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Publication : 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.

First Author  Montalbano AP Year  2013
Journal  Endocrinology Volume  154
Issue  1 Pages  483-98
PubMed ID  23183169 Mgi Jnum  J:194208
Mgi Id  MGI:5471199 Doi  10.1210/en.2012-1797
Citation  Montalbano AP, et al. (2013) 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. Endocrinology 154(1):483-98
abstractText  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 (Mvarphi) 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 Mvarphi 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 ( approximately 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-1beta, IL-6, and CAP genes, connexin-43, and oxytocin receptor at 18.5 dpc compared with WT. F4/80(+) AF Mvarphis from TLR2(-/-) and SP-A/D(-/-) mice expressed significantly lower levels of both proinflammatory and antiinflammatory activation markers (e.g. IL-1beta, IL-6, ARG1, YM1) compared with gestation-matched WT AF Mvarphis. 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.
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