Copenhagen, Denmark: Early embryos with abnormal chromosomes are capable of returning to normal when grown in culture in the laboratory, according to new research presented to the 21st annual conference of the European Society of Human Reproduction and Embryology today (Monday 20 June).
While such embryos are not capable of developing into normal foetuses if implanted in a woman’s womb, the discovery has important implications for stem cell production, especially in countries where the creation of embryos for stem cell research is discouraged or even banned.
Dr Santiago Munné, Director of Reprogenetics, West Orange, New Jersey, USA, told the conference: “Embryos that will not implant or are predestined to miscarry because of chromosome abnormalities, may be a source of more ethically or politically acceptable stem cells because the abnormal cells may self-correct if grown in the laboratory. In addition, stem cells derived from embryos that did not self-correct could be used to study the effect of various chromosomal abnormalities on human development.”
Dr Munné took 50 embryos, which preimplantation genetic diagnosis (PGD) had classified as abnormal at the third day of their development, and grew them in culture to the blastocyst stage when the embryonic cells start to differentiate. They were checked on day five to confirm the original diagnosis of chromosome abnormality, and continued to grow to day 12 when 34 of the embryos had succeeded in attaching to the feeder cells in the culture.
Dr Munné said: “Analysis at this stage showed that seven embryos were totally normal, six were mostly abnormal, and 11 had experienced some chromosome normalization, having between 21-88% normal cells. One embryo was tested for, and proved to show, expression of the OCT4 gene, which is essential for the survival of embryonic stem cells and primordial germ cells1.”
Good quality, normal embryonic stem cells were obtained initially from one of the normalised cultures, and more are being developed. So far no stem cells from completely abnormal embryos have been developed.
Although the mechanism by which the embryos self-corrected their abnormalities was not clear, Dr Munné believed that it probably happened when a trisomic embryo (one with three of a particular chromosome instead of the usual two) lost the third chromosome somewhere between the time that the fertilised egg first started to divide and the blastocyst stage. “However, not all the embryos were trisomic. Some had other abnormalities, namely chaotic mosaics, with all the cells abnormal but each one different from the others. These did not produce stem cells,” said Dr Munné. “It is impossible to tell at this stage which embryos are capable of self-correcting and which are not.”
Dr Munné’s findings offer researchers an opportunity to research early embryonic development and stem cells without embryos needing to be specially created for the purpose. The embryos he used would have been discarded by couples seeking fertility treatment, after PGD showed that there were abnormalities that meant the embryos would either fail to implant, or spontaneously abort at some point in the pregnancy, or would result in the birth of a child with one of the defects that the couple were trying to avoid by having PGD in the first place.
“The use of human embryos or their purposeful creation for stem cell research has been controversial, and a ban on research using government funds has been in effect in the USA since 2001. These findings offer scientists the chance to continue their research in this important field, without having to create embryos especially for the purpose,” said Dr Munné.
From European Society for Human Reproduction and Embryology