Regulation of placental vascular endothelial growth/permeability factor expression and angiogenesis by estrogen during early baboon pregnancy.
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.
Albrecht
Eugene D
ED
Department of Obstetrics, Gynecology, Center for Studies in Reproduction, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ealbrech@umaryland.edu.
Robb
Victoria A
VA
Pepe
Gerald J
GJ
D000818:Animals; D004958:Estradiol / Q000097:blood / Q000502:physiology*; D005260:Female; D020567:Fetal Weight; D018507:Gene Expression Regulation, Developmental; D000077289:Letrozole; D018919:Neovascularization, Physiologic; D009570:Nitriles / Q000494:pharmacology; D010215:Papio; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D014230:Triazoles / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics*
D009570:Nitriles; D012333:RNA, Messenger; D014230:Triazoles; D042461:Vascular Endothelial Growth Factor A; D004958:Estradiol; D000077289:Letrozole