Self-correction of chromosomally abnormal embryos in culture and implications for stem cell production.
OBJECTIVE
To ascertain whether embryos classified by preimplantation genetic diagnosis (PGD) for infertility as abnormal and then plated to obtain stem cells would self-correct partially or totally in culture, producing disomic stem cells.


METHODS
Prospective study to determine the chromosome status of embryos on day 3 and 6, as well as cultured cells derived from inner cell masses from the same embryos when cultured up to day 12.


METHODS
Research laboratory.


METHODS
Patients undergoing PGD of aneuploidy.


METHODS
Of 142 embryos classified by PGD for aneuploidy as abnormal, 50 were cultured to the blastocyst stage. At that stage a fraction of the embryos underwent trophectoderm biopsy to reconfirm the PGD diagnosis. After further co-culture with feeders up to day 12, 34 embryos attached to the feeder cells. Of those, 24 were analyzed by fluorescence in situ hybridization (FISH) and the rest for the expression of Oct-4, SSEA-3, SSEA-4, TRA1-60, and TRA1-80.


METHODS
Disomic cells obtained from trisomic embryos.


RESULTS
Analysis by FISH of day-12 cultures showed that 7 were totally normal, 6 were mostly abnormal, and 11 had experienced some chromosome normalization, having between 21% and 88% normal cells. Day-12 culture was positive for Oct-4 expression by reverse transcriptase polymerase chain reaction analysis and for SSEA-3, SSEA-4, TRA1-60, and TRA1-80 by immunocytochemistry.


CONCLUSIONS
Chromosome self-normalization occurs in a significant proportion of chromosomally abnormal embryos, possibly because of the loss of a chromosome in trisomic cells after blastocyst stage. Thus chromosomally abnormal embryos are a potential source of disomic stem cells. Not all chromosomally abnormal embryos self-corrected. Abnormal stem cells that might be derived could be used as models to study the effect of chromosomal abnormalities on human development.
Munné
Santiago
S
Reprogenetics, LLC, West Orange, New Jersey 07052, USA. munne@embryos.net
Velilla
Esther
E
Colls
Pere
P
Garcia Bermudez
Mercedez
M
Vemuri
Mohan C
MC
Steuerwald
Nury
N
Garrisi
John
J
Cohen
Jacques
J
D002869:Chromosome Aberrations / Q000196:embryology*; D046149:Embryo Culture Techniques / Q000706:statistics & numerical data; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology*; D006801:Humans; D019836:Preimplantation Diagnosis / Q000379:methods / Q000706:statistics & numerical data; D011446:Prospective Studies; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*