Lefty promotes the proliferation and invasion of trophoblast cells by inhibiting nodal expression.

Trophoblast cells play a vital role in embryo implantation. Exploring cytokines secreted by trophoblast cells will be significant in revealing the molecular mechanism of embryo implantation. In vitro-cultured trophoblast cells treated with Lefty revealed that Lefty could downregulate the expression of Nodal while promoting the expression of MMP-2 and MMP-9. Thus, Lefty may promote the proliferation and invasion of trophoblast cells, thereby reducing the amount of apoptosis of these cells. Lefty siRNA knockdown or overexpression of Nodal showed opposite effects to treatment with Lefty. When trophoblast cells overexpressing Nodal were treated with Lefty, Nodal expression increased, and MMP-2 and MMP-9 expression was still promoted. Additionally, the proliferation and invasion of trophoblast cells were upregulated, and trophoblast apoptosis was reduced. Together, these data reveal that Lefty can promote the proliferation and invasion of trophoblast cells and inhibit their apoptosis by downregulating Nodal expression while promoting the expression of MMP-2 and MMP-9. This finding provides new proof for the mechanism of trophoblast cell invasion in decidua.