title: Mice deficient in surfactant protein A (SP-A) and SP-D or in TLR2 manifest delayed parturition and decreased expression of inflammatory and contractile genes.
abstract: Previously we obtained compelling evidence that the fetus provides a critical signal for the initiation of term labor through developmental induction of surfactant protein (SP)-A expression by the fetal lung and secretion into amniotic fluid (AF). We proposed that interactions of AF macrophage (Mϕ) Toll-like receptors (TLRs) with SP-A, at term, or bacterial components, at preterm, result in their activation and migration to the pregnant uterus. Herein the timing of labor in wild-type (WT) C57BL/6 mice was compared with mice homozygous null for TLR2, SP-A, SP-D, or doubly deficient in SP-A and SP-D. Interestingly, TLR2(-/-) females manifested a significant (P < 0.001) delay in timing of labor compared with WT as well as reduced expression of the myometrial contraction-associated protein (CAP) gene, connexin-43, and Mϕ marker, F4/80, at 18.5 d postcoitum (dpc). Whereas in first pregnancies, SP-A(-/-), SP-D(-/-), and SP-A/D(-/-) females delivered at term (∼19.5 dpc), in second pregnancies, parturition was delayed by approximately 12 h in SP-A(-/-) (P = 0.07) and in SP-A/D(-/-) (P <0.001) females. Myometrium of SP-A/D(-/-) females expressed significantly lower levels of IL-1β, IL-6, and CAP genes, connexin-43, and oxytocin receptor at 18.5 dpc compared with WT. F4/80(+) AF Mϕs from TLR2(-/-) and SP-A/D(-/-) mice expressed significantly lower levels of both proinflammatory and antiinflammatory activation markers (e.g. IL-1β, IL-6, ARG1, YM1) compared with gestation-matched WT AF Mϕs. These novel findings suggest that the pulmonary collectins acting via TLR2 serve a modulatory role in the timing of labor; their relative impact may be dependent on parity.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA.
authors.forename: Alina P
authors.initials: AP
authors.lastname: Montalbano
authors.forename: Samuel
authors.initials: S
authors.lastname: Hawgood
authors.forename: Carole R
authors.initials: CR
authors.lastname: Mendelson
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D008168:Lung / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009215:Myometrium / Q000166:cytology / Q000378:metabolism; D036801:Parturition / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2