Distribution patterns of extracellular matrix components and adhesion receptors are intricately modulated during first trimester cytotrophoblast differentiation along the invasive pathway in vivo

Abstract

Development of the human embryo depends on the ability of first trimester cytotrophoblastic stem cells to differentiate and invade the uterus. In this process transient expression of an invasive phenotype is part of normal cytotrophoblast differentiation. Morphologically this process begins when polarized chorionic villus cytotrophoblasts form multilayered columns of nonpolarized cells and invade the uterus. Using immunocytochemistry we compared the presence of adhesion receptors and extracellular matrix ligands on cytotrophoblasts in villi cell columns and the uterine wall. Villus cytotrophoblasts anchored to basement membrane stained for α6 and β34 integrin subunits and both merosin and A-chain-containing laminin. Nonpolarized cytotrophoblasts in columns expressed primarily α5 and β1 integrin subunits and a flbronectin-rich matrix. Cytotrophoblast clusters in the uterine wall stained for α1 α5 and β1 integrins but not for most extracellular matrix antigens suggesting that they interact primarily with maternal cells and matrices. Tenascin staining was restricted to stroma at sites of transition in cytotrophoblast morphology suggesting that tenascin influences cytotrophoblast differentiation. Our results suggest that regulation of adhesion molecule expression contributes to acquisition of an invasive phenotype by cytotrophoblasts and provide a foundation for studying pathological conditions in which insufficient or excessive trophoblast invasion occurs such as preeclampsia or choriocarcinoma.