The trophectoderm layer of the mouse blastocyst differentiates at the late blastocyst stage to form the invasive trophoblast that mediates implantation of the embryo into the uterine wall. The first sign that trophoblast cells have developed an invasion-specific cell behavior appears about 10-15 hours after the embryo hatches from the zona pellucida, when the quiescent, nonadherent trophectoderm cells initiate protrusive activity and become adhesive to extracellular matrix. Our previous findings that trophoblast outgrowth on extracellular-matrix-coated substrata involves the integrin family of adhesion receptors (Sutherland, A. E., Calarco, P. G. and Damsky, C. H., 1988, J. Cell Biol. 106, 13311348), suggested that the onset of trophoblast adhesive and migratory behavior at the time of implantation may be due to changes in expression or distribution of integrin receptors. We have thus examined the mRNA and protein expression of individual integrin subunits during preand periimplantation development (E0E7.5). A basic repertoire of integrins, including receptors for fibronectin ( _{5 1}), laminin ( ₆B ₁) and vitronectin ( _{v 3}), was expressed continuously throughout this period, whereas the expression of five other integrin subunits was developmentally regulated. The mRNA for three of these ( _{2, 6}A and ₇) was first detected in the late blastocyst, coincident with endoderm differentiation and development of attachment competence. The mRNA for another ( ₁) was not detected until after trophoblast outgrowth had begun, suggesting that its expression may be induced by contact with matrix. At E7.5, three of the temporally regulated integrins (α₁, α₆A, α₇), all of which can form receptors for laminin, were detected only in the ectoplacental cone (differentiating trophoblast), and may thus play specific roles in trophoblast adhesion and/or differentiation.

Because laminin expression is upregulated in decidualized uterine stroma in response to the implanting embryo, we examined trophoblast-laminin interactions, using laminin fragments and integrin antibodies to determine which integrin receptors were involved. Trophoblast cells attached and spread on both the E8 and P1 fragments of laminin; however, the P1 binding site was cryptic in intact laminin. Interaction with P1 was RGDand α_vβ₃-dependent, whereas outgrowth on E8 was RGD-independent and not inhibited by antibodies to the laminin receptor α₆β₁, suggesting that α₇β₁ is the major trophoblast integrin E8 receptor. In contrast, migration of parietal endoderm cells on laminin was blocked by antibodies to α₆, demonstrating that these two contemporaneous migratory cell populations have different modes of interaction with laminin. We conclude that developmental regulation of integrin expression appears to have functional significance for trophoblast invasion of the laminin-rich uterine stroma.