Role of heme oxygenase 1 and human chorionic gonadotropin in pregnancy associated diseases

Heme oxygenase (HO) is the enzyme that catalyses heme breakdown to biliverdin, carbon monoxide, and ferrous ion. Biliverdin is rapidly converted to bilirubin by biliverdin reductase. HO-1, the inducible HO isoenzyme, is involved in placental development. HO-1 decreases the oxidative stress and promotes an immune tolerant microenvironment at the foetomaternal interface. This isozyme also regulates angiogenesis and vasculogenesis, and trophoblasts proliferation, migration and invasion, thus contributing to the adaptive changes in the uterine circulation to pregnancy. HO-1 expression is induced by several stimuli, including physical, chemical and biological agents. The reduced HO-1 expression and activity associated with adverse pregnancy outcomes in both humans and animal models. The human chorionic gonadotropin (hCG) is the first hormonal signal of pregnancy whose effects in pregnancy are mediated by HO-1. In this review, we summarise the current evidence showing the beneficial actions of HO-1 and hCG in early pregnancy. It is proposed that the biological effect of hCG in pregnancy is mediated by HO-1 upregulation. Noteworthy, humans quantitatively differ in their ability to up-regulate HO-1 due to the presence of an HMOX1 polymorphism in their proximal promoter region affecting its transcriptional activity. Consequently, a deficiency in HO-1 expression due to HMOX1 polymorphism may be considered as an underlying cause of human pregnancy disorders, particularly those related to placental dysfunction.