Physiological role of implantation-associated factor Mac25 and the molecular mechanisms of implantation

点击翻译按钮获取中文摘要

Mac25 (insulin-like growth factor binding protein-related protein 1) is highly expressed in the rat uterus around the time of implantation. We determined the peri-implantation localization of Mac25 mRNA and assessed the effects of recombinant Mac25 on the proliferative and prostacyclin (PGI_2)-producing abilities of cultured endometrial cells early in pregnancy. Mac25 mRNA was detected at high levels in endometrial stromal cells close to the smooth muscle of inter-implantation sites around the time of implantation but absent from decidual zones surrounding the embryo. Differential uterine Mac25 expression was also recognized in the delayed implanting pregnant model, but the level of mRNA decreased as decidual tissues formed in the decidualization model. Recombinant Mac25 inhibited the proliferation of endometrial stromal cells in vitro and arrested them in the G1 phase of the cell cycle. Furthermore, Mac25 significantly stimulated PGI_2 synthesis and cyclooxygenase-2 mRNA expression in myometrial cells, both of which are essential molecules for successful implantation. We constructed a recombinant adenovirus vector encoding Mac25 (Ad-mac) and transfected it to cultured uterine cells derived from early pregnant rats to know bioactivities of Mac25 in the uterus. Ad-mac infection caused increases in Mac25 protein detected in culture media within 72h. Overexpression of Mac25 enhanced expressions for cyclooxygenase-2 and prostaglandin E_2 syntheses mRNAs. These data suggest that Mac25 is an implantation-associated protein and that it modulates the proliferation of rat uterine cells and their production of PGI_2 during the peri-implantation period.