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Reproductive Sciences, Vol. 14, No. 4, 315-320 (2007)
DOI: 10.1177/1933719107302959

Activation of Toll-like Receptors 2 or 3 and Preterm Delivery in the Mouse

Vladimir Ilievski, MD

Department of Obstetrics and Gynecology, Evanston Northwestern Healthcare, Evanston, Illinois

Shi-Jiang Lu, PhD

Advanced Cell Technology,Worchester, Massachusetts

Emmet Hirsch, MD

Department of Obstetrics and Gynecology, Evanston Northwestern Healthcare, Evanston, Illinois, e-hirsch{at}northwestern.edu

The objective of this study is to test whether the activation of toll-like receptors (TLRs) 2 and 3 (innate immune receptors for gram-positive and viral pathogens, respectively) can induce preterm delivery. One uterine horn of preterm pregnant CD-1 mice at approximately 75% of gestation was injected with TLR-2 ligands (lipoteichoic acid [LTA] or peptidoglycan [PGN]) or the TLR-3 ligand polyinosinic:cytidylic acid (poly[I:C]). Preterm delivery was recorded. In a separate group of mice, tissue mRNAs were quantified by reverse transcriptase polymerase chain reaction 5 hours after treatment with PGN or poly(I:C). Intrauterine PGN and LTA induced preterm delivery, reaching 100% at maximal doses. Intraperitoneal PGN also induced preterm delivery but at lower rates (maximum = 55%). Intrauterine poly(I:C) induced preterm birth in up to 31% of mice. Poly(I:C) induced uterine interferon ß and chemokine (C-C motif) ligand 5 (CCL5, also known as RANTES) but not interleukin 1ß, tumor necrosis factor, or lipopolysaccharide-induced CXC chemokine. PGN did not alter these mRNAs when compared with saline. Neither treatment induced gene expression in fetal membranes. Activation of either TLR-2 or -3 can induce preterm delivery in the mouse. Activation of TLR-3 with poly(I:C) induces interferon ß and the chemokine CCL5 in uterine tissues but not in fetal membranes.

Key Words: Toll-like receptors • preterm birth • animal model • chemokines.


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