Cyclooxygenase-2-derived endogenous prostacyclin enhances mouse embryo hatching.

INTRODUCTION The role of prostaglandins (PGs) in embryo hatching remains controversial. In addition, there is no direct evidence that mouse embryos synthesize PGs. METHODS The effects of endogenous PG on mouse embryo hatching were evaluated by blocking endogenous PG synthesis with indomethacin. Specific cyclooxygenase (COX) inhibitors were used to identify the role of COX-1- and COX-2-derived PGs. An eicosanoid profile was generated by incubating blastocysts with [3H]arachidonic acid and analysing the metabolites by high performance liquid chromatography. The expression and the localization of COX-1, COX-2 and prostacyclin synthase (PGIS) were examined by western blot analysis and immunohistochemistry. RESULTS The hatching of embryos cultured in 30 microl of protein-free medium was blocked by indomethacin (P = 0.007) or a selective COX-2 inhibitor (P = 0.004). Adding back iloprost, a prostacyclin analogue, abolished the effects of the COX-2 inhibitor. Prostacyclin was the most abundant PG produced by mouse blastocysts, which expressed COX-1, COX-2 and PGIS. COX-1, COX-2 and PGIS were expressed in 4-cell stage embryos and beyond; they were present in the inner cell mass and the trophectoderm of the blastocysts. CONCLUSION Mouse embryos express COX-1, COX-2 and PGIS which catalyse the formation of PGI2; COX-2-derived PGI2 plays a critical role in embryo hatching.