Expression of Cyclooxygenase Isoforms in Developing Rat Placenta, Human Term Placenta, and BeWo Human Trophoblast Model

Abstract

Cyclooxygenase (COX) catalyzes the rate-limiting step in the conversion of essential fatty acids (EFAs) to bioactive molecules such as prostaglandins (PGs), which play critical roles in many aspects of female reproduction and in fetal development. There are two primary related COX isoforms, the constitutively expressed COX-1 and the inducible COX-2. Although the expression of COX-1 and COX-2 has been demonstrated in the amnion, chorion, and decidua, relatively little information exists with regard to their expression and physiological function in the placenta during gestation. In this study, we have elucidated the spatial and temporal patterns of COX-1 and COX-2 expression in the labyrinthine and junctional zones of the developing rat placenta, in the human term placenta, and in the BeWo human trophoblast model using semiquantitative RT-PCR, Western blot, and immunohistochemical analyses. The mRNA and protein expression of COX-1 and COX-2 were demonstrated in the developing rat placenta with increasing expression observed toward parturition. COX-2 exhibited greater expression than COX-1 after mid-gestation and had a corresponding shift in spatial expression from the labyrinthine to the junctional zone at term. COX-1 and -2 were also expressed in human term placenta, while BeWo cells exhibited moderate expression of COX-1 and weak expression of COX-2. The results demonstrate that COX-1 and COX-2 are expressed in the rat and human placentas. The differential expression patterns in the rat placenta, especially of COX-2, imply that there may be gestational changes in the biosynthesis of PGs and other potential bioactive EFA metabolites. Establishing the expression of the COX isoforms provides a framework for future investigations into the functional and physiological significance of COX-1 and COX-2 in the placenta, particularly with respect to influencing normal pregnancy and fetal development, and to provide insights into therapeutic utilization of COX inhibitors in pregnancy.