Runx1 transcription factor is a key developmental regulator. However, little is known about the effects of Runx1 on embryo implantation and decidualization. The aim of this study is to examine the expression and regulation of Runx1 in mouse uterus during the peri-implantation period. There was no evident Runx1 mRNA signal on days 1-4 of pregnancy. On day 5 of pregnancy, Runx1 mRNA was mainly localized in the subluminal stroma surrounding the implanting blastocyst. A similar result was observed in the estrogen-activated implantation uterus. Simultaneously, a high level of Runx1 mRNA expression was detected on days 6-8 of pregnancy and under artificial decidualization. 8-Br-cAMP could induce the expression of Runx1 mRNA in the uterine stromal cells. Moreover, the induction was obviously blocked by PKA inhibitor H89. Inhibition of Runx1 with specific siRNA could decrease the proliferation of stromal cells and expression of decidual markers Prl8a2 and Prl3c1 in the uterine stromal cells. Further study found that inhibition of Runx1 could also suppress the expression of Cox-2, mPGES-1 and Mmp2 genes in uterine stromal cells. Estrogen and progesterone could induce the expression of Runx1 mRNA in ovariectomized mouse uterus and uterine stromal cells. Taken together, these data suggest that Runx1 may play an important role during mouse decidualization.
Although Runx2 is involved in the regulation of cellular differentiation, its physiological roles in the differentiation of uterine stromal cells during decidualization still remain unknown. The aim of this study was to examine the expression, regulation and function of Runx2 in mouse uterus during decidualization. The results showed that Runx2 was highly expressed in the decidua and oil-induced decidualized cells. In the uterine stromal cells, recombinant human Runx2 (rRunx2) could induce the expression of Prl8a2 and Prl3c1 which are two well-known differentiation markers for decidualization, while inhibition of Runx2 with specific siRNA reduced their expression. Further study found that rRunx2 could improve the expression of Prl8a2 and Prl3c1 in the C/EBPβ siRNA-transfected stromal cells. In the stromal cells, cAMP analogue 8-Br-cAMP could induce the expression of Runx2. Moreover, the induction was blocked by PKA inhibitor H89. Simultaneously, attenuation of C/EBPβ with siRNA could also reduce the cAMP-induced Runx2 expression. Furthermore, siRNA-mediated silencing of Runx2 expression alleviated the effects of cAMP on the differentiation of stromal cells. Runx2 might act downstream of C/EBPβ to regulate the expression of Cox-2, Vegf and Mmp9 in the uterine stromal cells. Collectively, Runx2 may play an important role during mouse decidualization.
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