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Mice bred with two mums – Expert Reaction

Press Release – Science Media Centre

Researchers from China have bred healthy mice with two mums (and no dad) that went on to have normal pups of their own.
Researchers from China have bred healthy mice with two mums (and no dad) that went on to have normal pups of their own.
The feat was achieved by altering stem cells from a female mouse and injecting them into the eggs of another. The researchers were examining what makes it so challenging for mammals of the same sex to reproduce and found that some of these barriers can be overcome using stem cells and targeted gene editing. The authors note that there are still obstacles to using these methods in other mammals.

The SMC asked New Zealand experts to comment on the study, please feel free to use these comments in your reporting. The research is available on scimex.org for registered journalists.

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Dr Tim Hore, Senior Lecturer, Department of Anatomy, University of Otago, comments:
Note: This paper directly relates to an active area of investigation in Dr Tim’s lab, which includes understanding if parent-specific gene expression can be altered by new stem cell culturing methods.

“This is an interesting paper following-up on a long-standing question of developmental biology – why is it that in mammalian newborns you need to have equal genetic contributions from both a mother and a father, whereas elsewhere in the animal kingdom, it is possible to create (for example), chickens, komodo dragons and sharks without a genetic contributions from a father?

“It turns out that mammals express some of their genes only from mother’s DNA, and some only from father’s DNA. Around 100 genes are affected by this peculiar form of parent-gene expression, and because some of the affected genes are essential for proper growth and development, you need to have DNA from both mother and father in order to create healthy mammalian offspring.”

What did the researchers do?
“The researchers in this paper used genetic modification to alter the genes which are expressed in a parent-specific manner in mammals. In doing so, they were able to artificially overcome some of the usual incompatibility between parents of the same sex, meaning they were able to create relatively healthy offspring with two-mothers, and somewhat unhealthy offspring from two fathers that died shortly after birth.”

What’s the significance?
“Mice with two mothers were created in the early 2000s (Kono et al., 2004), however, what makes this achievement unique is the range of technology used – the researchers cleverly combined gene editing and the production of stem cells from only one parent (known as ‘haploid’ stem cells). Yet, the work does fall short of creating mammalian offspring from the same sex in the absence of substantial genetic modification, meaning it is unlikely to be useful in humans – for now.

“In order for same-sex parents to both have genetic contributions to their children in an assisted reproduction setting, it is likely another technological leap will be required. One possible approach is using ‘epigenetic-editing’ on haploid stem cells, essentially reprogramming the DNA of one parent so it looks like that of the opposite sex without altering any genetic sequence.”

Conflict of interest statement: None that I am aware of.

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Dr Teresa Holm, Research Fellow, Department of Molecular Medicine and Pathology, University of Auckland comments:

“This is an important advance that builds on previous efforts to make uniparental (‘fatherless’ or motherless’) offspring using DNA from same-sex parents. Improving on prior studies, researchers from the Chinese Academy of Sciences generated uniparental mice by genetically modifying embryonic stem cells and inserting the DNA into unfertilised eggs.

This process of reproduction by same-sex parents is not normally possible in mammals due to a phenomenon known as ‘imprinting’, whereby certain genes are turned on or off depending on whether they come from the mother or father. If these ‘gene dosage’ effects are not tightly controlled it can be catastrophic for the embryo, resulting in birth defects or death.

“In this study, some of the key imprinted DNA regions were removed by gene editing, resulting in healthy female mice but males that died shortly after birth.

“The major impact of this work is the furthering of our fundamental understanding of how imprinting operates in mammals and how it acts as a barrier to uniparental reproduction.

“In the long-term, this knowledge may help researchers improve assisted reproductive technologies for infertile couples where disturbances in imprinting may contribute to the health of artificially fertilised embryos. It may even lead to the development of ways for same sex couples to reproduce healthy of their own children. However, it is important to note that the current work was carried out in mice and involved a number of genetic modifications in embryonic stem cells.

“Therefore, this kind of approach in humans carries significant ethical and safety concerns that would need to be overcome if it was to move beyond the laboratory.”

Conflict of interest statement: None declared

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Our colleagues at the Australian SMC gathered the following comments, feel free to use them in your reporting:

Robert Norman, Director of the Robinson Institute and Professor of Reproductive and Periconceptual Medicine, University of Adelaide, comments

“This is a paper that deals with fundamental questions about reproduction looking at the use of two females or two males to make an embryo and live animal. This can occur naturally in non-mammalian animals but not in more evolutionary advanced species.

“These investigators have made egg and sperm like structures from stem cells and used two females or two males to make embryos (in contrast to nature where one male and one female are used). To succeed they had to modify the chemical groups that modulate the DNA expression known as epigenetic markers.

“This approach led to a successful outcome in female-female fertilisation but less so in males. The female offspring were able to reproduce, had a longer lifespan, different cognitive and behavioural changes and some metabolic abnormalities.

“This approach is still not perfect but may lead to successful outcomes for endangered species of animals and possibly better experimental research animals.

“The concept is intriguing for human reproduction, particularly for same-sex couples but there are far too many uncertainties at present to attempt such an approach for many years to come.

“The first challenge will be to make babies from artificially derived eggs and sperm from male and female couples, an exercise that is increasingly important for infertile men and women who have no functioning gametes of their own. No ethical permission has been given anywhere to attempt to produce live offspring although embryos have been produced experimentally with no transfer to the uterus.”

Conflict of interest statement: None declared.

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