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Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition
Jennifer C. Condon *,
Pancharatnam Jeyasuria,
Julie M. Faust *, and
Carole R. Mendelson *
Departments of *Biochemistry, Obstetrics and Gynecology, and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390
Communicated by Jean D. Wilson, University of Texas Southwestern Medical Center, Dallas, TX, February 18, 2004
Received for publication December 26, 2003.
Abstract:
Parturition is timed to begin only after the developing embryois sufficiently mature to survive outside the womb. It has beenpostulated that the signal for the initiation of parturitionarises from the fetus although the nature and source of thissignal remain obscure. Herein, we provide evidence that thissignal originates from the maturing fetal lung. In the mouse,secretion of the major lung surfactant protein, surfactant proteinA (SP-A), was first detected in amniotic fluid (AF) at 17 dayspostcoitum, rising progressively to term (19 days postcoitum).Expression of IL-1 in AF macrophages and activation of NF-Bin the maternal uterus increased with the gestational increasein SP-A. SP-A stimulated IL-1 and NF-B expression in culturedAF macrophages. Studies using Rosa 26 Lac-Z (B6;129S-Gt(rosa)26Sor)(Lac-Z) mice revealed that fetal AF macrophages migrate to theuterus with the gestational increase in AF SP-A. Intraamniotic(i.a.) injection of SP-A caused preterm delivery of fetuseswithin 6-24 h. By contrast, injection of an SP-A antibody orNF-B inhibitor into AF delayed labor by >24 h. We proposethat augmented production of SP-A by the fetal lung near termcauses activation and migration of fetal AF macrophages to thematernal uterus, where increased production of IL-1 activatesNF-B, leading to labor. We have revealed a response pathwaythat ties augmented surfactant production by the maturing fetallung to the initiation of labor. We suggest that SP-A secretedby the fetal lung serves as a hormone of parturition.
Abbreviations: SP-A, surfactant protein A; AF, amniotic fluid;Lac-Z mice, B6;129SGt(rosa)26Sor mice; i.a., intraamniotic;-gal, -galactosidase; dpc, days postcoitum; LPS, lipopolysaccharide;P4, progesterone; PR, progesterone receptor; TLR, Toll-likereceptor.
To whom correspondence should be addressed at: Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038. E-mail: cmende{at}biochem.swmed.edu.
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-gal, 
,
Julie M. Faust *, and
Carole R. Mendelson * 
B in the maternal uterus increased with the gestational increase in SP-A. SP-A stimulated IL-1
To whom correspondence should be addressed at: Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038. E-mail: 
