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Reconciling the distinct roles of angiogenic/anti-angiogenic factors in the placenta and maternal circulation of normal and pathological pregnancies

  • Anandita UmapathyEmail author
  • Lawrence W. Chamley
  • Joanna L. James
Review Paper


A branched vascular network is crucial to placental development and is dependent on factors such as vascular endothelial growth factor (VEGF), placental growth factor (PlGF), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) to regulate blood vessel growth. Imbalances in these factors can lead to aberrant placental vascular development. Throughout pregnancy, these factors are also released into the maternal circulation to aid in adapting the maternal cardiovascular system to pregnancy. Increased secretion of anti-angiogenic factors can lead to the development of an anti-angiogenic state in the mother and contribute to the development of pregnancy pathologies such as pre-eclampsia and foetal growth restriction (FGR). Thus, what are commonly referred to as ‘angiogenic factors’ have distinct functions in the maternal and placental circulations making this a misnomer. Indeed, technical issues in this field such as assay methodology and lack of data considering different placental cell types mean that the physiological roles of these factors in the maternal and placental circulations are frequently muddled in the literature. This review aims to (1) unpick the distinct roles of factors that influence placental vascular development and separate these from the roles of the same factors within the maternal circulation in normal pregnancy and (2) critically assess how imbalances may contribute to the distinct pathophysiological mechanisms underlying pregnancy disorders. Together, this critical assessment of the field endeavours to improve our ability to accurately use these factors as predictive/diagnostic biomarkers in the future.


Pregnancy Placenta Angiogenic factors Circulation Pre-eclampsia Foetal growth restriction 



This study was funded by the University of Auckland Doctoral Scholarship to Anandita Umapathy and the Health Research Council Sir Charles Hercus Research Fellowship to Joanna L. James (Grant Number 16/043).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Obstetrics and Gynaecology, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand

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