Ion channels in the endometrium: Regulation of endometrial receptivity and embryo implantation

Background: Although embryo implantation is a prerequisite for human reproduction, it remains a poorly understood process. The molecular mechanisms regulating endometrial receptivity and/or embryo implantation are still largely unclear. Methods: Pubmed and Medline literature databases were searched for articles in English published up to December 2013 with relevant keywords including 'endometrium', 'Na+, Cl-, K+, or Ca2+channels', 'ion channels', 'endometrial receptivity', 'blastocyst implantation' and 'embryo implantation'. Results: At the time of writing, more than 14 types of ion channels, including the cystic fibrosis transmembrane conductance regulator, epithelial sodium channel and various Ca2+and K+channels, had been reported to be expressed in the endometrium or cells of endometrial origin. In vitro and/or in vivo studies conducted on different species, including rodents, pigs and humans, demonstrated the involvement of various ion channels in the process of embryo implantation by regulating: (i) uterine luminal fluid volume; (ii) decidualization; and (iii) the expression of the genes associated with implantation. Importantly, abnormal ion channel expression was found to be associated with implantation failure in IVF patients. Conclusions: Ion channels in the endometrium are emerging as important players in regulating endometrial receptivity and embryo implantation. Abnormal expression or function of ion channels in the endometrium may lead to impaired endometrial receptivity and/or implantation failure. Further investigation into the roles of endometrial ion channels may provide a better understanding of the complex process of embryo implantation and thus reveal novel targets for diagnosis and treatment of implantation failure.