs have recently been shown to activate the key regulators of oxidative stress, therefore, inducing the pro-inflammatory pathways in the pathogenesis. With the help of a hypoxic environment and estrogen dominance, epithelial endometrial cells turn into mesenchymal cells. This process helps the endometriotic lesions to develop and invade into other tissues. Last but not least, the authors provide information about the epigenetic alterations that surround the pathogenesis of endometriosis. With the recent development Genome-Wide Association Studies, a lot has been surfaced about these mechanisms which provide clues for new and alternative treatment methods.
The authors also list the available techniques to create in-vitro and in-vivo study models to evaluate the aforementioned molecular alterations. They conclude by saying that understanding the disease pathophysiology and all the alterations that surround it is crucial in developing new diagnostic markers and therapeutic agents.
Research Source: https://pubmed.ncbi.nlm.nih.gov/34464692/
endometriosis molecular alterations pathogenesis bioinformatics microarray cell survival transcription carcinogenesis apoptosis inflammation hormones