Why does cloning create abnormalities?

Significant abnormalities observed in cloned mice help reinforce the need to continue to avoid the reproductive cloning of humans, claims Dr Takumi Takeuchi, from Cornell University.

He and Dr Gianpiero Palermo's team have compared imprinting abnormalities (the process where specific genes inherited from both parents are silent) in mice embryos derived from assisted reproduction techniques and from cloning and they found significantly impaired development in the cloned embryos compared with those derived from more conventional ART techniques.

Drs Takeuchi and Palermo were prompted to undertake the research by concerns about the increased incidence of imprinting abnormalities in children born after ARTs. The most prominent of these is Beckwith-Wiedemann syndrome, where children are born larger than normal.

Scientists also knew that cloned animals had been born with a similar condition, called 'large offspring syndrome'. Dr Takeuchi's team set out to study whether the disorders arising in the ART system and those in cloned animals were comparable. The team took mouse oocytes and divided them into three groups. 68 were inseminated by ICSI, 37 activated parthenogenetically (without involving male gametes), and 77 were cloned by injecting a cell nucleus into an egg where the nucleus had been removed. Of this latter group, 43 underwent first embryonic cleavage (the first few divisions of an embryonic egg), and 15 became full blastocysts.

The embryos created by parthenogenesis and those from ICSI reached the blastocyst stage at the same rate, unlike the clones, where only 30% got that far. This appears to be due to the abnormal gene expression seen in the cloned group. This not only explains the developmental impairment of the cloned group, but may in future be helpful in identifying environmental culture conditions that are deleterious to the development of ART embryos.

Dr Takeuchi said that as yet it was difficult to make a direct link with a specific cause for the abnormalities. "But there are a number of possibilities," he said. "They could be linked to fertility medications utilised to induce superovulation, or the progesterone employed to help implantation; in vitro culture conditions which could be related to the length of the culture or the concentrations of certain media components such as serum or even a specific amino acid. Finally, we cannot exclude the contribution of the peculiar genetic makeup of patients' gametes, together with the specific ART procedure," he said.

Identification of gene expression abnormalities would help to monitor the development of reproductive techniques prior to their application to routine medical practice, said Dr Takeuchi.