Stimulation of embryo hatching and implantation by prostacyclin and peroxisome proliferator-activated receptor δ activation: implication in IVF

BACKGROUND: Successful IVF depends in part on quality embryos. Recent work suggests that prostaglandin I2 (PGI2 or prostacyclin) promotes the development of embryos in vitro and enhances their implantation potential. The mechanism underlying the effects of PGI2 is unclear. It has been reported that peroxisome proliferator-activated receptor δ (PPARδ) mediates the effects of PGI2 at the implantation sites. METHODS: The expression of PPARδ in the preimplantation embryos was examined by RT–PCR, western blot analysis and immunohistochemistry. Synthetic PPARδ ligand (L-165041) and PPARδ targeted (PPARδ−/−) embryos were used to reveal the roles of PPARδ in PGI2-stimulated and spontaneous embryo development. RESULTS: Preimplantation embryos express PPARδ, which is essential for the enhancing effect of PGI2 and the spontaneous progression of preimplantation embryos. Enhanced blastocyst hatching by PGI2 (P < 0.05) was abrogated by PPARδ deletion. Blastocyst formation and embryo hatching were impaired in PPARδ−/− embryos. PPARδ deletion significantly reduced embryo cell proliferation (P < 0.01); PPARδ activation increased embryo cell proliferation (P < 0.05). PPARδ activation enhanced the implantation of wild-type (WT) embryos (P < 0.05); PPARδ deletion reduced embryo implantation (P < 0.05). CONCLUSIONS: PPARδ is essential for spontaneous and PGI2-stimulated embryo development and blastocyst hatching. The implantation of cultured embryos is enhanced by PPARδ activation. PPARδ represents a novel therapeutic target to improve IVF outcome.