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PNAS 101 (14): 4978-4983

Copyright © 2004 by the National Academy of Sciences.


Medical Sciences

Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition

Jennifer C. Condon *, Pancharatnam Jeyasuria {dagger}, Julie M. Faust *, and Carole R. Mendelson * {ddagger} §

Departments of *Biochemistry, {ddagger}Obstetrics and Gynecology, and {dagger}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 embryo is sufficiently mature to survive outside the womb. It has been postulated that the signal for the initiation of parturition arises from the fetus although the nature and source of this signal remain obscure. Herein, we provide evidence that this signal originates from the maturing fetal lung. In the mouse, secretion of the major lung surfactant protein, surfactant protein A (SP-A), was first detected in amniotic fluid (AF) at 17 days postcoitum, rising progressively to term (19 days postcoitum). Expression of IL-1{beta} in AF macrophages and activation of NF-{kappa}B in the maternal uterus increased with the gestational increase in SP-A. SP-A stimulated IL-1{beta} and NF-{kappa}B expression in cultured AF macrophages. Studies using Rosa 26 Lac-Z (B6;129S-Gt(rosa)26Sor) (Lac-Z) mice revealed that fetal AF macrophages migrate to the uterus with the gestational increase in AF SP-A. Intraamniotic (i.a.) injection of SP-A caused preterm delivery of fetuses within 6-24 h. By contrast, injection of an SP-A antibody or NF-{kappa}B inhibitor into AF delayed labor by >24 h. We propose that augmented production of SP-A by the fetal lung near term causes activation and migration of fetal AF macrophages to the maternal uterus, where increased production of IL-1{beta} activates NF-{kappa}B, leading to labor. We have revealed a response pathway that ties augmented surfactant production by the maturing fetal lung to the initiation of labor. We suggest that SP-A secreted by the fetal lung serves as a hormone of parturition.

Key Words: surfactant protein-A • macrophage • uterus • NF-{kappa}B • labor


Abbreviations: SP-A, surfactant protein A; AF, amniotic fluid; Lac-Z mice, B6;129SGt(rosa)26Sor mice; i.a., intraamniotic; {beta}-gal, {beta}-galactosidase; dpc, days postcoitum; LPS, lipopolysaccharide; P4, progesterone; PR, progesterone receptor; TLR, Toll-like receptor.

§ 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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