US scientists reprogram cells to produce mice from 2 male parents

http://www.lifescientist.com.au/article/370797/us_researchers_breed_mice_from_two_males/?fp=4194304&fpid=1

US researchers breed mice from two males stem cells
David Binning (Australian Life Scientist) 09 December, 2010 17:36

It’s been something of a holy grail amongst reproductive scientists for some time; the breeding of animals with same sex parents.

However, reports today by U.S researchers of the successful breeding of mice from two fathers have been met with caution by Australian scientists and legal experts.

“Whilst the findings in this paper are intriguing, whether such an approach could ever be applied to human reproduction is highly unlikely,” said Dr Megan Munsie, Senior Manager, Research and Government, Australian Stem Cell Centre.

“The mice were not born simply from two fathers. Rather they were created by a complex process dependent on access to foetal tissue, the creation of stem cells, additional embryos, surrogate mothers and natural mating.”

“Leaving aside the practicalities of applying such a convoluted process to create a human baby, there are significant safety, ethical and legal considerations that prevent its application. The real value of pluripotent stem cell research lies with increasing our understanding of normal development and disease.”

So what exactly did the researchers do?

Dr. Richard R. Berhringer at the M.D. Anderson Cancer Center in Texas and his team manipulated fibroblasts from a male (XY) mouse foetus to produce an induced pluripotent stem cell (iPS) cell line. Something like one percent of iPS cell colonies grown from this XY cell line lost the Y chromosome for some reason, thereby producing XO cells.

These XO iPS cells were then injected into blastocysts taken from donor female mice. The treated blastocysts were then transplanted into surrogate mothers, which gave birth to female XO/XX chimeras having one X chromosome from the original male mouse fibroblast. The female chimeras, carrying oocytes derived from the XO cells, were mated with normal male mice. Some of the offspring were male and female mice that had genetic contributions from two fathers.

“Our study exploits iPS cell technologies to combine the alleles from two males to generate male and female progeny, i.e. a new form of mammalian reproduction.” the authors said.

“It is also possible that one male could produce both oocytes and sperm for self-fertilization to generate male and female progeny,” the scientists point out.

They added that it may also be possible in future to generate human oocytes from male iPS cells in vitro. Incorporated as part of in vitro fertilization, there would be no need for female XO/XX chimeras, however a surrogate mother would nevertheless still be required to carry the two-father pregnancy to term. Using a variation of the iPS technique, the researchers say “it may also be possible to generate sperm from a female donor and produce viable male and female progeny with two mothers.”

The study appears in the current issue of the journal Biology of Reproduction.

No doubt it will lead to enthusiastic debate about the possibility for same sex couples wishing for offspring combing their own genetic material. The authors also suggest that it might lead to better techniques for improving livestock, as well as for saving endangered species, especially in cases where females are scarce or non-existent.

But the researchers themselves acknowledge that there would need to be a significant refinement of the science before any such applications could even be considered. Indeed, for Australian scientists, this is something of an understatement.

According to associate Professor Kuldip Sidhu, director of the Stem Cell Lab and Chair of Stem Cell Biology at the University of New South Wales, his and other research labs around the world have produced data which points to the possibility of same sex reproduction, but the reality of this for humans is some way off, if it is even feasible at all.

“With the emergence of induced pluripotent stem cell technology, it is now possible to understand many complex biological processes like reproduction rapidly which otherwise is not possible or feasible because of ethical constraints,” he said.

“Previously it has been demonstrated in many laboratories including our group, that the embryonic stem cells derived from embryos, and induced pluripotent stem cells produced from adult cells from the body of males or females, have the equal potentials to produce male and female germ cells in the Petri dish under appropriate culture conditions i.e. male stem cells can produce female germ cells and vice versa.”

“This current research may seem very tantalising for same sex couples but you still need females to incubate the embryos for live birth and also the XO stem cells clones are generally not viable unlike in mice. Some of the projections in this paper on humans are a bit farfetched as yet.”

Furthermore, in many countries, including Australia, there are significant legal barriers.

‘The new research may lead same sex couples, both male and female, to hope that same sex couples may one day be able to have a child who is genetically related to both of them,” said Professor Loane Skene, Professor of Law at the University of Melbourne and former Deputy Chair of the Lockhart Committee on human cloning and embryo research.

‘The new research may lead same sex couples, both male and female, to hope that same sex couples may one day be able to have a child who is genetically related to both of them. “However, even if such a technique was possible in humans, it could not lawfully occur in Australia under the current law. Federal and state legislation prohibits the combination of DNA from more than two people in forming an embryo, and implanting an embryo formed for research into a woman.”