A three-dimensional culture system recapitulates placental syncytiotrophoblast development and microbial resistance

Cameron A. McConkey, Elizabeth Delorme-Axford, Cheryl Nickerson, Kwang Sik Kim, Yoel Sadovsky, Jon P. Boyle, Carolyn B. Coyne

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

In eutherians, the placenta acts as a barrier and conduit at the maternal-fetal interface. Syncytiotrophoblasts, the multinucleated cells that cover the placental villous tree surfaces of the human placenta, are directly bathed in maternal blood and are formed by the fusion of progenitor cytotrophoblasts that underlie them. Despite their crucial role in fetal protection, many of the events that govern trophoblast fusion and protection from microbial infection are unknown. We describe a three-dimensional (3D)-based culture model using human JEG-3 trophoblast cells that develop syncytiotrophoblast phenotypes when cocultured with human microvascular endothelial cells. JEG-3 cells cultured in this system exhibit enhanced fusogenic activity and morphological and secretory activities strikingly similar to those of primary human syncytiotrophoblasts. RNASeq analyses extend the observed functional similarities to the transcriptome, where we observed significant overlap between syncytiotrophoblast-specific genes and 3D JEG-3 cultures. Furthermore, JEG-3 cells cultured in 3D are resistant to infection by viruses and Toxoplasma gondii, which mimics the high resistance of syncytiotrophoblasts to microbial infections in vivo. Given that this system is genetically manipulatable, it provides a new platform to dissect the mechanisms involved in syncytiotrophoblast development and microbial resistance.

Original languageEnglish (US)
Article numbere1501462
JournalScience Advances
Volume2
Issue number3
DOIs
StatePublished - Mar 2016

ASJC Scopus subject areas

  • General

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