TY - JOUR
T1 - 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
AU - Montalbano, Alina P.
AU - Hawgood, Samuel
AU - Mendelson, Carole R.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
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U2 - 10.1210/en.2012-1797
DO - 10.1210/en.2012-1797
M3 - Article
C2 - 23183169
AN - SCOPUS:84871683969
SN - 0013-7227
VL - 154
SP - 483
EP - 498
JO - Endocrinology
JF - Endocrinology
IS - 1
ER -