Pregnancy-associated diamine oxidase originates from extravillous trophoblasts and is decreased in early-onset preeclampsia

Abstract

Human extravillous trophoblast (EVT) invasion of the pregnant uterus constitutes a pivotal event for the establishment of the maternal-fetal interface. Compromised EVT function manifesting in inadequate arterial remodeling is associated with the severe pregnancy disorder early-onset preeclampsia (eoPE). Recent studies suggest that EVTs invade the entire uterine vasculature including arteries, veins and lymphatics in the first trimester of pregnancy. We therefore hypothesized that EVT-derived factors accumulate in the circulation of pregnant women early in gestation and may serve to predict eoPE. In contrast to published literature, we demonstrate that placenta-associated diamine oxidase (DAO) is not expressed by maternal decidual cells but solely by EVTs, especially when in close proximity to decidual vessels. Cultures of primary EVTs express and secret large amounts of bioactive DAO. ELISA measurements indicate a pregnancy-specific rise in maternal DAO plasma levels around gestational week (GW) 7 coinciding with vascular invasion of EVTs. Strikingly, DAO levels from eoPE cases were significantly lower (40%) compared to controls in the first trimester of pregnancy but revealed no difference at mid gestation. Furthermore, DAO-containing pregnancy plasma rapidly inactivates pathophysiologically relevant histamine levels. This study represents the first proof of concept suggesting EVT-specific signatures as diagnostic targets for the prediction of eoPE.

Regulation of histamine and diamine oxidase in patients undergoing orthotopic liver transplantation

“…Thus, the increased baseline concentration of DAO might be explained by a decreased clearance of DAO in patients with ESLD. The most striking finding of this study was the manifold increase in DAO concentrations during OLT comparable in magnitude to early pregnancy 27 , and the likely resultant inverse correlation between DAO and histamine. The increase in systemic concentration of DAO during OLT can explain the degradation of histamine.…”

“…The increase in systemic concentration of DAO during OLT can explain the degradation of histamine. We have recently shown that plasma levels of DAO (29-52 ng/mL) comparable to those observed in the anhepatic phase can rapidly lower plasma histamine concentrations by ~50-85% within 10 minutes 27 . Thus, the increase in DAO is a mechanistic explanation for the observed decrease in histamine concentrations in patients undergoing OLT.…”

“…Norepinephrine is used to counteract hypotension which can result in or reflect intestinal hypoxemia, which may itself trigger DAO release. For example, hemorrhagic shock increased DAO levels 6-fold in rabbits 27 , and an hour of intestinal ischemia increased DAO concentrations 3.6-fold in rats 24 . Such an increase in DAO is conceivably accentuated in the presence of decreased clearance of DAO during the (2020) 10:822 | https://doi.org/10.1038/s41598-020-57728-x www.nature.com/scientificreports www.nature.com/scientificreports/ anhepatic phase.…”

Massive release of the histamine‐degrading enzyme diamine oxidase during severe anaphylaxis in mastocytosis patients

“…The development and characterization of the human DAO ELISA was recently published in detail . We tested two commercially available DAO ELISA kits but they were not reliable to measure human DAO …”

“…In humans, high DAO mRNA and activity are found in the gastrointestinal tract, kidney, and placenta . Expression in the placenta is restricted to extravillous trophoblast cells and therefore of fetal and not as assumed for decades of maternal origin . Plasma DAO concentrations increase at least 100‐fold during pregnancy, but the physiological function of this rise is not clear.…”