PreImplantation Factor (PIF) Promotes Human Trophoblast Invasion

ABSTRACT Preimplantation factor (PIF) is a peptide secreted by viable mammalian embryos. Moreover, it can be detected in the circulation of pregnant women. Recently, it was shown that PIF promotes invasion in trophoblast cell lines in vitro. Successful human embryo implantation depends on a deep and highly controlled invasion of extravillous trophoblast (EVT) in the maternal endometrium. Trophoblast invasion is regulated in part by matrix metalloproteinase (MMP) activity and integrin expression. The present study demonstrates the presence of PIF in early pregnancy and characterizes its effects on primary human trophoblast invasion. At the fetomaternal interface, intense PIF labeling by immunohistochemistry was present during early gestation in villous trophoblasts and EVTs. A decrease of labeling was observed at term. Furthermore, PIF significantly promoted invasion of human EVT isolated from first-trimester placenta. The proinvasive regulatory effect of PIF in EVT was associated with 1) increased MMP9 ac...