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Updated: Nov 12, 2025

Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
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Modeling preeclampsia using human induced pluripotent stem cells.

Mariko Horii1,2, Robert Morey2,3, Tony Bui1,2

  • 1Department of Pathology, University of California San Diego, La Jolla, CA, 92093, USA.

Scientific Reports
|March 16, 2021
PubMed
Summary

Preeclampsia (PE) is a pregnancy disorder. PE-induced pluripotent stem cells show defective trophoblast syncytialization and hypoxia response, indicating placental dysfunction.

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Area of Science:

  • Reproductive biology
  • Stem cell biology
  • Maternal-fetal medicine

Background:

  • Preeclampsia (PE) affects up to 10% of pregnancies globally.
  • Abnormal trophoblast development is a key factor in PE etiology.
  • Human pluripotent stem cell differentiation protocols can model trophoblast development.

Purpose of the Study:

  • To investigate trophoblast differentiation using induced pluripotent stem cells (iPSCs) from PE pregnancies.
  • To model placental dysfunction in vitro.
  • To identify potential therapeutic targets for PE.

Main Methods:

  • Developed a two-step protocol for differentiating human pluripotent stem cells into trophoblast subtypes.
  • Applied this protocol to iPSCs derived from PE and control placentas.
  • Utilized RNA sequencing to analyze gene expression and DNA methylation.

Main Results:

  • PE-iPSC-derived trophoblasts exhibited impaired syncytialization and blunted hypoxia response.
  • RNAseq revealed defects in syncytiotrophoblast (STB) formation and hypoxia response.
  • DNA methylation changes were minimal, primarily related to hypoxia response.

Conclusions:

  • PE-iPSCs recapitulate key aspects of placental dysfunction observed in preeclampsia.
  • The maternal microenvironment significantly influences normal placentation.
  • Defects in trophoblast differentiation and response to hypoxia highlight potential diagnostic and therapeutic targets.