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Hum. Reprod. Advance Access published online on September 30, 2005
Human Reproduction, doi:10.1093/humrep/dei286
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© The Author 2005. 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@oupjournals.org

Article

Adverse effects of retinoic acid on embryo development and the selective expression of retinoic acid receptors in mouse blastocysts

Fu-Jen Huang 1*, Yan-Der Hsuuw 2, Kou-Chung Lan 3, Hong-Yo Kang 1, Shiuh-Young Chang 1, Yu-Cheng Hsu 3, and Ko-En Huang 1

1 Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Chang Gung University School of Medicine
2 Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Animal Science, National Ping-Tung University of Science Technology
3 Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan

* To whom correspondence should be addressed.
Fu-Jen Huang, E-mail: huangfj{at}seed.net.tw


  Abstract

BACKGROUND: All-trans retinoic acid (RA), the oxidative metabolite of vitamin A, is essential for normal development. In addition, high levels of RA are teratogenic in many species. We have previously shown that excess RA results in immediate effects on the preimplantation embryo and on blastocyst development. This study was conducted to clarify the long-term survival of mouse blastocyst and the effect of RA on gene expression. METHODS AND RESULTS: Using an in vitro model, we identified the immediate adverse impact of RA on mouse blastocyst development. This involved an inhibition of cell proliferation and growth retardation. Using an in vivo model, we also identified the resorption of post-implanted blastocysts that had been treated with excess RA. Analysis of RA-mediated gene induction was also included. The retinoic acid receptors RAR{alpha} and RAR{gamma} were constitutively expressed in the blastocyst and the inner cell mass, whereas RAR{beta} was induced upon RA treatment. CONCLUSIONS: This is the first evidence to show the impacts of RA on mouse blastocysts in vitro and any carry-over effects in the uterus. There is a retardation of early postimplantation blastocyst development and then subsequent blastocyst death. Our findings also show that there is some degree of selective induction of retinoic acid receptors when excess RA is administered to the blastocysts.

Keywords: blastocyst/embryo development/retinoic acid/retinoic acid receptor.
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