TY - JOUR
T1 - New insights into the molecular endocrinology of parturition
AU - Mendelson, Carole R.
AU - Condon, Jennifer C.
N1 - Funding Information:
This research was supported by National Institutes of Health Grants 3-P01-HD11149-25S1 and 1-R01-HL078824, and by Advanced Research Program Grant 010019-0123-2001 from the Texas Higher Education Coordinating Board.
PY - 2005/2
Y1 - 2005/2
N2 - The signals that lead to the initiation of parturition have remained a mystery. We postulate that in humans and other mammals, uterine quiescence is maintained by increased progesterone receptor (PR) transcriptional activity, and spontaneous labor is initiated or facilitated by a concerted series of biochemical events that negatively impact PR function. In recent studies, we have obtained compelling evidence to suggest that the fetus signals the initiation of labor by secretion into amniotic fluid of major lung surfactant protein, SP-A. SP-A expression is developmentally regulated in fetal lung and is secreted into amniotic fluid in high concentrations near term (after 17 days postcoitum [dpc] in the mouse). We found that injection of exogenous SP-A into mouse amniotic fluid at 15 dpc caused preterm labor. SP-A activated amniotic fluid macrophages in vitro to express nuclear factor κB (NF-κB) and interleukin-1β (IL-1β). These macrophages, which are of fetal origin, migrate to the pregnant uterus causing an inflammatory response and increased uterine NF-κB activity. We suggest that the increase in NF-κB within the maternal uterus both directly increases expression of genes that promote uterine contractility and negatively impacts the capacity of the PR to maintain uterine quiescence, contributing to the onset of labor. Our findings, therefore, indicate that SP-A secreted into amniotic fluid by the maturing fetal lung serves as a hormone of parturition.
AB - The signals that lead to the initiation of parturition have remained a mystery. We postulate that in humans and other mammals, uterine quiescence is maintained by increased progesterone receptor (PR) transcriptional activity, and spontaneous labor is initiated or facilitated by a concerted series of biochemical events that negatively impact PR function. In recent studies, we have obtained compelling evidence to suggest that the fetus signals the initiation of labor by secretion into amniotic fluid of major lung surfactant protein, SP-A. SP-A expression is developmentally regulated in fetal lung and is secreted into amniotic fluid in high concentrations near term (after 17 days postcoitum [dpc] in the mouse). We found that injection of exogenous SP-A into mouse amniotic fluid at 15 dpc caused preterm labor. SP-A activated amniotic fluid macrophages in vitro to express nuclear factor κB (NF-κB) and interleukin-1β (IL-1β). These macrophages, which are of fetal origin, migrate to the pregnant uterus causing an inflammatory response and increased uterine NF-κB activity. We suggest that the increase in NF-κB within the maternal uterus both directly increases expression of genes that promote uterine contractility and negatively impacts the capacity of the PR to maintain uterine quiescence, contributing to the onset of labor. Our findings, therefore, indicate that SP-A secreted into amniotic fluid by the maturing fetal lung serves as a hormone of parturition.
KW - Fetal lung
KW - Macrophage
KW - Nuclear factor κB
KW - Parturition
KW - Surfactant protein-A
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U2 - 10.1016/j.jsbmb.2004.12.027
DO - 10.1016/j.jsbmb.2004.12.027
M3 - Article
C2 - 15860253
AN - SCOPUS:18044377611
SN - 0960-0760
VL - 93
SP - 113
EP - 119
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
IS - 2-5
ER -