New Insights into the Process of Placentation and the Role of Oxidative Uterine Microenvironment

Table 3

Soluble factors secretion and its effect on invasion.

	Soluble factor	Secreted by	Effects on trophoblast invasion	References
Proinvasive	CCL14	Decidua	Increase migration by promoting CAM expression alterations (α-catenin and integrin β5); increase invasion by increasing MMP-12 expression	[64, 78]
	CX3CL1			[78]
	EGF	Decidua and mesenchymal villi	Increase invasion by increasing MMP-9 and TIMP-1 expression	[65, 79–82]
	HGF	Decidua, placental stromal cells, and uNK	Increase invasion by upregulating of H2.0-like homeobox gene	[83, 84]
	IGFBP-1	Decidua	Increase invasion by increasing gelatinolytic activity	[31, 85–87]
	IL-1β	Cytotrophoblasts, decidua, macrophages, and uNK	Increase invasion by increasing MMP-2, MMP-9, and urokinase plasminogen activator expression	[78, 88–95]
	IL-6	Cytotrophoblasts and uNK	Increase invasion by increasing MMP-2 and MMP-9 expression	[91, 96–101]
	IL-8	Cytotrophoblasts, decidua, macrophages, and uNK	Increase invasion by increasing MMP-2, MMP-9, uPA, and plasminogen activator inhibitor (PAI) type 1 and 2 expression	[102, 103]
	IL-15	Decidual cells	Increase invasion by increasing MMP-1 expression	[76, 104, 105]
	IP-10	Endometrial stromal cells, uterine glandular cells, and uNK	Increase migration by increasing integrin expression (α5 and β3)	[106–108]
	LIF	Decidual stromal cells and uNK	Increase adhesion through changes in integrin expression; increase invasion by decreasing TIMP-1 expression	[109–115]
	RANTES	Uterine stromal cells	Increase adhesion and migration by increasing cytolytic activity and integrin expression (β1)	[116–118]
	IL-11	Cytotrophoblasts, uNK, and decidua	Involvement in EVT function less understood; inhibiting invasion in HTR-8/SVneo and increasing in JEG-3	[119–121]
Anti-invasive	CXCL14	Decidual stromal cells	Decrease invasion by gelatinase activity suppression	[64]
	IL-10	Macrophages and uNK	Decrease invasion by downregulating MMP-2 and MMP-9 expression	[122]
	INF-γ	Cytotrophoblasts, decidua, and uNK	Decrease invasion by decreasing insulin-like growth factor receptor-II	[123–127]
	Kisspeptin-10	Cytotrophoblasts and decidua	Decrease invasion by binding to g protein-coupled receptor kisspeptin-1 receptor increasing Ca^2+ intracellular levels	[123–127]
	TGF-β	Cytotrophoblasts, decidua, and uNK	Decrease invasion by increasing of TIMP-1 and TIMP-2 and plasminogen activator inhibitor type 1 and 2 expression; increases adhesion by upregulating the expression of CAM (ezrin and e-cadherin)	[62, 79, 85, 123–125, 128–130]
	TNF-α	Cytotrophoblasts, decidua, macrophages, and uNK	Decrease invasion by upregulation plasminogen activator inhibitor type 1 expression	[123, 125, 130–132]
	VEGF	Decidua, macrophages, and uNK	Decrease invasion by inhibiting urokinase plasminogen activator expression	[133]