Prostaglandin D2 is the major cyclooxygenase-1-derived product in prepartum mouse uteri where it mediates an enhanced in vitro myometrial contraction

Abstract

This study aimed to determine whether prostaglandin D₂ (PGD₂) is a major uterine cyclooxygenase (COX) product and if so, we wanted to examine the underlying mechanism, its relation to COX-1-mediated metabolism, and how it influences the in vitro myometrial contraction during the late stage of pregnancy. The production of PGD₂ or responses evoked by the prostanoid were determined in uteri isolated from prepartum and/or non-pregnant C57Bl/6 wild-type (WT) or COX-1^-/- mice. Results showed that PGD₂, which was not detected in non-pregnant counterparts, appears as the major prostanoid in prepartum (<24h prior to parturition) mouse uteri. No signal of PGD₂ or other COX-derived products was detected in similar tissues of COX-1^-/- mice. Western blot or real-time PCR revealed that expressions of COX-1 and PGD₂ synthase (PGDS) in prepartum uteri were higher than those of non-pregnant mice, while both were diminished by the removal of endometrium. Also, we noted that in endometrium-removed prepartum uteri PGD₂ evoked an increased contraction compared to that of non-pregnant mice. Antagonizing the F prostanoid (FP) receptor but not D prostanoid receptors abolished the contraction. Moreover, the level of FP receptor mRNAs in endometrium-removed prepartum uteri was increased compared to that of non-pregnant mice. These results imply that due to up-regulations of COX-1 and PGDS in endometrium, PGD₂ becomes the major prostanoid produced in prepartum uteri where it can evoke an increased in vitro myometrial contraction, possibly resulting from up-regulation of the FP receptor, the mediator of such a response in mouse uteri.

Keywords: COX-1; Myometrial contraction; Prepartum; Prostaglandin.