Models of the TSA-treated hESC and decidual hESCs.

<p><b>A,</b> In control endometrial stromal cells, trophoblast invasion is massive due to low levels of TIMPs and high levels of MMPs and uPA proteases. <b>B,</b> TSA-treated hESCs inhibits HDAC and promotes histone acetylation at the promoters of TIMP-1 and TIMP-3 by increasing the transcription of these genes. In contrast, the levels and activities of MMPs and uPA decrease. These ECM modulators changes reduced the motility of hESCs and the invasion of trophoblast cells. <b>C</b>, In <i>in vitro</i> decidualized hESCs, the intracellular cAMP levels increase and promote histone acetylation at the TIMP-1 and TIMP-3 gene promoters. Moreover, the activity and level of MMPs and uPA decreases and, together, precisely control the invasion of trophoblast cells.