Abnormally up-regulated cystic fibrosis transmembrane conductance regulator expression and uterine fluid accumulation contribute to Chlamydia trachomatis-induced female infertility

Abnormally enhanced cystic fibrosis transmembrane conductance regulator-mediated apoptosis in endometrial cells contributes to impaired embryo implantation in controlled ovarian hyperstimulation

“…To further verify the effect of COH on the expression of CFTR in endometrium, we determined the expression of CFTR in primary culture of mice endometrial epithelial cells from both control and COH-treated animals with the presence or absence of blastocyst. As shown in Figure 2B, the CFTR expression was very low and predominantly detected in the membrane of endometrial epithelial cells 4 days after mating, which is consistent with our previous findings showing extremely low CFTR expression at the diestrus stage (15,19). In contrast, the expression of CFTR was dramatically increased in COH-treated endometrial cells on the same day (Fig.…”

“…The CFTR, a cAMP-dependent anion channel, has been demonstrated to be regulated by E through the different stages of the estrous cycle (15,19). Of note, down-regulated CFTR expression during preimplantation has been observed in endometrial epithelia of mice (17), providing a molecular basis for the ''closure'' of the uterine lumen that occurred on the day of implantation.…”

“…In addition to its wellestablished ion channel function, CFTR has been proposed to have many other roles that either directly or indirectly impact various cellular functions, including apoptosis (13,14). Previous studies from both our laboratory and that of other investigators have revealed that the expression of uterine CFTR changes with the estrous cycle (15)(16)(17)(18)(19). In addition, stimulation of CFTR expression by estrogen (E) both in vivo and in vitro (20,21) has also been demonstrated and down-regulation of CFTR by P reported (22).…”

“…In addition, stimulation of CFTR expression by estrogen (E) both in vivo and in vitro (20,21) has also been demonstrated and down-regulation of CFTR by P reported (22). The ovarian hormone-dependent regulation of CFTR expression provides a physiologic basis for the cyclic change in fluid volume (19); however, the question as to whether CFTR participates in the supraphysiologic E 2 -induced effects on embryo development as well as the endometrium has never been investigated. In the present study, we hypothesized that supraphysiologic E 2 during COH may lead to abnormal up-regulation of CFTR expression and thus increased apoptosis in the endometrium, which results in impaired endometrial receptivity and subsequent implantation failure.…”

Chlamydia trachomatis Infection and Reproductive Health Outcomes in Women

“…Moreover, CFTR expression has another effect on fertility in the uterus, given that this substance plays a role in the regulation of the balance between the fluid volume in the endometrial mucous membrane during the estrous cycle, which is involved in blastocyst implantation. In the murine model, CFTR overexpression induced by cytokine release during C. trachomatis infection leads to abnormal fluid accumulation in uterus at diestrus and to a reduced implantation rate (43).…”