Tissue-Specific Induction of COX-2 and Prostaglandins in Lipopolysaccharide-Stimulated Extraplacental Human Gestational Membranes in a 2-Chamber Transwell Culture System

The current study investigates tissue-specific prostaglandin secretion and cyclooxygenase 2 (COX-2) induction in full-thickness human gestational membranes. Gestational membranes were collected from healthy, nonlaboring cesarean deliveries at 37 to 39 weeks gestation and cultured in 2-chamber Transwell devices. Lipopolysaccharide exposure (100 ng/mL for 8 hours) elevated prostaglandin E₂ and F_2α concentrations in the amniotic chamber medium regardless of whether exposure was to the amniotic, decidual, or both sides of the membranes. However, prostaglandin E₂ and F_{2 α} concentrations in the decidual chamber medium were elevated compared with controls only if the decidual side was exposed directly to lipopolysaccharide. Whereas prostaglandin F_2α concentrations increased to similar extents in the amniotic and decidual chambers regardless of lipopolysaccharide exposure modality, prostaglandin E₂ concentrations were 22-fold higher on the amniotic side than the decidual side after lipopolysaccharide stimulation of the amnion. These findings demonstrate the propagation of prostaglandins, prostaglandin precursors, or other factors in the direction of the decidua to the amnion, but the reverse situation was not evident. Immunostaining for COX-2 was related to the side of lipopolysaccharide exposure, that is, exposure to the amnion caused immunostaining in cells of the collagen layers of the amnion and chorion, whereas exposure to the decidual side caused staining in decidual cells. These findings suggest that the inflammatory effect of lipopolysaccharide on COX-2 induction occurs within a localized area of exposure and that prostaglandins or their precursors move across the tissues of the gestational membranes by currently undefined transport mechanisms.