Hypoxic treatment of human dual placental perfusion induces a preeclampsia-like inflammatory response.

Jain, Arjun; Schneider, Henning; Aliyev, Eldar; Soydemir, Fatimah; Baumann, Marc Ulrich; Surbek, Daniel; Hediger, Matthias; Brownbill, Paul; Albrecht, Christiane (2014). Hypoxic treatment of human dual placental perfusion induces a preeclampsia-like inflammatory response. Laboratory investigation, 94(8), pp. 873-880. Nature Publishing Group 10.1038/labinvest.2014.76

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Preeclampsia is a human pregnancy-specific disorder characterized by a placental pro-inflammatory response in combination with an imbalance of angiogenic factors and clinical symptoms, including hypertension and proteinuria. Insufficient uteroplacental oxygenation in preeclampsia due to impaired trophoblast invasion during placentation is believed to be responsible for many of the molecular events leading to the clinical manifestations of this disease. We investigated the use of hypoxic treatment of the dual placental perfusion system as a model for preeclampsia. A modified perfusion technique allowed us to achieve a mean soluble oxygen tension within the intervillous space (IVS) of 5-7% for normoxia and <3% for hypoxia (as a model for preeclampsia). We assayed for the levels of different inflammatory cytokines, oxidative stress markers, as well as other factors, such as endothelin (ET)-1 that are known to be implicated as part of the inflammatory response in preeclampsia. Our results show a significant increase under hypoxia in the levels of different inflammatory cytokines, including IL-6 (P=0.002), IL-8 (P<0.0001), TNF-α (P=0.032) and IFN-γ (P=0.009) at 360 min in maternal venous samples (n=6). There was also a significant increase in ET-1 levels under hypoxia both on the maternal side at 30 min (P=0.003) and fetal side at 360 min (P=0.036) (n=6). Other markers of oxidative stress, including malondialdehyde and 8-iso-protaglandin F2α (P=0.009) also show increased levels. Overall, these findings indicate that exposure of ex vivo dually perfused placental tissue to hypoxia provides a useful model for mimicking the inflammatory response characteristic of preeclampsia. This would therefore provide a powerful tool for studying and further delineating the molecular mechanisms involved in the underlying pathophysiology of preeclampsia.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology

UniBE Contributor:

Jain, Arjun; Schneider, Henning; Aliyev, Eldar; Baumann, Marc Ulrich; Surbek, Daniel; Hediger, Matthias and Albrecht, Christiane

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0023-6837

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

10 Feb 2015 11:17

Last Modified:

02 Sep 2015 10:22

Publisher DOI:

10.1038/labinvest.2014.76

PubMed ID:

24933425

BORIS DOI:

10.7892/boris.62831

URI:

https://boris.unibe.ch/id/eprint/62831

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