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Membrane protected apoptotic trophoblast microparticles contain nucleic acids: relevance to preeclampsia

Aaron F Orozco1, Carolina J Jorgez, Cassandra Horne

  • 1Department of Immunology, Baylor College of Medicine, Houston, TX, USA.

The American Journal of Pathology
|November 1, 2008
PubMed

Insights

Circulating microparticles (MPs) from dying cells carry stable DNA, useful for prenatal genetic diagnosis. Apoptotic MPs in maternal plasma increase with preeclampsia, aiding pregnancy monitoring.

Area of Science:

  • Obstetrics and Gynecology
  • Molecular Biology
  • Biochemistry

Background:

  • Circulating microparticles (MPs) are potential sources of DNA for prenatal genetic testing.
  • Heterogeneity of MPs necessitates characterization before clinical application.
  • Key question: Is MP-associated DNA protein/lipid-bound or from dying cells?

Purpose of the Study:

  • To investigate if in vitro-derived MPs from dying cells resemble maternal plasma MPs.
  • To characterize DNA content and stability in MPs from apoptotic versus necrotic cells.
  • To assess the potential of apoptotic MPs as a source for prenatal genetic analysis.

Main Methods:

  • JEG-3 cells (extravillous trophoblast model) induced into apoptosis and necrosis.
  • Analysis of DNA fragmentation and DNase resistance in MPs.
  • Flow cytometry using membrane-specific dyes and DNA staining.
  • Comparison of in vitro MPs with those from maternal plasma.

Main Results:

  • Apoptotic MPs showed increased, more fragmented, and DNase-resistant DNA compared to necrotic MPs.
  • Apoptotic MPs exhibited greater membranous material, protecting nucleic acids.
  • Flow cytometry revealed MPs from dying cells share characteristics with maternal plasma MPs.
  • Significantly higher DNA(+) MPs observed in preeclampsia patients versus normal pregnancies.

Conclusions:

  • Apoptotic microparticles are a likely source of stable DNA for molecular analyses.
  • Characterized MPs can be used for early genetic diagnosis and monitoring of pathological pregnancies.
  • Findings support the clinical utility of apoptotic MPs in prenatal diagnostics.

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