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Hum. Reprod. Advance Access originally published online on November 17, 2006
Human Reproduction 2007 22(3):807-814; doi:10.1093/humrep/del429
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

J.-C. Huang1,5, W.-S.A. Wun2, J.S. Goldsby1,3, I.C. Wun1, D. Noorhasan1 and K.K. Wu3,4

1 Department of Obstetrics, Gynecology and Reproductive Services 2 Obstetrical and Gynecological Associates and 3 Vascular Biology Research Center and Division of Hematology, The University of Texas Health Science Center at Houston, Houston, TX, USA

4 Present address: National Health Research Institutes, No. 35, Keyan Road 350 Zhunan Town, Miaoli County Taiwan, R.O.C.

5 To whom correspondence should be addressed at: Department of Obstetrics, Gynecology and Reproductive Services, The University of Texas Health Science Center at Houston, 6431 Fannin, Houston, TX 77030, USA. E-mail: jaou-chen.huang{at}uth.tmc.edu or National Health Research Institutes, No. 35, Keyan Road 350 Zhunan Town, Miaoli County Taiwan, R.O.C. E-mail: kkgo{at}nhri.org.tw

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 {delta} (PPAR{delta}) mediates the effects of PGI2 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 PGI2-stimulated and spontaneous embryo development. RESULTS: Preimplantation embryos express PPAR{delta}, 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 PPAR{delta} deletion. Blastocyst formation and embryo hatching were impaired in PPAR{delta}–/– embryos. PPAR{delta} 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); PPAR{delta} deletion reduced embryo implantation (P < 0.05). CONCLUSIONS: PPAR{delta} is essential for spontaneous and PGI2-stimulated embryo development and blastocyst hatching. The implantation of cultured embryos is enhanced by PPAR{delta} activation. PPAR{delta} represents a novel therapeutic target to improve IVF outcome.

Key words: peroxisome proliferator activated receptor {delta}/prostacyclin/implantation/IVF/embryo culture

Submitted on July 24, 2006; resubmitted on September 26, 2006; accepted on October 5, 2006.


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J.-C. Huang, W.-S. A. Wun, J. S. Goldsby, K. Egan, G. A. FitzGerald, and K. K. Wu
Prostacyclin receptor signaling and early embryo development in the mouse
Hum. Reprod., November 1, 2007; 22(11): 2851 - 2856.
[Abstract] [Full Text] [PDF]


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