Organization of the Cytoskeleton in Ectopic Foci of the Endometrium with Rare Localization

Abstract

(1) Background: Endometriosis is a common pathology of the female reproductive system, often accompanied by pain and decreased fertility. However, its pathogenesis has not been sufficiently studied regarding the role of the cytoskeleton. In this study, we describe two clinical cases involving rare localization of extragenital endometriosis (umbilicus) and compare them with genital endometriosis of different localization (ovaries and uterus), as well as eutopic endometrium obtained with separate diagnostic curettage without confirmed pathology. (2) Methods: The relative content of actin and tubulin cytoskeleton proteins was determined by Western blotting, and the expression of genes encoding these proteins was determined by RT-PCR in the obtained intraoperative biopsies. The content of 5hmC was estimated by dot blot experiments, and the methylase/demethylase and acetylase/deacetylase contents were determined. (3) Results: The obtained results indicate that the content of the actin-binding protein alpha-actinin1 significantly increased (p < 0.05) in the groups with endometriosis, and this increase was most pronounced in patients with umbilical endometriosis. In addition, both the mRNA content of the ACTN1 gene and 5hmC content increased. It can be assumed that the increase in 5hmC is associated with a decrease in the TET3 demethylase content. Moreover, in the groups with extragenital endometriosis, alpha- and beta-tubulin content was decreased (p < 0.05) compared to the control levels. (4) Conclusions: In analyzing the results, further distance of ectopic endometrial foci from the eutopic localization may be associated with an increase in the content of alpha-actinin1, probably due to an increase in the expression of its gene and an increase in migration potential. In this case, a favorable prognosis can be explained by a decrease in tubulin content and, consequently, a decrease in the rate of cell division.

The Cellular Respiration of Endometrial Biopsies from Patients with Various Forms of Endometriosis

“…An increase in PKM can lead to its accumulation in the intercellular space and induce cell migration through p-Tyr42 RhoA-mediated superoxide generation [45], leading to the formation of extragenital lesions. In addition, the RhoAdependent pathway may also be involved in an increase in the expression of a number of cytoskeletal proteins associated with an increase in migration potential, which we observed depending on the distance from the site of eutopic localization [46]. The results we obtained in this study are fully consistent with data on a decrease in OXPHOS in human peritoneal mesothelial and endometrial cells of nonhuman primates with endometriosis [26,27] and a transition to aerobic glycolysis [24,39,47].…”

Role of Cyclins and Cytoskeletal Proteins in Endometriosis: Insights into Pathophysiology

“…This implies that as ectopic endometrial foci relocate from their typical sites, the α-actinin-1 [9] content may rise, potentially signaling the increased migratory capacity of these cells. Additionally, a favorable prognosis in endometriosis could be attributed to the decrease in tubulin content, indicating a reduced rate of cell division [146].…”