title: Surfactant protein-A (SP-A) selectively inhibits prostaglandin F2alpha (PGF2alpha) production in term decidua: implications for the onset of labor.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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, PGE(2), prostaglandin F(2α) (PGF(2α))] 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 PGF(2α) 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 PGF(2α) 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.
authors.affiliation: Departments of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Victoria V
authors.initials: VV
authors.lastname: Snegovskikh
authors.forename: Vineet
authors.initials: V
authors.lastname: Bhandari
authors.forename: Jo Rae
authors.initials: JR
authors.lastname: Wright
authors.forename: Serkalem
authors.initials: S
authors.lastname: Tadesse
authors.forename: Thomas
authors.initials: T
authors.lastname: Morgan
authors.forename: Colin
authors.initials: C
authors.lastname: Macneill
authors.forename: Nastaran
authors.initials: N
authors.lastname: Foyouzi
authors.forename: Joong Shin
authors.initials: JS
authors.lastname: Park
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Wang
authors.forename: Errol R
authors.initials: ER
authors.lastname: Norwitz
mesh_terms: D016022:Case-Control Studies; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003656:Decidua / Q000187:drug effects* / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007745:Labor Onset / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D047929:Term Birth / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; D015237:Dinoprost