New insights into the molecular endocrinology of parturition

Carole R. Mendelson, Jennifer C. Condon

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)113-119
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume93
Issue number2-5
DOIs
StatePublished - Feb 2005

Keywords

  • Fetal lung
  • Macrophage
  • Nuclear factor κB
  • Parturition
  • Surfactant protein-A

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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