Document Detail

Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition.
MedLine Citation:
PMID:  15044702     Owner:  NLM     Status:  MEDLINE    
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-1beta in AF macrophages and activation of NF-kappaB in the maternal uterus increased with the gestational increase in SP-A. SP-A stimulated IL-1beta and NF-kappaB 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-kappaB 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-1beta activates NF-kappaB, 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.
Jennifer C Condon; Pancharatnam Jeyasuria; Julie M Faust; Carole R Mendelson
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-03-25
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  101     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-04-07     Completed Date:  2004-06-10     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4978-83     Citation Subset:  IM    
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
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MeSH Terms
Base Sequence
DNA Primers
Interleukin-1 / genetics
Lung / embryology,  secretion*
Macrophages / metabolism
Mice, Inbred ICR
NF-kappa B / metabolism
Pulmonary Surfactant-Associated Protein A / metabolism*
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Uterine Contraction / physiology*
Uterus / cytology,  metabolism,  physiology
Grant Support
3 P01 HD11149-25S1/HD/NICHD NIH HHS; 5 P01 HD11149/HD/NICHD NIH HHS
Reg. No./Substance:
0/DNA Primers; 0/Interleukin-1; 0/NF-kappa B; 0/Pulmonary Surfactant-Associated Protein A; 0/RNA, Messenger

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