Trophoblast differentiation during formation of anchoring villi in a model of the early human placenta in vitro

Abstract

In human implantation sites, formation of the cytotrophoblast shell and morphogenesis of anchoring villi occur during the 2nd and 3rd week of pregnancy. When placental villous tissue from 8-12 weeks was co-cultured with decidua parietalis, morphogenetic changes were observed specifically at sites of heterotypic contact, generating structures that closely resembled first trimester anchoring villi. Local breakdown of the syncytium and cytotrophoblast proliferation occurred, producing columns of cytotrophoblast. These columns showed complex changes of cell surface phenotype that replicate precisely the extravillous trophoblast differentiation pathway seen in vivo, including induction of integrin alpha 5 beta 1, loss of integrin alpha 6 beta 4 and expression of the HLA class I framework epitope recognized by monoclonal antibody W6/32. Extracellular matrix components including laminin, collagen type IV, fibrin and fibronectin were detected in intercytotrophoblastic spaces in the nascent columns. Spreading over the surface of the decidua and infiltration by cytotrophoblast were observed. We conclude that: (i) fist trimester floating villi retain the capacity to differentiate into anchoring villi; (ii) contact with decidua stimulates local breakthrough of the syncytium and cytotrophoblast proliferation; (iii) the resulting cytotrophoblast columns show phenotypic changes characteristic of these structures in vivo; and (iv) parietal decidua is capable of supporting implantation site-specific changes in a manner similar to the basal decidua.