Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenoviridae / genetics
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Animals
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Animals, Newborn
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Deuteroporphyrins / pharmacology
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Dose-Response Relationship, Drug
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Endothelial Growth Factors / metabolism
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Enzyme Inhibitors / pharmacology
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Female
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Fetal Weight / drug effects
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Genetic Vectors
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Heme Oxygenase (Decyclizing) / antagonists & inhibitors
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Heme Oxygenase (Decyclizing) / genetics
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Heme Oxygenase (Decyclizing) / metabolism*
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Heme Oxygenase-1
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Humans
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Insulin-Like Growth Factor Binding Protein 1 / metabolism
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Lymphokines / metabolism
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Membrane Proteins
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Placenta / drug effects
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Placenta / enzymology
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Pregnancy
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Rats
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Rats, Wistar
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Receptor, IGF Type 1 / metabolism
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Transduction, Genetic
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Deuteroporphyrins
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Endothelial Growth Factors
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Enzyme Inhibitors
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Insulin-Like Growth Factor Binding Protein 1
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Lymphokines
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Membrane Proteins
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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zinc deuteroporphyrin IX 2,4-bis(glycol)
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HMOX1 protein, human
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Heme Oxygenase (Decyclizing)
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Heme Oxygenase-1
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Receptor, IGF Type 1