Heme oxygenase-1 modulates fetal growth in the rat

Doron Kreiser, Xuandai Nguyen, Ron Wong, Daniel Seidman, David Stevenson, Shou Quan, Nader Abraham, Phyllis A. Dennery

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)687-692
Number of pages6
JournalLaboratory Investigation
Volume82
Issue number6
DOIs
StatePublished - Jun 2002

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