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

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).

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 2018 Apr 20;8(1):6342. doi: 10.1038/s41598-018-24652-0.

Author information

1
Department of Obstetrics and Gynaecology, Reproductive Biology Unit, Medical University of Vienna, Vienna, Austria.
2
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
3
Department of Obstetrics and Gynaecology, Division of General Gynaecology and Gynaecologic Oncology, Medical University of Vienna, Vienna, Austria.
4
Forensic Toxicology, Clinical Institute of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
5
Children’s Cancer Research Institute, Vienna, Austria.
6
Section for Medical Statistics (IMS), Center of Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
7
Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
8
Gynmed Clinic, Vienna, Austria.
9
Division of Maternal and Fetal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States.
10
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. thomas.boehm@meduniwien.ac.at.
11
Department of Obstetrics and Gynaecology, Reproductive Biology Unit, Medical University of Vienna, Vienna, Austria. juergen.pollheimer@meduniwien.ac.at.

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.

PMID: 29679053
PMCID: PMC5910386
DOI: 10.1038/s41598-018-24652-0

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