Homeostasis is maintained via regulation of osmotic gradients are largely established by epithelium

Various factors are involved in maintaining osmotic gradients; in particular, cystic fibrosis transmembrane conductance regulatorsfunction in cAMP-activated Cl2 secretion channelsand epithelial sodium channelsmediate the electrogenic influx of Na + across membranes. CFTRs and ENaCs are expressed in the murine female reproductive tract and human uterine epithelia. After mating in mice, decreased CFTR expression and increased ENaC expression are responsible for maximal fluid absorption, which ensures immobilization of the blastocyst and therefore successful implantation. So far, four subunits of ENaC have been cloned in mammals�C a, b, c and d�C and it is known that the a subunit is necessary for channel activity. A recent study showed that ENaC-a activation in the mouse endometrium is maximized at the time of implantation, and it regulates the production and release of prostaglandin E2, which is required for implantation. Moreover, Chen et al.found that CFTR-mediated oviductal HCO32 secretion may be vital for early embryo development. These studies suggest the key roles of CFTR and ENaC-a in embryo implantation and maintenance of pregnancy, but the exact mechanisms by which changes in ion channel expression can lead to pregnancy failure are unclear. Mating between female CBA and male DBA/2 mice is associated with an abortion rate of 20�C40%. As the repeatability of the high abortion rate in the peri-implantation stage is reliable in this mating, the CBA6DBA/2 model has been used to investigate the molecular mechanisms and signal pathways underlying early spontaneous abortion. However, there is no direct evidence of the role of ion channels in this model so far. Ion channels have been proved vital for reproduction, as previous research had studied ion channels in estrous cycle of miceor in human uteri during the pre-implantation period. However, ion channels expression in decidua after implantation, which potentially indicates what may go wrong at maternal-fetal interface, has not been investigated yet. After the uterine horns were sectioned longitudinally, the fetal-placental units were peeled from the underlying decidua and discarded, and the decidual tissue was scraped carefully from the uterine muscle. The decidual tissue for histology studies was left on the uterine wall. They had no history of vaginal bleeding and/or abdominal pain, and had not Cryptochlorogenic-acid undergone any hormonal treatment during pregnancy. Moreover, fetal development was normal according to the results of ultrasound examination. The maternal age and gestational age matched those in the abortion group. The decidual tissues of these pregnant women were obtained once the surgery was completed. The interaction between CFTR and ENaC has been proposed as the major mechanism regulating fluid Talatisamine absorption and secretion in the endometrial epithelia. It is considered that downregulated CFTR and upregulated ENaC in the endometrial epithelia of mice are required to achieve maximal fluid absorption necessary for successful implantation. The balance of these ion channels may be important in the cellular microenvironment during early pregnancy. In our study, the results demonstrate for the first time the differential expression of CFTR and ENaC-a between the decidual tissue of abortion-prone and normal pregnant mice. Overexpression of CFTR and inadequate expression of ENaC-a was observed in the decidua from abortion-prone mice and women who had a miscarriage.

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