Preeclampsia is associated with altered placental production of several end-products of cyclooxygenase activity. Thromboxane (TX) is one of these end-products, and trophoblast is a source of villous thromboxane. We cultured term trophoblast in the presence or absence of fibrin to study how differentiation and epithelial-matrix interactions regulate cyclooxygenase expression. The cellular trophoblast present during the first 24 h of culture on uncoated plastic produced TXB2, but little or no TX was produced in cultures grown longer than 24 h when differentiation into syncytial trophoblast occurred. Growth of cells on a fibrin matrix enhanced cellular trophoblast TX production five-fold. Medium containing 10 μmol/l arachidonic acid maximized thromboxane production in cells cultured for less than 24 h, regardless of growth surface, but this medium had little or no effect on TX production by cultures grown for more than 24 h. In contrast, exogenous arachidonic acid enhanced prostaglandin E2 (PGE2) production by both cellular and syncytial trophoblast. Cytochemical staining indicated that changes in cyclooxygenase content occurred with trophoblast differentiation. Western immunoblot analysis of cells cultured in the presence or absence of a fibrin matrix showed cyclooxygenase was induced under both growth conditions. Detectable cyclooxygenase protein disappeared beyond 24 h in cells grown on uncoated plastic. In contrast, cells grown beyond 24 h on fibrin showed sustained expression of cyclooxygenase by Western immunoblotting, and this enzyme protein expression correlated with increased PGE2 production by the differentiated trophoblast. These studies indicate (a) cellular trophoblast produces TX, (b) syncytial trophoblast produces PGE2 but little or no TX, (c) trophoblast-matrix interactions increase TX production, and (d) expression of cyclooxygenase is regulated during trophoblast differentiation in vitro and is modulated by a fibrin matrix. Altered in vitro placental TX production in preeclampsia may result from a response of cellular trophoblast to the increased fibrin deposition typical of placentas from preeclamptic women.
|Number of pages||7|
|Journal||Prostaglandins, Leukotrienes and Essential Fatty Acids|
|State||Published - Jan 1995|