Regulation of placental villous angiopoietin-1 and -2 expression by estrogen during baboon pregnancy

Mol Reprod Dev. 2008 Mar;75(3):504-11. doi: 10.1002/mrd.20721.


We recently showed an increase in vascular endothelial growth factor (VEGF), decrease in angiopoietin-1 (Ang-1) and unaltered Ang-2 expression by the villous placenta with advancing baboon pregnancy. Moreover, placental VEGF expression was increased by estrogen in early pregnancy. In the present study, we determined whether placental Ang-1 and Ang-2 are regulated by estrogen. Ang-1 and Ang-2 mRNA and protein were determined by RT-PCR and immunocytochemistry in the placenta of baboons on Day 60 of gestation (term is 184 days) after administration of estrogen precursor androstenedione on Days 25-59 or on Day 54 after acute estradiol administration. Chronic androstenedione treatment increased serum estradiol levels three-fold (P < 0.001) and decreased (P < 0.05) villous cytotrophoblast Ang-1 mRNA to a level (0.36 +/- 0.08 relative to 18S rRNA) that was one-third of that in untreated animals (0.98 +/- 0.26). Within 2 hr of estradiol administration, cytotrophoblast Ang-1 mRNA was decreased to a level (0.24 +/- 0.05) one-fifth (P < 0.05) of that in untreated animals (1.14 +/- 0.23). However, Ang-2 mRNA levels were unaltered. Ang-1, Ang-2 and estrogen receptors alpha and beta protein were localized within villous cytotrophoblasts providing a mechanism for estrogen action at this site. In summary, estrogen increased VEGF, decreased Ang-1, and had no effect on Ang-2 expression within placental cytotrophoblasts during early baboon pregnancy. We propose that the estrogen-dependent differential regulation of these angioregulatory factors underpins the unique pattern of neovascularization established within the villous placenta during primate pregnancy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiopoietin-1 / genetics*
  • Angiopoietin-1 / metabolism
  • Angiopoietin-2 / genetics*
  • Angiopoietin-2 / metabolism
  • Animals
  • Chorionic Villi / metabolism*
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / metabolism
  • Estrogens / blood
  • Estrogens / pharmacology*
  • Female
  • Gene Expression Regulation / drug effects*
  • Male
  • Models, Biological
  • Papio / genetics*
  • Papio / physiology
  • Pregnancy
  • Pregnancy, Animal*
  • Progesterone / blood
  • RNA, Messenger / metabolism
  • Time Factors


  • Angiopoietin-1
  • Angiopoietin-2
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • RNA, Messenger
  • Progesterone