Heme Oxygenase Biology (During the Perinatal Period): Part 1: Prenatal Considerations

Abstract

Heme oxygenase (HO), the rate-limiting enzyme in heme degradation, and its byproducts have antioxidative, antiapoptotic, anti-inflammatory, and cytoprotective properties. The expression of the inducible isoform, HO-1, in various tissues is increased in newborns, decreases toward adulthood, and may be of pivotal importance during the perinatal period. During pregnancy, it may mediate the regulation of maternal blood pressure, placental development, and vascularization, and, therefore, the maintenance of a healthy pregnancy. Pregnancy disorders, such as intrauterine growth restriction and preeclampsia, contribute significantly to preterm births as well as to perinatal morbidity and mortality and manifest even into adulthood. They stem from placental defects mediated by fetal genetic defects, maternal factors, or both. HO-1 has been shown to play a role in the maintenance of maternal inflammatory homeostasis and normal placental vasculature development by regulating angiogenesis and matrix remodeling in early pregnancy. Therefore, a genetic deficiency in HO-1 gene expression may be an underlying cause of pregnancy disorders, in particular, those attributed to placental dysfunction.