Modeling the Progression of Placental Transport From Early- to Late-Stage Pregnancy by Tuning Trophoblast Differentiation and Vascularization.

The early-stage placental barrier is characterized by a lack of fetal circulation and by a thick trophoblastic barrier, whereas the later-stage placenta consists of vascularized chorionic villi encased in a thin, differentiated trophoblast layer, ideal for nutrient transport. In this work, we created predictive models of early- and late-stage placental transport using blastocyst-derived placental stem cells (PSCs) by modulating PSC differentiation and model vascularization. PSC differentiation resulted in a thinner, fused trophoblast layer, as well as an increase in hCG secretion, barrier permeability and secretion of certain inflammatory cytokines, which are consistent with in vivo findings. Further, gene expression confirmed this shift towards a differentiated trophoblast subtype. Vascularization resulted in a molecule type- and size-dependent change in dextran and insulin permeability. These results demonstrate that trophoblast differentiation and vascularization have critical effects of placental barrier permeability and that our model could be used as a predictive measure to assess fetal toxicity of xenobiotic substances at different stages of pregnancy. This article is protected by copyright. All rights reserved.