Stimulation of embryo hatching and implantation by prostacyclin and peroxisome proliferator-activated receptor delta activation: implication in IVF.
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.
Huang
J-C
JC
Department of Obstetrics, Gynecology and Reproductive Services, The University of Texas Health Science Center, Houston, TX 77030, USA. jaou-chen.huang@uth.tmc.edu
Wun
W-S A
WS
Goldsby
J S
JS
Wun
I C
IC
Noorhasan
D
D
Wu
K K
KK
D000085:Acetates / Q000494:pharmacology; D000818:Animals; D001755:Blastocyst / Q000187:drug effects / Q000502:physiology*; D010064:Embryo Implantation / Q000187:drug effects / Q000502:physiology*; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D005307:Fertilization in Vitro; D051379:Mice; D047494:PPAR delta / Q000096:biosynthesis / Q000502:physiology*; D010636:Phenols / Q000494:pharmacology; D010642:Phenoxyacetates
C520164:4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid; D000085:Acetates; D047494:PPAR delta; D010636:Phenols; D010642:Phenoxyacetates; D011464:Epoprostenol