The relationship between transplacental O2 diffusion and placental expression of PlGF, VEGF and their receptors in a placental insufficiency model of fetal growth restriction.
Placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) are involved in placental angiogenesis through interactions with the VEGFR-1 and VEGFR-2 receptors. The placenta of pregnancies whose outcome is fetal growth restriction (FGR) are characterized by abnormal angiogenic development, classically associated with hypoxia. The present study evaluated the near-term expression of this growth factor family in an ovine model of placental insufficiency-FGR, in relationship to uteroplacental oxygenation. Compared to controls, FGR pregnancies demonstrated a 37% increase in uterine blood flow (FGR vs. control, 610.86+/-48.48 vs. 443.17+/-37.39 ml min(-1) (kg fetus)(-1); P<0.04), which was associated with an increased maternal uterine venous PO2 (58.13+/-1.00 vs. 52.89+/-1.26 mmHg; P<0.02), increased umbilical artery systolic/diastolic ratio (3.90+/-0.33 vs. 2.12+/-0.26, P<0.05), and fetal hypoxia (arterial PO2; 12.79+/-0.97 vs. 18.65+/-1.6 mmHg, P<0.005). Maternal caruncle PlGF mRNA was increased in FGR (P<0.02), while fetal cotyledon VEGF mRNA was reduced (P<0.02). VEGFR-1 mRNA was also reduced in FGR fetal cotyledon (P<0.001) but was not altered in caruncle tissue. Immunoblot analysis of PlGF and VEGF demonstrated single bands at 19,000 and 18,600 Mr, respectively. Caruncle PlGF concentration was increased (P<0.04), while cotyledon VEGF was decreased (P<0.05) in FGR placentae. The data establish that uterine blood flow is not reduced in relationship to metabolic demands in this FGR model and that the transplacental PO2 gradient is increased, maintaining umbilical oxygen uptake per unit of tissue. Furthermore, these data suggest that an increased transplacental gradient of oxygen generates changes in angiogenic growth factors, which may underline the pathophysiology of the post-placental hypoxic FGR.
Regnault
Timothy R H
TR
Department of Pediatrics, Division of Perinatal Medicine, University of Colorado Health Sciences Center, Aurora, CO 80010, USA. tim.regnault@uchsc.edu
de Vrijer
Barbra
B
Galan
Henry L
HL
Davidsen
Meredith L
ML
Trembler
Karen A
KA
Battaglia
Frederick C
FC
Wilkening
Randall B
RB
Anthony
Russell V
RV
D000136:Acid-Base Equilibrium / Q000502:physiology; D000818:Animals; D015152:Blotting, Northern; D004326:Drinking / Q000502:physiology; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005333:Fetus / Q000098:blood supply; D005334:Fever / Q000503:physiopathology; D023282:Nuclease Protection Assays; D009929:Organ Size / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology*; D010920:Placenta / Q000098:blood supply / Q000378:metabolism*; D011247:Pregnancy; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis*; D012039:Regional Blood Flow; D015656:Respiratory Mechanics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2