Hypoxia pp 259-275 | Cite as

Oxygen and Placental Vascular Development

  • John C. P. Kingdom
  • Peter Kaufmann
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 474)


Human embryogenesis takes place in a hypoxic environment because the trophoblast shell excludes entry of maternal blood. The first fetal-placental villi develop as trophoblast sprouts. These are invaded by allantoic mesoderm to form secondary villi and are transformed, by vasculogenesis, into tertiary villi. The placental barrier to maternal blood is gradually breached between 8–12 weeks of gestation, due to invasion of placental-bed uteroplacental spiral arteries by the extravillous trophoblast (EVT). Placental oxygen tension thus rises and a phase of branching angiogenesis continues until 24 weeks. Thereafter a gradual shift takes place favoring non-branching angiogenesis. Gas-exchanging terminal villi thus form which are essential for rapid fetal growth and development of a high-flow, low-resistance fetal-placental circulation.

Inadequate invasion of the uteroplacental spiral arteries by EVT results in placental ischemia and the development of obstetrical complications - preeclampsia and/or intrauterine growth restriction (IUGR). Placental villi often show evidence of continued branching angiogenesis, as is the case with anemic pregnancy, and pregnancy at high altitude. These structural alterations may reflect continued hypoxia-driven activity of vascular endothelial growth factor (VEGF). By contrast, a minority of severe early-onset IUGR pregnancies exhibit reduced fetal-placental blood flow with elongated maldeveloped villous capillaries. Placenta-like growth factor (P1GF) expression is increased while trophoblast proliferation is reduced, suggesting “hyperoxia” in the placental villous tree. IUGR may thus have two phenotypes - a more common hypoxic and a rarer hyperoxic type. While this concept is gaining acceptance, we have no insight as to the initiating mechanism(s).

Key words

embryogenesis vasculogenesis fetal-placental circulation intrauterine growth restriction placenta-like growth factor placenta 


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Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • John C. P. Kingdom
    • 1
    • 2
  • Peter Kaufmann
    • 1
    • 2
  1. 1.Department of Obstetrics & GynecologyUniversity of Toronto and Maternal-Fetal Medicine DivisionTorontoCanada
  2. 2.Department of AnatomyUniversity of TechnologyAachenGermany

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