Identification of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible genes in human amniotic epithelial cells

Human amniotic epithelial cells were dispersed by trypsin from amniotic membranes and cultured in DME/Ham's F12 medium supplemented with 10% FBS. Two weeks after plating, cells were treated with 50 nM TCDD or DMSO (control), further incubated for 48 hrs, and the gene expression was analyzed by DNA microarray technology and quantitative real-time PCR.Thirty eight TCDD-inducible genes, including cytochromeP4501A1 and cytochromeP4501B1, were identified. One of the remarkable profiles of the gene expression was the prominent up-regulation of interferon-inducible genes. The genes involved in the interferon gene expression and interferon signaling pathways were also up-regulated. Furthermore, the expression of genes related to collagen synthesis or degradation was enhanced by TCDD.Using DNA microarray and quantitative real-time PCR analyses, we identified TCDD-inducible genes, including interferon-inducible genes and genes related to collagen synthesis or degradation, in human amniotic epithelial cells.Exposure to dioxins causes a diverse spectrum of toxicities in humans and laboratory animals [1-4]. The fetus is one of the most sensitive targets of dioxins and a broad range of pathophysiological abnormalities, such as, disorders of brain development, thyroxin resistance, hepatic damage, hematopoietic disorders and lung dysfunction, are observed in humans after perinatal exposure to dioxins [1]. Dioxins are transferred to fetuses and infants through placentas and milk from mothers [5]. Dioxins were detected in all of the samples analyzed in a study performed using human umbilical cord or cord serum in Japan [6]. Higher dioxin levels were reported in the placenta compared to that in breast milk, in a study performed in Taiwan [7]. Not only the morphological and functional disorders brought about by the altered gene products but the comprehensive analyses of the change in gene expression are required to evaluate the effects of fetal exposure to endocrine disruptors [8]. How