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A Novel Three-Dimensional In Vitro System to Study Trophoblast–Endothelium Cell Interactions

Authors

  • Paulomi B. Aldo,

    1.  Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT, USA
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  • Graciela Krikun,

    1.  Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT, USA
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  • Irene Visintin,

    1.  Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT, USA
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  • Charles Lockwood,

    1.  Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT, USA
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  • Roberto Romero,

    1.  Perinatology Research Branch, National Institute of Child Health and Human Development, Detroit, MI, Bethesda, MD, USA
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  • Gil Mor

    1.  Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT, USA
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Gil Mor, Department of Obstetrics, Gynecology, and Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, 333 Cedar Street, FMB 301, New Haven, CT 06520, USA.
E-mail: gil.mor@yale.edu.

Abstract

Introduction

Pregnancy complications have been linked to improper trophoblast migration and failure of spiral artery transformation. Endothelial cells play an essential role in directing trophoblast migration and transformation, although by an unknown mechanism. We describe a novel in vitro model to evaluate endothelial–trophoblast interaction and signaling in a three-dimensional system.

Method of study

Immortalized human endometrial endothelial cell line and first trimester trophoblast cells were co-cultured. Endothelial transformation into vessel-like structures occurred in MatrigelTM OpenLab Image Analysis software was used to monitor labeled trophoblast migration and endothelium transformation. Cytokine/chemokine production was determined using Multiplex.

Results

Trophoblast migrates toward endothelial cells in Matrigel, aligns on top of the endothelium within 4–8 hr and achieves complete replacement of the endothelium by 72–96 hr. Lipopolysaccharide treatment damages the endothelium and disrupts endothelium–trophoblast interaction.

Conclusion

We report a novel three-dimensional in vitro and in vivo system of trophoblast–endothelium cell interaction. Significant changes in endothelial cells’ phenotype are observed upon differentiation in Matrigel. These changes may be necessary for endothelium to direct trophoblast migration and transformation.

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