title: Mechanism of acute fetal cardiovascular depression after maternal inflammatory challenge in mouse.
abstract: Intra-amniotic lipopolysaccharide (LPS) causes an acute inflammatory response and cardiac dysfunction in fetal mice. We hypothesized that the placenta protects the fetus against maternally administered bacterial toxins, delaying the onset of a fetal inflammatory response and vascular compromise. At 14 to 15 days of gestation, DBA mice were randomized to receive LPS (2.4 mg/kg) or vehicle intraperitoneally. Doppler ultrasonography of fetal cardiovascular hemodynamics was performed before and 6 hours after maternal LPS. Six hours after the LPS, maternal serum concentrations of tumor necrosis factor-alpha and interleukin (IL)-6 (P < 0.05) were increased. Placenta showed severe maternal vascular dilatation and congestion. The expressions of tumor necrosis factor-alpha, IL-1alpha, and IL-6 (P < 0.05) were increased, and the expression of Toll-like receptor 4 was constitutive in placenta. The expression of Toll-like receptor 2 increased (P < 0.05) and was detected in labyrinthine macrophages. No inflammatory activation was found in fetal tissues, and amniotic fluid revealed no significant increase in cytokines. The ultrasonographic examination demonstrated increased fetal cardiac afterload after LPS, with 65% of the fetuses exhibiting atrioventricular valve regurgitation. In conclusion, maternal inflammatory insult activates placental labyrinthine macrophages leading to an acute increase in placental vascular resistance and fetal cardiac dysfunction without an inflammatory response in fetus.
authors.affiliation: Department of Pediatrics and Biocenter Oulu, P.O. Box 5000, FIN-90014 University of Oulu, Finland. samuli.rounioja@oulu.fi
authors.forename: Samuli
authors.initials: S
authors.lastname: Rounioja
authors.forename: Juha
authors.initials: J
authors.lastname: Räsänen
authors.forename: Marja
authors.initials: M
authors.lastname: Ojaniemi
authors.forename: Virpi
authors.initials: V
authors.lastname: Glumoff
authors.forename: Helena
authors.initials: H
authors.lastname: Autio-Harmainen
authors.forename: Mikko
authors.initials: M
authors.lastname: Hallman
mesh_terms: D000653:Amniotic Fluid / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D015150:Echocardiography, Doppler; D005260:Female; D005315:Fetal Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D005333:Fetus; D015870:Gene Expression; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D010920:Placenta / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger