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 12 (PGI(2) or prostacyclin) promotes the development of embryos in vitro and enhances their implantation potential. The mechanism underlying the effects of PGI(2) is Unclear. It has been reported that peroxisome proliferator-activated receptor delta (PPAR delta) mediates the effects of PGI(2) at the implantation sites. METHODS: The expression of PPAR delta in the preimplantation embryos was examined by RT-PCR, western blot analysis and immunohistochemistry. Synthetic PPAR delta ligand (L-165041) and PPAR delta targeted (PPAR delta(-/-)) embryos were used to reveal the roles of PPAR delta in PGI(2)-stimulated and spontaneous embryo development. RESULTS: Preimplantation embryos express PPARS, which is essential for the enhancing effect of PGI(2) and the spontaneous progression of preimplantation embryos. Enhanced blastocyst hatching by PGI(2) (P < 0.05) was abrogated by PPAR delta deletion. Blastocyst formation and embryo hatching were impaired in PPAR delta(-/-) embryos. PPARS deletion significantly reduced embryo cell proliferation (P < 0.01); PPAR delta activation increased embryo cell proliferation (P < 0.05). PPAR delta activation enhanced the implantation of wild-type (WT) embryos (P < 0.05); PPARS deletion reduced embryo implantation (P < 0.05). CONCLUSIONS: PPAR delta is essential for spontaneous and PGI(2)-stimulated embryo development and blastocyst hatching. The implantation of cultured embryos is enhanced by PPAR delta activation. PPARS represents a novel therapeutic target to improve IVF outcome.