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(American Journal of Pathology. 2005;166:1585-1592.)
© 2005 American Society for Investigative Pathology

Mechanism of Acute Fetal Cardiovascular Depression after Maternal Inflammatory Challenge in Mouse

Samuli Rounioja*, Juha Räsänen{dagger}, Marja Ojaniemi*, Virpi Glumoff*, Helena Autio-Harmainen{ddagger} and Mikko Hallman*

From the Department of Pediatrics and Biocenter Oulu,* and the Departments of Obstetrics and Gynecology{dagger} and Pathology,{ddagger} University of Oulu, Oulu, Finland

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-1{alpha}, 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.





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Review Article: Expression and Function of Toll-Like Receptors at the Maternal--Fetal Interface
Reproductive Sciences, March 1, 2008; 15(3): 231 - 242.
[Abstract] [PDF]




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Copyright © 2005 by the American Society for Investigative Pathology.