Researchers make oocytes from embryonic stem cells

By Graeme O'Neill
Thursday, 23 June, 2005

Monash University fertility researchers have succeeded in producing oocytes -- eggs -- from mouse embryonic stem (ES) cells, offering hope to couples who are unable to conceive, even by in vitro fertilisation, because the partner lacks viable eggs.

Dr Orly Lacham-Kaplan, of the university's Immunology and Stem Cell Laboratories, has developed a simple, reliable system for producing oocytes from ES cells. ES cells are totipotent -- potentially capable of producing all of the cell types that form a living animal.

An overseas research group claimed in 2003 to have shown that ES cells could spontaneously differentiate into ovarian-like tissues containing eggs, but other research groups were subsequently unable to replicate the research.

The University announced this week that Lacham-Kaplan has developed a replicable system for producing oocytes from ES cells, paradoxically, by exposing the cells to as-yet unidentified growth factors present in media conditioned by testicular cells.

Lacham-Kaplan, who announced her discovery at last week's annual conference of the European Society of Human Reproduction and Embryology in Copenhagen, said she had not yet confirmed that the oocyte-like cells were haploid.

Normal eggs and sperm contain only a single set of chromosomes; fertilisation creates a diploid cell carrying a mixture of genes from each parent.

Lacham-Kaplan said she planned to determine the chromosome complement of the ES-derived oocytes after returning to Australia.

Monash may have timed its announcement to coincide with the announcement at the Denmark conference of similar achievement by UK researchers.

Prof Harry Moore's reproductrive research group at the University of Sheffield, a leader in stem-cell research, announced on Monday it had derived primordial germ cells capable of producing either eggs or sperm, from donated human ES cells.

When cultured, some of the cells reached a later stage of differentiation into sperm, and Moore said while his team has yet to generate mature sperm, it is close to doing so.

Moore said if the technique can be perfected and proven safe -- a big "if" -- it may be possible to treat infertile people to produce their own sperm and eggs. If enough eggs were produced, it would eliminate the need for donors. It would also obviate the need for donor eggs for the still-controversial practice of therapeutic cloning for tissue and organ repair.

Lacham-Kaplan wants to find ways for infertile children to have children. "Some people just don't have eggs or sperm, and there's little we can do for them except donor material," she said.

In her experiment she cultured embryoid bodies -- clusters of ES cells -- in testicular-cell conditioned media, that transformed in seven days into ovarian-like structures containing egg follicles.

Further studies confirmed the oocyte-like cells were expressing two genes expressed exclusively in egg cells.

She said the ability to develop eggs in vitro could primarily assist infertile women, but could also be used to create a bank of eggs that could be used for somatic-cell nuclear transfer, a technique whereby the nucleus of an oocyte is removed and the nucleus of a donor somatic cell substituted.

Because the donor nucleus is genetically identical to the donor's own cells, it can be used to create ES cells that could be used as a source of 'self' cells for brain or spinal repairs, or to repair major organs.

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