Department of Pathophysiology, Faculty of Biological Sciences, Universidad de Concepción, Concepción 4089100, Chile.
Department of Obstetrics and Gynaecology; Faculty of Medicine, Universidad de Concepción, Concepción 4089100, Chile.
Biochim Biophys Acta Mol Basis Dis. 2020 Feb 1;1866(2):165522. doi: 10.1016/j.bbadis.2019.07.016. Epub 2019 Jul 31.
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.
血红素加氧酶（HO）是一种酶，可催化血红素分解为胆绿素、一氧化碳和亚铁离子。胆绿素被胆绿素还原酶迅速转化为胆红素。HO-1，即诱导型 HO 同工酶，参与胎盘发育。HO-1 可降低氧化应激，并在胎-母界面促进免疫耐受的微环境。该同工酶还调节血管生成和血管发生，以及滋养细胞的增殖、迁移和侵袭，从而有助于子宫循环适应妊娠的变化。HO-1 的表达受多种刺激物诱导，包括物理、化学和生物因子。HO-1 表达和活性的降低与人类和动物模型中的不良妊娠结局相关。人绒毛膜促性腺激素（hCG）是妊娠的第一个激素信号，其在妊娠中的作用是通过 HO-1 介导的。在这篇综述中，我们总结了目前的证据，表明 HO-1 和 hCG 在早孕中的有益作用。据推测，hCG 在妊娠中的生物学效应是通过 HO-1 的上调介导的。值得注意的是，由于其近端启动子区域存在 HMOX1 多态性，影响其转录活性，人类在 HO-1 的上调能力上存在定量差异。因此，由于 HMOX1 多态性导致的 HO-1 表达不足可能被认为是人类妊娠疾病的潜在原因，尤其是与胎盘功能障碍相关的疾病。
