The conditions in which embryos are cultured in the laboratory during in vitro fertilisation could be causing genetic errors that are associated with certain developmental syndromes and other abnormalities in growth and development, such as low birth weight. Researchers told the 22nd annual conference of the European Society of Human Reproduction and Embryology today (Monday) that preliminary work investigating genetic imprinting in mouse embryos had shown that certain culture media and concentrations of oxygen altered the expression of several imprinted genes.

Imprinting is the process by which some genes are activated or inactivated depending on whether they have been inherited in chromosomes from the mother or the father.

Professor Paolo F Rinaudo, a scientist at the Center for Reproductive Sciences, University of California, San Francisco, USA, said: “We found that the culture of mouse embryos in the laboratory is sufficient to alter the expression of several imprinted genes and that this effect can be modified by the composition of the culture medium and oxygen concentration.

“Interestingly, the expression of one gene, H19, was reduced regardless of the culture conditions, and as H19 is associated with Beckwith Wiedeman syndrome, this finding needs to be investigated further.”

However, he cautioned against reading too much into his results at this stage. “These studies are important for better directing future resources and studies in humans. But we must remember that these are preliminary results in a mouse model, and they need to be repeated and confirmed in other strains of mice before translating to studies in humans.”

Other research has suggested that culturing embryos in the laboratory during IVF could be affecting embryos adversely. “Emerging new evidence shows that some neurological and behavioural abnormalities are associated with assisted reproductive techniques. Cases of Angelman and Beckwith Wiedeman syndromes in humans, which are due to aberrant genomic imprinting, and other abnormalities in growth and development in mice have been described after culture in vitro,” said Professor Rinaudo. Angelman syndrome is characterised by severe mental retardation, speech impairment, balance disorder and a happy, excitable demeanour; it occurs in about one in 10,000 to 30,000 of the population. Beckwith Wiedeman syndrome is characterised by overgrowth, with an abnormally large tongue, umbilical hernia, neonatal hypoglycaemia and a predisposition to certain tumours, in particular, Wilms tumour and hepatoblastoma; it is rare, occurring in one in 36,000 of the population.

Professor Rinaudo and his colleagues cultured mouse embryos in four media with 5% oxygen. Two of the four media were also used with 20% oxygen, making six different cultures in total. As a control, some embryos were left to mature in the mice (in vivo).

“We identified 38 imprinted genes, most of which showed no difference in expression after in vitro culture compared to the in vivo embryos. Five genes showed a statistical difference compared to the in vivo control, depending on the culture conditions,” he said.

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European Society for Human Reproduction and Embryology