Trophoblast-specific expression and function of the integrin alpha 7 subunit in the peri-implantation mouse embryo

For implantation and placentation to occur, mouse embryo trophoblast cells must penetrate the uterine stroma to make contact with maternal blood vesse ls. A major component of the uterine epithelial basement membrane and under lying stromal matrix with which they interact is the extracellular matrix p rotein laminin. We have identified integrin alpha7 beta1 as a major recepto r for trophoblast-laminin interactions during implantation and yolk sac pla centa formation. It is first expressed by trophectoderm cells of the late b lastocyst and by all trophectoderm descendants in the early postimplantatio n embryo through E8.5, then disappears except in cells at the interface bet ween the allantois and the ectoplacental plate. Integrin alpha7 expression is a general characteristic of the early differentiation stages of rodent t rophoblast, given that two different cultured trophoblast cell lines also e xpress this integrin. Trophoblast cells interact with at least three differ ent laminin isoforms (laminins 1, 2/4, and 10/11) in the blastocyst and in the uterus at the time of implantation. Outgrowth assays using function-blo cking antibodies show that alpha7 beta1 is the major trophoblast receptor f or laminin I and a functional receptor for laminins 2/4 and 10/11. When tro phoblast cells are cultured on substrates of these three laminins, they att ach and spread on all three, but show decreased proliferation on laminin 1. These results show that the alpha7 beta1 integrin is expressed by trophobl ast cells and acts as receptor for several isoforms of laminin during impla ntation. These interactions are not only important for trophoblast adhesion and spreading but may also play a role in regulating trophectoderm prolife ration and differentiation. (C) 2001 Academic Press.