Regulation of placental vascular endothelial growth/permeability factor expression and angiogenesis by estrogen during early baboon pregnancy

J Clin Endocrinol Metab. 2004 Nov;89(11):5803-9. doi: 10.1210/jc.2004-0479.


We have recently shown that there was a developmental increase in placental trophoblast vascular endothelial growth/permeability factor (VEG/PF) expression and vascularization that closely paralleled maternal serum estrogen levels during advancing baboon gestation. The present study determined whether estrogen regulates these important aspects of primate development. VEG/PF mRNA levels were determined by competitive RT-PCR in isolated villous placental cells, and placental vascularization was assessed by image analysis. Placentas were obtained on d 60 of gestation (length of gestation is 184 d) from baboons in which estrogen levels on d 25-59 were increased by daily administration of aromatizable androstenedione or decreased by aromatase inhibitor CGS 20267. Androstenedione treatment increased maternal serum estradiol levels 3-fold (P < 0.01) and placental villous cytotrophoblast VEG/PF mRNA level to a value (mean +/- se, 26,836 +/- 5,625 attomoles/microg total RNA) 2.5-fold greater (P < 0.05) than that in untreated animals (11,645 +/- 1,746 attomoles/microg RNA). In contrast, administration of CGS 20267 decreased serum estradiol (P < 0.01) and placental cytotrophoblast mRNA (2,912 +/- 693 attomoles/microg RNA; P < 0.05) levels by 75%, effects prevented by concomitant administration of CGS 20267 and estradiol. VEG/PF mRNA levels in inner villous cells were unaltered. Coinciding with the increase in placental VEG/PF expression, the percent vascularized area (3.46 +/- 0.23) and vessel density (493 +/- 34 vessels/mm(2)) of the villous placenta in untreated baboons on d 60 were increased (P < 0.01) in baboons in which estrogen levels were elevated by androstenedione treatment (6.54 +/- 0.56 and 743 +/- 27 vessels/mm(2), respectively). It is concluded that estrogen has an important role in stimulating trophoblast VEG/PF expression and consequently villous placental angiogenesis to promote fetal growth and development in early primate pregnancy.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Estradiol / blood
  • Estradiol / physiology*
  • Female
  • Fetal Weight
  • Gene Expression Regulation, Developmental*
  • Letrozole
  • Neovascularization, Physiologic*
  • Nitriles / pharmacology
  • Papio
  • Placenta / blood supply*
  • Pregnancy
  • Pregnancy, Animal / physiology*
  • RNA, Messenger / analysis
  • Triazoles / pharmacology
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor A / genetics*


  • Nitriles
  • RNA, Messenger
  • Triazoles
  • Vascular Endothelial Growth Factor A
  • Estradiol
  • Letrozole