Surfactant protein-A (SP-A) selectively inhibits prostaglandin F (PGF) production in term decidua: Implications for the onset of labor

Victoria V. Snegovskikh, Vineet Bhandari, Jo Rae Wright, Serkalem Tadesse, Thomas Morgan, Colin MacNeill, Nastaran Foyouzi, Joong Shin Park, Yuguang Wang, Errol R. Norwitz

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Context: Labor is characterized by "decidual activation" with production of inflammatory mediators. Recent data suggest that surfactant protein-A (SP-A) may be critical to the onset of labor in mice. Whether this is also true in humans is unclear. Objectives: The aim was to investigate: 1) the expression of SP-A at the maternal-fetal interface; 2) the effect of SP-A on the production of inflammatory mediators by human decidua; and 3) the association between single nucleotide polymorphisms in maternal SP-A genes and spontaneous preterm birth. Research Design and Methods: In situ expression of SP-A was investigated by immunohistochemistry and quantitative RT-PCR. Term decidual stromal cells were isolated, purified, and treated with/without SP-A (1-100 μg/ml), IL-1β, and/or thrombin. Levels of inflammatory mediators [IL-6, IL-8, TNFα, matrix metalloproteinase-3, monocyte chemotactic protein-1, IL-1β, PGE2, prostaglandin F2α (PGF2α)] and angiogenic factors (soluble fms-like tyrosine kinase-1, vascular endothelial growth factor) were measured in conditioned supernatant by ELISA and corrected for protein content. The effect of SP-A on eicosanoid gene expression was measured by quantitative RT-PCR. Results: SP-A localized to endometrium/decidua. High-dose SP-A (100 μg/ml) inhibited PGF2α by term decidual stromal cells without affecting the production of other inflammatory mediators,and this effect occurred at a posttranscriptional level. Decidual SP-A expression decreased significantly with labor. Single nucleotide polymorphisms in the SP-A genes do not appear to be associated with preterm birth. Conclusions: SP-A is produced by human endometrium/decidua, where it significantly and selectively inhibits PGF2α production. Its expression decreases with labor. These novel observations suggest that decidual SP-A likely plays a critical role in regulating prostaglandin production within the uterus, culminating at term in decidual activation and the onset of labor.

Original languageEnglish (US)
Pages (from-to)E624-E632
JournalJournal of Clinical Endocrinology and Metabolism
Issue number4
StatePublished - Apr 2011

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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