Expression And Regulation Of Foxp3 In Mouse Uterus

Embryo implantation is a key process in normal pregnancy. It has been proved that some cytokines, adhesion molecules, transcription factors and immune cells play important roles in the process of embryo implantation. Fork head box is a general term for the vertebrate fork head like transcription factor, usually associated with the regulation of cell growth and development. Foxp3 is a member of the Fox family, mainly expressed in the lymphoid organs of CD4+CD25+regulatory T cells(Treg), which can control the development and function of Treg cells. Studies have found that expression of Foxp3 was not confined to Treg cells, breast, lung, prostate, and endometrial glandular epithelial cells and some cancer cells were also found the expression of Foxp3 m RNA and protein. This suggests that Foxp3 may play roles as a transcription factor. This study was to investigate the expression and regulation of Foxp3 in mouse uterus by in situ hybridization, fluorescence quantitative PCR, RNA interference, etc.The in situ hybridization results showed that Foxp3 m RNA expressed in mouse uterine epithelium and glandular epithelium in the day 2-4 of pregnancy.In the fifth day of pregnancy, Foxp3 m RNA is mainly expressed in stromal cells surround the embryo. In the day 6-8 of pregnancy, Foxp3 m RNA is highly expressed in the decidual zone.Real-Time PCR results showed that the expression of Prl8a2 and Prl3c1 which were two well-known differentiation markers for decidualization can be reduced by the interference of Foxp3 gene or the Foxp3 inhibitor P60.This suggested that Foxp3 may be necessary for the differentiation of uterine stromal cells. Further research found that Foxp3 could mediate the effects of Runx1 on the decidualization marker molecule Prl8a2 and Prl3c1.The expression of Foxp3 can be significantly increased with c AMP analogues 8-Br-c AMP in uterine stromal cells, whereas the PKA pathway inhibitor H89 can hinder the effect. The effects of c AMP on the decidualization marker molecule Prl8a2 and Prl3c1 can be impaired by the interference of Foxp3 gene or the Foxp3 inhibitor P60.In addition, Runx1 could mediate the regulation of c AMP on Foxp3 and Foxp3 might act downstream of Runx1 to regulate the expression of Mmp2 in uterine stromal cells.In summary, Foxp3 may play an important role during uterine decidualization in mice and closely related to the differentiation of stromal cells.