Mouse ES cell advance welcomed

A US research team's demonstration that mouse embryonic stem (ES) cells can give rise to apparently normal egg cells in culture provides a "potentially superb" model for studying normal egg development and maturation in mammals, according to a Monash University stem cell expert.

Assoc Prof Martin Pera, of the Institute of Reproduction and Development at Monash Medical Centre, said the development, published last week in the international journal Science, appeared to offer, "at the very least", a model for investigating gene expression during egg development.

Dr Hans Scholer's research team at Center for Animal Transgenesis and Germ Cell Research at the University of Pennsylvania, in Philadelphia, reported evidence that cultured mouse ES cells are actually totipotent.

Previously, researchers had considered ES cells to be merely pluripotent: capable of giving rise to the entire repertoire of cell types in the mammalian body, with the exception of sex cells -- eggs and sperm -- which carry only half the complement of chromosomes required to give rise to new individuals.

At conception, the union of egg and sperm restores the full complement of chromosomes required for the development of a new individual.

The Philadelphia study, led by Dr Karin Huebner, showed that mouse ES cells grown in culture can develop into oogonia that then enter meiosis and recruit surrounding cells to form follicle-like structures that protect and nourish eggs in normal ovaries.

Huebner and her colleagues believe that oogenesis in culture should contribute to studies of nuclear transfer, manipulation of the germline, and should advance studies on fertility treatment and germ and somatic cell interaction and differentiation.

Pera said that "if it turns out that the eggs are normal, and are capable of producing normal offspring, if would be a very powerful experimental model.

"If we could achieve same thing using human ES cells, it would be an superb laboratory tool for studying how eggs develop in human females, and investigating what can go wrong in that process. It would be an outstanding tool for investigating the causes of female infertility.

"All sorts of defects can occur during the maturation process, and in the interactions between the egg and the surrounding cells in the ovary that support its development. Basic things can also go wrong in early embryonic development that trace to the egg."

But Pera cautioned against unwarranted speculation about the significance of the development, such as the suggestion that it might one day be possible to use the technique as a source of eggs for direct use in human in vitro fertilisation programs.

"That would be neither sensible nor desirable from a medical and biological viewpoint," he said.

The number of lines from which such eggs could be derived would be quite limited, so the offspring from each line would be genetically related: "you wouldn't use only half a dozen egg lines derived from ES cells, any more than you would use half a dozen sperm donors for the Australia-wide IVF program," Pera said.

And despite speculation that males could be produced from embryonic stem cells without female involvement, it was highly unlikely that this would be attempted -- even though there were examples in nature, and from the laboratory, of eggs carrying both an X and a Y chromosome, abnormalities arising from sex-specific gene imprinting, or from problems during meiosis, would almost certainly render any resulting embryos non-viable.

Asked whether scientific and media speculation about such unlikely experiments was harmful to the reputation of stem cell research, Pera said some of the "more drastic scenarios" were fuelled by people or groups fundamentally opposed to stem-cell research -- there were no good medical or biological reasons for conducting such experiments.

Pera said he believed several Australian stem cell research centres were likely to attempt to replicate the US results in the near future. "They'd certainly be interested - reproductive biology is one of our great research strengths here in Australia, and if we can get such a model to work, we'd certainly want to have it to hand," he said.