Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition.
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.
Condon
Jennifer C
JC
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jeyasuria
Pancharatnam
P
Faust
Julie M
JM
Mendelson
Carole R
CR
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000235:genetics; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014590:Uterine Contraction / Q000502:physiology*; D014599:Uterus / Q000166:cytology / Q000378:metabolism / Q000502:physiology
D017931:DNA Primers; D007375:Interleukin-1; D016328:NF-kappa B; D037662:Pulmonary Surfactant-Associated Protein A; D012333:RNA, Messenger