Effects of histamine and diamine oxidase activities on pregnancy: a critical review

BACKGROUND: Histamine has been assumed to contribute to embryo–uterine interactions due to its vasoactive, differentiation and growth-promoting properties. However, its exact functions in pregnancy are unclear. The histamine-degrading enzyme diamine oxidase (DAO) is produced in high amounts by the placenta and has been supposed to act as a metabolic barrier to prevent excessive entry of bioactive histamine from the placenta into the maternal or fetal circulation. METHODS: The literature available on PubMed published in English between 1910 and 2008 has been searched using the isolated and combined key words histamine, diamine oxidase, pregnancy, placenta, endometrium, miscarriage, implantation, pre-eclampsia, intrauterine growth retardation, diabetes and embryonic histamine-releasing factor (EHRF). RESULTS: High expression of the histamine-producing enzyme histidine decarboxylase in the placenta, histamine receptors at the feto–maternal interface and the existence of an EHRF suggest a physiological role of histamine during gestation. The balance between histamine and DAO seems to be crucial for an uncomplicated course of pregnancy. Reduced DAO activities have been found in multiple heterogeneous complications of pregnancy such as diabetes, threatened and missed abortion and trophoblastic disorders. Whether women with histamine intolerance suffer from more complicated pregnancies and higher abortion rates due to impaired DAO activities and if low DAO levels or genetic modifications in the DAO gene might therefore represent a prognostic factor for a higher risk of abortion, has not been investigated yet. CONCLUSIONS: Low activities of the histamine-degrading enzyme DAO might indicate high-risk pregnancies, although high intraand interindividual variations limit its value as a screening tool.