title: Maternal endotoxin-induced preterm birth in mice: fetal responses in toll-like receptors, collectins, and cytokines.
abstract: Major cause of prematurity is spontaneous preterm birth (PTB) associated with intrauterine inflammation. Our aim was to establish a model of endotoxin Lipopolysaccharide-induced PTB of live-born pups and to study early immune activation in fetal and maternal compartments. Expression of several proteins that bind microbes (Toll-like receptors TLR4, TLR2; surfactant proteins SP-A, SP-D) was analyzed. At 16 or 17 d of gestation, C57BL/6 dams received a single dose of intraperitoneal LPS, leading to PTB within 17 h. Cytokine levels increased in maternal serum, followed by a modest increase in fetal serum and in amniotic fluid. In uterus, placenta, and fetal membranes, LPS mostly increased the expressions of TLR, SPs, and cytokines. The number of TLR2-positive macrophages increased in labyrinthine placenta. In fetal lung, intestine, liver, and brain there were modest changes in cytokine expressions. In fetal lung, SP and TLR mRNAs decreased and TLR2-positive macrophages redistributed around vessels. LPS-induced fetal deaths associated with early age (16 d gestation) rather than with proinflammatory activation. Here we propose that maternal LPS response leads to PTB and acute decrease of immune proteins in epithelial lining of fetal lung. Instead, acceleration of lung maturity has been previously observed in intraamniotic inflammation.
authors.affiliation: Department of Pediatrics, University of Oulu, Oulu, FIN-90014, Finland. annamari.salminen@oulu.fi
authors.forename: Annamari
authors.initials: A
authors.lastname: Salminen
authors.forename: Reija
authors.initials: R
authors.lastname: Paananen
authors.forename: Reetta
authors.initials: R
authors.lastname: Vuolteenaho
authors.forename: Juhani
authors.initials: J
authors.lastname: Metsola
authors.forename: Marja
authors.initials: M
authors.lastname: Ojaniemi
authors.forename: Helena
authors.initials: H
authors.lastname: Autio-Harmainen
authors.forename: Mikko
authors.initials: M
authors.lastname: Hallman
mesh_terms: D000653:Amniotic Fluid / Q000276:immunology; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D037222:Collectins / Q000097:blood / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005321:Extraembryonic Membranes / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D005313:Fetal Death; D005333:Fetus / Q000276:immunology*; D005865:Gestational Age; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000196:embryology / Q000276:immunology; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000276:immunology; D011247:Pregnancy; D047928:Premature Birth / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000097:blood / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014591:Uterine Diseases / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D014599:Uterus / Q000276:immunology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D037222:Collectins; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; D016753:Interleukin-10