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Human Reproduction, Vol. 17, No. 9, 2362-2367, September 2002
© 2002 European Society of Human Reproduction and Embryology

Fertilization in vitro increases non-disjunction during early cleavage divisions in a mouse model system

Christopher J. Bean, Terry J. Hassold, LuAnn Judis and Patricia A. Hunt1

Department of Genetics and the Center for Human Genetics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, USA

BACKGROUND: We have been studying an unusual mouse—the BALB/cWt (Wt) male—in which the Y chromosome is susceptible to high rates of mitotic non-disjunction, particularly at the first two cleavage divisions. As these are the same divisions that human embryos generated through assisted reproductive technology must complete in an artificial setting, analysis of the Wt Y chromosome allows us to examine the effect of fertilization and culture in vitro on mammalian chromosome segregation. METHODS: We performed standard mouse IVF, cultured embryos in 5% CO2 in air or in a lowered oxygen atmosphere, and used fluorescence in-situ hybridization to examine the sex chromosome constitutions of 2-, 4-, 8- and 16-cell stage Wt Y-bearing embryos. RESULTS: We observed a significant increase in mosaic sex chromosome aneuploidy at each embryonic stage in embryos cultured in 5% CO2 in air, but under lowered oxygen conditions mosaicism returned to control (in-vivo) levels. CONCLUSIONS: Our results demonstrate that slight alterations in in-vitro conditions may have a considerable impact on the genetic quality of assisted reproductive technology-derived embryos and suggest that the genetic quality of embryos should be a fundamental concern in the development of new culture systems for clinical use.

Key words: fertilization in-vitro/non-disjunction/preimplantation embryo/Y chromosome

1 To whom correspondence should be addressed at: Department of Genetics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA. E-mail: pah13{at}po.cwru.edu


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