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"Same sex mice have pups": simple headline masks complexity of science

12 October 2018
Simple headlines can mask complex research and associated ethical issues.
Reproduction in mammals is complex and requires the inheritance of a set of chromosomes from a mother and a father.

In their new study published in Cell Stem Cell, Dr Qi Zhou and colleagues from the Chinese Academy of Sciences challenge this notion through employing a complicated combination of gene editing, stem cells and reproductive technologies.  

They showed that it was possible to create what appears to be normal mice using the genetic material from two mothers. Using a similar, but slightly more complex process, they also created pups from two fathers but these died within days of birth and others had significant abnormalities. 

Associate Professor Megan Munsie, Head of Engagement, Ethics and Policy at Stem Cells Australia notes the high level of genetic manipulation required to achieve the pups. “To create the mice, the researchers used mouse embryonic stem cells that contained only a single set of chromosomes (haploid) rather than the pairs that are usually present in mouse cells. They then deleted several regions of the genome (three different regions in the female, and seven regions in the male stem cells) to create stem cells where imprinting was erased.” Imprinting is process where the eggs and sperm have a different yet complementary pattern of coding that controls gene expression during early development.

“It is likely that a different combination of genes will need to be manipulated to allow normal development for each species, with a high cost to pay if the ‘wrong’ genes are manipulated” says Associate Professor Munsie. 

“Being able to routinely make mice and other mammals from same sex parents remain extremely challenging and significant refinements will need to be made to avoid growth abnormalities and other complications.”

Moreover, large numbers of surrogates and donors of eggs and embryos were used in these experiments, especially for the attempts using male same sex parents. 

A/Prof Munsie commented, “Creating offspring using this new approach requires genetic material and gametes from far more than two parents, raising questions about feasibility.”

Professor Bob Williamson, Chair of the Board of Stem Cells Australia commented, “While it’s easy to joke about this or think of its attractiveness to same sex couple, the research still has to be shown to be safe. In Australia, there are both legal prohibitions and ethics committees that would ensure these techniques could not be used for human reproduction.  The experiments are, however, important, because they may shine a light on some causes of serious handicap in children.”

This paper is a timely reminder of the power of technology to explore how development and inheritance is controlled, as well as the need to discuss the potential impacts of technology on society, even when at such a preliminary stage.

“We need to pause and evaluate under what circumstances, if any, the technology should be applied and, if so, to whom. Simple headlines about being able to create young from same sex parents fails to fully capture the complexity and challenges ahead”, concluded A/Prof Munsie.

Read how Qi Zhou and colleagues created the pups:

Pups from two females
To create pups from two mothers, DNA from modified female stem cells, which contained only one copy of each chromosome (haploid), rather than the normal two (diploid), were injected into normal eggs (from another mouse) to create embryos. These when transferred to a surrogate mouse, so they could develop. The success was very low, with 210 embryos creating only 29 pups. 

Pups from two males
To create pups from two fathers, the process was technically more complicated. Again, Qi Zhou and colleagues modified male stem cells to become haploid and injected these, alongside sperm from another mouse, into eggs where the female chromosomes had been removed. The resulting embryos were then allowed to develop in the lab for several days. Transferring these cells to surrogates, as with the method for females, did not work. 

For the pups to grow, the researchers needed to first obtain stem cells from the embryos and then combine these with other altered embryos, that could only contribute to the placental tissue. Using this extremely complicated route produced two live pups from almost 500 transferred embryos and both died within 48 hours of birth.