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Hum. Reprod. Advance Access published online on July 27, 2006
Human Reproduction, doi:10.1093/humrep/del255
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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
Received February 16, 2006
Revised May 22, 2006
Accepted May 27, 2006

Article

Ginkgolide B induces apoptosis and developmental injury in mouse embryonic stem cells and blastocysts

Wen-Hsiung Chan 1 *

1 Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li, Taiwan

* To whom correspondence should be addressed.
Wen-Hsiung Chan, E-mail: whchan{at}cycu.edu.tw


  Abstract

BACKGROUND: Ginkgolide B, the major active component of Ginkgo biloba extracts, can both stimulate and inhibit apoptotic signalling. We previously showed that ginkgolide treatment of mouse blastocysts induces apoptosis, decreases cell numbers, retards early post-implantation blastocyst development and increases early-stage blastocyst death. Here, we report more detailed examinations of the cytotoxic effects of ginkgolide B on mouse embryonic stem cells (ESCs) and blastocysts and their subsequent development in vitro and in vivo. METHODS AND RESULTS: Using cell culture assay model, we revealed in our results that ginkgolide B treatment of ESCs (ESC-B5) induced apoptosis via reactive oxygen species (ROS) generation, c-Jun N-terminal kinase (JNK) activation, loss of mitochon-drial membrane potential (MMP) and the activation of caspase-3. Furthermore, an in vitro assay model showed that ginkgolide B treatment inhibited cell proliferation and growth in mouse blastocysts. Finally, an in vivo model showed that treatment with 10 µM ginkgolide B caused resorption of post-implantation blastocysts and fetal weight loss. CONCLUSIONS: Our results reveal for the first time that ginkgolide B retards the proliferation and development of mouse ESCs and blastocysts in vitro and causes developmental injury in vivo.

Keywords: apoptosis/blastocysts/development/ginkgolide B/stem cell.
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