Abstract
Background: Ion channels play a crucial role in many physiological processes. Several subtypes are expressed in the endometrium. Endometriosis is strictly correlated to estrogens and it is evident that expression and functionality of different ion channels are estrogen-dependent, fluctuating between the menstrual phases. However, their relationship with endometriosis is still unclear. Objective: To summarize the available literature data about the role of ion channels in the etiopathogenesis of endometriosis. Methods: A search on PubMed and Medline databases was performed from inception to November 2019. Results: Cystic fibrosis transmembrane conductance regulator (CFTR), transient receptor potentials (TRPs), aquaporins (AQPs), and chloride channel (ClC)-3 expression and activity were analyzed. CFTR expression changed during the menstrual phases and was enhanced in endometriosis samples; its overexpression promoted endometrial cell proliferation, migration, and invasion throughout nuclear factor kappa-light-chain-enhancer of activated B cells-urokinase plasminogen activator receptor (NFκB-uPAR) signaling pathway. No connection between TRPs and the pathogenesis of endometriosis was found. AQP5 activity was estrogen-increased and, through phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT), helped in vivo implantation of ectopic endometrium. In vitro, AQP9 participated in extracellular signal-regulated kinases/p38 mitogen-activated protein kinase (ERK/p38 MAPK) pathway and helped migration and invasion stimulating matrix metalloproteinase (MMP)2 and MMP9. ClC-3 was also overexpressed in ectopic endometrium and upregulated MMP9. Conclusion: Available evidence suggests a pivotal role of CFTR, AQPs, and ClC-3 in endometriosis etiopathogenesis. However, data obtained are not sufficient to establish a direct role of ion channels in the etiology of the disease. Further studies are needed to clarify this relationship.
Highlights
Endometriosis, defined as the presence of endometrial-like tissue outside the uterine cavity, is an estrogen-dependent benign disease that affects about 10% of reproductive-age women [1,2,3,4]
Several studies have addressed the presence and altered function of ion channels in both eutopic and ectopic endometrium [40,41,42,43], suggesting that their overexpression may play an important role in the pathogenesis of endometriosis [1,44,45,46,47]
We performed a literature search on the MEDLINE database for articles written in English and published from inception to November 2019, in order to assess the search question “Does a relation between ion channels and etiopathogenesis of endometriosis exist?” The following Medical Subject Headings (MeSH) terms were used to screen and identify studies: “Endometriosis” (Unique ID: D004715), “ion channels” (Unique ID: D007473), “etiology” (Unique ID: Q000209)
Summary
Endometriosis, defined as the presence of endometrial-like tissue outside the uterine cavity, is an estrogen-dependent benign disease that affects about 10% of reproductive-age women [1,2,3,4]. Several studies have addressed the presence and altered function of ion channels in both eutopic and ectopic endometrium [40,41,42,43], suggesting that their overexpression may play an important role in the pathogenesis of endometriosis [1,44,45,46,47]. Endometriosis is strictly correlated to estrogens and it is evident that expression and functionality of different ion channels are estrogen-dependent, fluctuating between the menstrual phases. CFTR expression changed during the menstrual phases and was enhanced in endometriosis samples; its overexpression promoted endometrial cell proliferation, migration, and invasion throughout nuclear factor kappa-light-chain-enhancer of activated B cells-urokinase plasminogen activator receptor (NFκB-uPAR) signaling pathway.
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