Heme oxygenase-1 modulates fetal growth in the rat.
Intrauterine growth restriction is associated with increased perinatal morbidity and mortality as well as with lifelong cardiovascular and metabolic complications. Deficiency of heme oxygenase 1 (HO-1) is associated with growth restriction in mice and in humans, suggesting a role for HO-1 in fetal growth and maintenance of pregnancy. We hypothesized that modulation of HO-1 in the pregnant rat would alter fetal growth. In pregnant dams, placental HO activity was significantly inhibited with zinc deuteroporphyrin IX 2,4 bis glycol, and HO-1 protein was increased by transducing adenoviral human HO-1. Inhibition of HO-1 by zinc deuteroporphyrin IX 2,4 bis glycol resulted in a significant decrease in pup size, whereas transfection with hHO-1 resulted in increased pup size. Furthermore, the expression of IGF binding protein-1 and its receptor paralleled the expression of HO-1 in the placenta and were significantly modulated by modification of HO-1 along with the expression of vascular endothelial growth factor. These observations demonstrate that HO-1 modulates fetal growth by its effects on placental growth factors.
Kreiser
Doron
D
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94304, USA.
Nguyen
Xuandai
X
Wong
Ron
R
Seidman
Daniel
D
Stevenson
David
D
Quan
Shou
S
Abraham
Nader
N
Dennery
Phyllis A
PA
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D003905:Deuteroporphyrins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D005822:Genetic Vectors; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008565:Membrane Proteins; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D003905:Deuteroporphyrins; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D018970:Insulin-Like Growth Factor Binding Protein 1; D008222:Lymphokines; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C060750:zinc deuteroporphyrin IX 2,4-bis(glycol); C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D017526:Receptor, IGF Type 1