Heme Oxygenase Protects against Placental Vascular Inflammation and Abortion by the Alarmin Heme in Mice.

Suttorp, Christiaan M; van Rheden, René E M; van Dijk, Natasja W M; Helmich, Maria P A C; Kuijpers-Jagtman, Anne Marie; Wagener, Frank A D T G (2020). Heme Oxygenase Protects against Placental Vascular Inflammation and Abortion by the Alarmin Heme in Mice. International journal of molecular sciences, 21(15) MDPI 10.3390/ijms21155385

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Both infectious as non-infectious inflammation can cause placental dysfunction and pregnancy complications. During the first trimester of human gestation, when palatogenesis takes place, intrauterine hematoma and hemorrhage are common phenomena, causing the release of large amounts of heme, a well-known alarmin. We postulated that exposure of pregnant mice to heme during palatogenesis would initiate oxidative and inflammatory stress, leading to pathological pregnancy, increasing the incidence of palatal clefting and abortion. Both heme oxygenase isoforms (HO-1 and HO-2) break down heme, thereby generating anti-oxidative and -inflammatory products. HO may thus counteract these heme-induced injurious stresses. To test this hypothesis, we administered heme to pregnant CD1 outbred mice at Day E12 by intraperitoneal injection in increasing doses: 30, 75 or 150 μmol/kg body weight (30H, 75H or 150H) in the presence or absence of HO-activity inhibitor SnMP from Day E11. Exposure to heme resulted in a dose-dependent increase in abortion. At 75H half of the fetuses where resorbed, while at 150H all fetuses were aborted. HO-activity protected against heme-induced abortion since inhibition of HO-activity aggravated heme-induced detrimental effects. The fetuses surviving heme administration demonstrated normal palatal fusion. Immunostainings at Day E16 demonstrated higher numbers of ICAM-1 positive blood vessels, macrophages and HO-1 positive cells in placenta after administration of 75H or SnMP + 30H. Summarizing, heme acts as an endogenous "alarmin" during pregnancy in a dose-dependent fashion, while HO-activity protects against heme-induced placental vascular inflammation and abortion.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > School of Dental Medicine > Department of Orthodontics

UniBE Contributor:

Kuijpers-Jagtman, Anne-Marie

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1422-0067

Publisher:

MDPI

Language:

English

Submitter:

Renate Imhof-Etter

Date Deposited:

18 Aug 2020 11:10

Last Modified:

05 Dec 2022 15:40

Publisher DOI:

10.3390/ijms21155385

PubMed ID:

32751152

Uncontrolled Keywords:

ICAM-1 abortion cleft palate embryology heme heme oxygenase inflammatory stress macrophage oxidative stress placenta vascular inflammation

BORIS DOI:

10.7892/boris.145948

URI:

https://boris.unibe.ch/id/eprint/145948

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