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Human Placental Genomic Instability Predicts Adverse Pregnancy Outcomes.

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Genomic instability in the placenta is linked to preeclampsia, increasing the risk of early delivery and adverse outcomes. This placental instability may serve as a biomarker for early preeclampsia diagnosis.

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Area of Science:

  • Obstetrics and Gynecology
  • Genetics
  • Perinatal Medicine

Background:

  • Preeclampsia is a major global cause of maternal and fetal mortality.
  • Confined placental mosaicism suggests placental genomic instability may contribute to adverse pregnancy outcomes.
  • Understanding placental dysfunction is crucial for improving pregnancy outcomes.

Purpose of the Study:

  • To investigate the association between placental genomic instability, hypoxia, and adverse pregnancy outcomes in preeclampsia.
  • To explore the functional role of genomic instability in trophoblast cells.
  • To identify potential biomarkers for early clinical diagnosis of preeclampsia.

Main Methods:

  • Bulk RNA sequencing was performed on placentas from 59 preeclamptic and 53 normotensive pregnancies.
  • Somatic genomic instability and hypoxia were analyzed in relation to clinical outcomes.
  • An induced pluripotent stem cell-derived trophoblast stem cell model was used to assess genomic instability in trophoblasts.

Main Results:

  • Genomic instability was associated with earlier gestational age at delivery, preeclampsia diagnosis, maternal vascular malperfusion lesions, and small for gestational age neonates.
  • Genomic instability and hypoxia were identified as predictive biomarkers for these adverse outcomes.
  • Increased genomic instability in trophoblast stem cells correlated with reduced extravillous trophoblast invasion.

Conclusions:

  • Placental genomic instability is implicated in the pathophysiology of preeclampsia and adverse pregnancy outcomes.
  • Genomic instability and hypoxia show potential as predictive biomarkers for preeclampsia.
  • These findings offer insights into placental genomic instability mechanisms and potential diagnostic applications.