Trophoblast cells exhibit differential responses to laminin isoforms

Abstract

Extracellular matrix (ECM) has specific effects on cell behavior that influence many aspects of early development. In the early postimplantation mouse embryo the ECM component laminin promotes polarization and survival of the embryonic ectoderm and formation of Reichert's membrane. In addition, dynamic patterns of laminins 1 and 10/11 expression in the embryo and the uterus correlate with the progression of implantation. In the implanting blastocyst, laminin 1 is strongly expressed in the trophectoderm basement membrane, whereas laminin 10/11 is expressed only in the inner cell mass and polar trophectoderm. In the uterus, laminin 10/11 is strongly expressed in the decidualizing matrix of the stroma. We show here that laminins 1 and 10/11 have distinct effects on trophoblast cell behavior that influence the process of implantation. Laminin 1 promotes random migration and decreases spreading, whereas laminin 10/11 promotes both spreading and persistent migration. When presented as adjacent substrates, cells stop at the boundary and do not enter the region containing laminin 1. Laminin 1 also affects cell–cell adhesion through changes in the localization of vascular endothelial (VE) cadherin. Cultured cells and primary trophoblast explants become single cells or very small groups on laminin 1 and VE-cadherin localization at regions of cell–cell contact decreases dramatically. In contrast, trophoblast cells maintain strong cell–cell contacts on substrates of laminins 10/11, and exhibit strong staining of VE-cadherin in all regions of cell–cell contact. These effects, and the localization of laminin 1 in Reichert's membrane and laminin 10/11 in the surrounding decidual matrix, suggest that these laminin isoforms influence the direction and quality of invasion of trophoblast cells during implantation, and provide epigenetic cues that drive the morphogenesis of the yolk sac placenta.