Surfactant protein-A mRNA expression by human fetal membranes is increased in histological chorioamnionitis but not is spontaneous labour at term

Surfactant protein-A (SP-A) is produced by the fetal lung, participates in innate immunity, and has been proposed to play a role in the initiation of parturition in mice. Amniotic fluid SP-A concentration increases as a function of gestational age, and SP-A protein has been demonstrated in human chorioamniotic membranes. This study was conducted to determine whether parturition at term, gestational age and chorioamnionitis in preterm delivery (PTD) are associated with changes in the expression of SP-A in the chorioamniotic membranes. Chorioamniotic membranes were obtained from women at term and women with PTD (n = 58). SP-A mRNA and protein expression was detected in amniotic epithelial cells, chorionic trophoblasts and macrophages by in situ hybridization and immunohistochemistry. Quantitative real-time reverse transcription-PCR demonstrated predominant expression of SP-A1 mRNA, whose expression was 17.4-fold higher in patients with PTD with chorioamnionitis (n = 15) than in those without (n = 13) (p = 0.018). While no difference was observed in SP-A1 mRNA expression in the chorioamniotic membranes of women at term not in labour (n = 16) and those in labour (n = 14) (p = 0.87), the expression in term membranes was higher than that of membranes from women with PTD without chorioamnionitis (p = 0.003). Analysis of JAR choriocarcinoma cells demonstrated SP-A1 mRNA expression that was up-regulated following lipopolysaccharide treatment. Furthermore, monocytic cell lines (THP-1 and U937) and peripheral blood monocytes (CD14⁺/CD115⁺) obtained from pregnant women also expressed SP-A1 mRNA and protein, suggesting the presence of autocrine/ paracrine activation in vivo. Interestingly, a mid-trimester amniotic fluid sample obtained from a case of tracheal atresia contained SP-A (3.13 μg/ml), indicating the presence of SP-A of extrapulmonary origin. These findings suggest not only that SP-A expression is a part of the innate immune response deployed during chorioamniotic inflammation, but also that chorioammotic membranes are a source of SP-A in the amniotic fluid with advancing gestation.