A Comprehensive Investigation of the Activin-family in Chorioamnionitis

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In order to study the role of activin in chorioamnionitis, we first measured activin A secretion from the cells in primary amniotic epithelia cultures. With the permission of The Internal Review Board and the informed consent of the patients, we obtained fetal membrane samples during cesarean sections, from patients with single pregnancy without systemic disease, signs of premature delivery or fetal complications. Amniotic epithelial cells were dispersed by trypsin and cultured. Both a gram negative bacterial cell wall component lipopolysaccharide and inflammatory cytokine tumor necrosis factor-alpha stimulated the secretion of activin A from the cells. Therefore, activin seemed to be involved in the pathology of chorioamnionitis. Next, to establish a system for comprehensive analysis of gene expression, we performed DNA microarray and quantitative real-time PCR analyses in a 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treated amniotic epithelial cell culture. Thirty nine TCDD-inducible genes, including CYP1A1 and CYP1B1 which are known as the typical TCDD target genes, was identified by both analyses. Furthermore, the expression of interferon-inducible genes and genes related to collagen synthesis or degradation was enhanced by TCDD. Chorioamnionitis is the primary cause of premature rapture of the membrane. On the other hand, the tensile strength of fetal membranes is provided by the collagen of amnion. Considering the biological character of the amnion and the present findings, the system established in the present study seems to be useful in the comprehensive investigation for gene expression of cytokines, including the activin-family, in chorioamnionitis.