Aberrant expression pattern of gap junction connexins in endometriotic tissues

Abstract

The expression of gap junction connexins (Cx) in the female reproductive tract of rodents and in the human endometrium is highly regulated by steroid hormones. Here we have investigated the distribution and regulation properties of Cx43, Cx26 and Cx32 in the human ectopic endometrium of 41 patients, using immunohistochemistry. The biopsies were obtained during the early or late follicular phase (26 cases), during the corpus luteum phase (five cases) and after a 6 month treatment with a gonadotrophin-releasing hormone (GnRH) agonist (three cases) or progestin (seven cases). Aberrant expression of Cx43 was found in the epithelium of nearly all endometriotic glands whereas Cx26, typical for human uterine epithelium cells, was only detected in 18 cases; in 17 it was co-expressed with Cx43. The stromal compartment of the tissues did not express any connexins investigated. Staining for Cx32 was absent in all endometriotic tissues. Strong expression of Cx43 was correlated with a high serum value of 17 beta-oestradiol, whereas a strong expression of Cx26 was found with high values of progesterone mainly in patients after progestin treatment. The epithelium of endometriotic implants collected after GnRH agonist treatment expressed Cx26 and Cx43 only moderately. The patterns described demonstrate an aberrant connexin expression and a different hormonal regulation pattern in endometriotic tissues compared to the normal cyclic uterine endometrium, thus indicating a high dedifferentiation from the normal situation. However, endometriosis still remains a hormonally-dependent benign disease, and hence, can be treated hormonally.

Up-Regulation of Gap Junctional Intercellular Communication and Connexin43 Expression by Retinoic Acid in Human Endometrial Stromal Cells

“…Correspondingly, loss of cell-cell communication through inappropriate expression of Cxs may be responsible for dedifferentiation processes leading to tumorigenesis. A report by Regidor et al (28) has shown chronically decreased levels of Cx43 in endometriotic stromal cells, comparable in expression with their normal counterpart during the implantation window portion of the reproductive cycle (14). These and other results (29,30) suggest that Cx43 plays a key role in the maintenance of normal human endometrium and that its aberrant expression may be involved in the development or progression of endometriosis.…”

Expression of gap junction protein connexin32 in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma

“…17 The comparison of Cx expression among normal, benign, and malignant tissues has been reported in stomach, 18 lung, 19 breast, 20 prostate, 21 skin, 22 and endometrium. 23 Generally, Cx expression is lower in malignant tumors compared with normal tissues. Regarding liver tumors, several authors have evaluated GJIC and the immunohistochemistry of Cx in vivo, so far.…”

Physiological and pathological implications of retinoid action in the endometrium

“…Regidor et al (1997) showed that CX43 levels were reduced in human endometriosis lesions and this finding was confirmed by Yu et al (2014b). They reported nearly exclusive CX43 immunostaining in the stromal compartment of normal biopsies, with reduced immunostaining and redistribution to scattered epithelia in the eutopic endometria of women with endometriosis.…”