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Human Reproduction, Vol. 18, No. 1, 130-136, January 2003
© 2003 European Society of Human Reproduction and Embryology

Retinoic acid decreases the viability of mouse blastocysts in vitro

Fu-Jen Huang1,2, Chung-Chang Shen1, Shiuh-Young Chang1,2, Tsung-Chieh J. Wu4 and Yan-Der Hsuuw1,3,5

1 Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, 2 Chang Gung University School of Medicine, 3 Department of Nutrition and Health Science, Fooyin Institute of Technology and 4 Department of Obstetrics and Gynecology, UCLA School of Medicine, California, USA 5 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, 123, Ta-Pei Rd., Niao-Sung Hsiang, Kaohsiung County, Taiwan. e-mail: s10d1{at}mail.st1917.com.tw

BACKGROUND: This study was designed to examine the cytotoxic effect of retinoic acid on the blastocyst stage of mouse embryos and on subsequent early postimplantation embryo development in vitro. METHODS AND RESULTS: Mouse blastocysts were exposed for 24 h to doses of 0, 0.1 µmol/l and 10 µmol/l all-trans retinoic acid and observed for their capacity to implant and develop during the early postimplantation period in vitro. When retinoic acid-pretreated blastocysts were allowed to implant in vitro, significantly fewer embryos were able to reach a later stage of embryo development. Compared with the findings for the control blastocysts, exposure to retinoic acid resulted in a significant reduction in the average number of total cells in blastocysts and the trophectoderm/inner cell mass lineage. The effect was associated with a significant increase in the frequency of cells identified as being engaged in apoptosis by means of the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling and Annexin V techniques. CONCLUSIONS: This is the first evidence that retinoic acid induces cell death (apoptosis) and inhibits cell proliferation in mouse blastocysts. This results in the retardation of early postimplantation blastocyst development and subsequent blastocyst death.

Key words: apoptosis/blastocyst/implantation/postimplantation/retinoic acid


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