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Hum. Reprod. Advance Access published online on October 15, 2004
Human Reproduction, doi:10.1093/humrep/deh524
© 2004 by European Society of Human Reproduction and Embryology
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Received May 26, 2004
Accepted August 19, 2004

Article

Cyclooxygenase-2-derived endogenous prostacyclin enhances mouse embryo hatching

Jaou-Chen Huang 1*, W.-S.Alfred Wun 2, Jennifer S. Goldsby 1, Nena Matijevic-Aleksic 3, and Kenneth K. Wu 3

1 Department of Obstetrics and Gynecology, University of Texas Health Science Center-Houston, TX, USA
2 Obstetrical and Gynecological Associates, Houston, TX, USA
3 Vascular Biology Center, Institute of Molecular Medicine and Division of Hematology, Department of Internal Medicine, University of Texas Health Science Center-Houston, TX, USA

* To whom correspondence should be addressed. E-mail: Jaou-Chen.Huang{at}uth.tmc.edu.


  Abstract

INTRODUCTION: The role of prostaglandins (PGs) in embryo hatching remains controversial. In addition, there is no direct evidence that mouse embryos synthesize PGs. METHODS: The effects of endogenous PG on mouse embryo hatching were evaluated by blocking endogenous PG synthesis with indomethacin. Specific cyclooxygenase (COX) inhibitors were used to identify the role of COX-1- and COX-2-derived PGs. An eicosanoid profile was generated by incubating blastocysts with [3H]arachidonic acid and analysing the metabolites by high performance liquid chromatography. The expression and the localization of COX-1, COX-2 and prostacyclin synthase (PGIS) were examined by western blot analysis and immunohistochemistry. RESULTS: The hatching of embryos cultured in 30 µl of protein-free medium was blocked by indomethacin (P=0.007) or a selective COX-2 inhibitor (P=0.004). Adding back iloprost, a prostacyclin analogue, abolished the effects of the COX-2 inhibitor. Prostacyclin was the most abundant PG produced by mouse blastocysts, which expressed COX-1, COX-2 and PGIS. COX-1, COX-2 and PGIS were expressed in 4-cell stage embryos and beyond; they were present in the inner cell mass and the trophectoderm of the blastocysts. CONCLUSION: Mouse embryos express COX-1, COX-2 and PGIS which catalyse the formation of PGI2; COX-2-derived PGI2 plays a critical role in embryo hatching.

Keywords: embryo survival; embryotrophic factor; IVF; non-steroidal anti-inflammatory drugs; preimplantation embryo development.
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