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Related Concept Videos

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The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
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Related Experiment Video

Updated: May 22, 2025

Fetal Echocardiography and Pulsed-wave Doppler Ultrasound in a Rabbit Model of Intrauterine Growth Restriction
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Assessing Placental Dysfunction Subtypes in Pregnancies With a Low PlGF Centile.

Kirsty M M Vincent1, Terence Garner1, Adam Stevens1

  • 1Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, United Kingdom (K.M.M.V., T.G., A.S., E.C.C., J.E.M., L.E.H.).

Hypertension (Dallas, Tex. : 1979)
|May 21, 2025
PubMed
Summary

Low placental growth factor (PlGF) may indicate placental dysfunction subtypes. Multiomic analysis identified two potential subtypes, one severe, aiding personalized treatment for pregnancy complications.

Keywords:
cluster analysishypertensionplacentapreeclampsia

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Area of Science:

  • Reproductive Biology
  • Genomics and Proteomics
  • Maternal-Fetal Medicine

Background:

  • Low circulating placental growth factor (PlGF) is a marker for placental dysfunction, a primary cause of preeclampsia and fetal growth restriction.
  • Current treatments are limited, and placental dysfunction's heterogeneity may hinder therapeutic development.
  • This study hypothesizes the existence of multiple subtypes of placental dysfunction in pregnancies with low PlGF.

Purpose of the Study:

  • To investigate the potential existence of distinct subtypes of placental dysfunction using multiomic analysis.
  • To correlate molecular subtypes with clinical outcomes in pregnancies with low PlGF.
  • To explore etiological differences between identified subtypes for personalized treatment strategies.

Main Methods:

  • Collected matched placental villous and maternal plasma samples from uncomplicated and complicated pregnancies (preeclampsia, fetal growth restriction, chronic hypertension).
  • Categorized samples based on circulating PlGF levels (low <5th centile vs. normal ≥5th centile).
  • Performed multiomic (transcriptomic and metabolomic) cluster-of-cluster analysis and compared clinical outcomes and pathway analysis between molecular clusters.

Main Results:

  • Multiomic analysis identified three molecular clusters.
  • Cluster 1 was predominantly associated with low PlGF and showed significantly lower birthweight and increased early-onset preeclampsia.
  • Pathway analysis revealed dysfunction-associated pathways primarily in cluster 2, not the clinically severe cluster 1, suggesting distinct etiological mechanisms.

Conclusions:

  • Multiomic analysis suggests at least two potential subtypes of placental dysfunction associated with low circulating PlGF.
  • Clinical outcomes suggest cluster 1 represents a severe subtype, but pathway analysis indicates different underlying mechanisms.
  • Understanding subtype-specific etiology is crucial for developing personalized therapeutic approaches for placental dysfunction.