Fertilization in vitro increases non-disjunction during early cleavage divisions in a mouse model system.
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.
Department of Genetics and the Center for Human Genetics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Christopher J
CJ
Bean
Terry J
TJ
Hassold
LuAnn
L
Judis
Patricia A
PA
Hunt
D000782:Aneuploidy; D000818:Animals; D020090:Chromosome Segregation / Q000502:physiology*; D002970:Cleavage Stage, Ovum / Q000502:physiology*; D004622:Embryo, Mammalian / Q000502:physiology; D005314:Embryonic and Fetal Development; D005307:Fertilization in Vitro; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009030:Mosaicism; D009630:Nondisjunction, Genetic; D010100:Oxygen / Q000378:metabolism; D014998:Y Chromosome / Q000235:genetics
D010100:Oxygen