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Heme oxygenase-1 modulates fetal growth in the rat
Doron Kreiser1, Xuandai Nguyen, Ron Wong
1Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94304, USA.
Insights
Heme oxygenase 1 (HO-1) plays a crucial role in fetal growth. Modulating HO-1 levels in pregnant rats directly impacts fetal size, highlighting its importance in pregnancy.
Area of Science:
- Reproductive biology
- Developmental biology
- Biochemistry
Background:
- Intrauterine growth restriction (IUGR) is linked to adverse perinatal outcomes and long-term health issues.
- Heme oxygenase 1 (HO-1) deficiency is associated with growth restriction in animal models and humans, suggesting its involvement in fetal development.
- The precise role of HO-1 in regulating fetal growth and pregnancy maintenance requires further elucidation.
Purpose of the Study:
- To investigate the hypothesis that modulating heme oxygenase 1 (HO-1) activity in pregnant rats affects fetal growth.
- To determine the impact of HO-1 inhibition and overexpression on placental function and fetal development.
Main Methods:
- Pregnant rats were treated to inhibit placental HO-1 activity using zinc deuteroporphyrin IX 2,4 bis glycol.
- HO-1 protein levels were increased via adenoviral transduction of human HO-1 (hHO-1).
- Fetal size, placental HO-1 expression, and the expression of insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were assessed.
Main Results:
- Inhibition of HO-1 led to a significant reduction in fetal pup size.
- Overexpression of HO-1 through hHO-1 transfection resulted in increased pup size.
- Placental expression of IGFBP-1 and its receptor, as well as VEGF, were modulated in parallel with HO-1 levels.
Conclusions:
- Heme oxygenase 1 (HO-1) significantly modulates fetal growth in a rat model.
- HO-1 influences fetal development through its effects on placental growth factors like IGFBP-1 and VEGF.
- These findings underscore the critical role of HO-1 in ensuring adequate fetal growth and successful pregnancy.
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.