RESUMEN
BACKGROUND: Successful IVF depends in part on quality embryos. Recent work suggests that prostaglandin I(2) (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 (PPARdelta) mediates the effects of PGI(2) at the implantation sites. METHODS: The expression of PPARdelta in the preimplantation embryos was examined by RT-PCR, western blot analysis and immunohistochemistry. Synthetic PPARdelta ligand (L-165041) and PPARdelta targeted (PPARdelta(-/-)) embryos were used to reveal the roles of PPARdelta in PGI(2)-stimulated and spontaneous embryo development. RESULTS: Preimplantation embryos express PPARdelta, 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 PPARdelta deletion. Blastocyst formation and embryo hatching were impaired in PPARdelta(-/-) embryos. PPARdelta deletion significantly reduced embryo cell proliferation (P < 0.01); PPARdelta activation increased embryo cell proliferation (P < 0.05). PPARdelta activation enhanced the implantation of wild-type (WT) embryos (P < 0.05); PPARdelta deletion reduced embryo implantation (P < 0.05). CONCLUSIONS: PPARdelta is essential for spontaneous and PGI(2)-stimulated embryo development and blastocyst hatching. The implantation of cultured embryos is enhanced by PPARdelta activation. PPARdelta represents a novel therapeutic target to improve IVF outcome.
Asunto(s)
Blastocisto/fisiología , Implantación del Embrión/fisiología , Epoprostenol/farmacología , PPAR delta/fisiología , Acetatos/farmacología , Animales , Blastocisto/efectos de los fármacos , Implantación del Embrión/efectos de los fármacos , Femenino , Fertilización In Vitro , Ratones , PPAR delta/biosíntesis , Fenoles/farmacología , FenoxiacetatosRESUMEN
BACKGROUND: Recently we discovered that the human oviduct synthesizes abundant prostacyclin (PGI(2)). Gene knock-out studies suggest that PGI(2) is essential to endometrial decidualization, but the effects of PGI(2) on sperm and embryos have not been reported. METHODS: The effects of PGI(2) on human sperm were analysed by a computer-assisted semen analysis system. The effects of PGI(2) on mouse embryos were examined based on the rates of complete hatching. The expression of PGI(2) receptor (IP) was evaluated by Western blot analysis and immunohistochemistry. The binding of PGI(2) to embryos was confirmed by radioligand binding assay. Finally, cAMP levels were assessed in PGI(2)-challenged embryos. RESULTS: Iloprost (a stable PGI(2) analogue) did not affect the motility or the overnight survivability of human sperm. Western blot analysis did not detect IP in the sperm plasma membrane. In contrast, the hatching of mouse embryos was enhanced by iloprost (ED(50) 6.7 nmol/l). Exposure to iloprost during 8-cell to morulae or morulae to early blastocyst stages was critical to enhanced hatching. This coincided with the developmental stage-specific expression of IP. Although iloprost bound to blastocysts, it did not significantly increase cAMP. CONCLUSION: PGI(2) enhanced the hatching of mouse embryos but not the motility of human sperm.