The first mouse with two biological fathers has survived until adulthood, a new study has revealed.
Researchers from the Chinese Academy of Sciences say they have succeeded in breeding mice using only genetic material from two males.
Through a technique called 'embryonic stem cell engineering’, scientists created eggs from the sperm of one father which could be fertilised by the other.
The stem cell technique used by the researchers is not entirely new, but all previous attempts faced seemingly insurmountable problems.
Mice bred using two sets of male genes either failed to grow at all or were born with severe developmental defects that prevented them from reaching adulthood.
However, by editing 20 different genes in the mice's stem cells, the researchers were able to prevent these issues.
Co-author of the study Dr Wei Li says: 'This work will help to address a number of limitations in stem cell and regenerative medicine research.'
While it is currently only possible in mice, this major breakthrough could pave the way for gay men to have children who are biologically related to both fathers.
Researchers have successfully bred a mouse (right) that has two male parents (one pictured left) and can survive to adulthood by editing their genes to overcome developmental challenges
In order to breed offspring which have two biological fathers, the researchers first needed to transform the male sex cells from one parent into female sex cells.
The scientists took sperm from a mouse and injected it into a type of cell called an oocyte - an immature egg cell that has had its genetic material removed in a process called enucleation.
This created a stem cell - a type of cell with the potential to become any other type of cell in the body - which contained only male DNA from the first parent.
The researchers then took one of these stem cells and a sperm cell from another male and injected both into another enucleated immature egg.
These male cells combined to create an embryonic stem cell containing the DNA of both parents, which was then used to create an embryo which could be implanted in a surrogate mother.
Once the embryo had developed, the mother gave birth to the offspring, which contained only genetic material from the two males.
Scientists have known for a long time that this is possible and have managed to create viable embryos using the technique.
However, no one has previously managed to create 'bi-paternal' mice that are actually capable of surviving to adulthood.
By changing genes which control how the parents' chromosomes combine, the bi-paternal mice lived much longer and could even survive weaning. Edited mice are shown by the dark blue line
How was the mouse created?
- Scientists take sperm from a mouse and inject it into a cell called an oocyte - an immature egg cell that has had its genetic material removed in a process called enucleation.
- This creates a stem cell - a type of cell with the potential to become any other type of cell in the body.
- Researchers then take one of these stem cells and a sperm cell from another male and inject both into another enucleated immature egg.
- These male cells combine to create an embryonic stem cell containing the DNA of both parents, which is then used to create an embryo which can be implanted into a surrogate mother.
- Once the embryo develops, the mother gives birth to the offspring, which contains only genetic material from the two males.
During heterosexual reproduction, genetic material from a male carried by the sperm combines with genetic material from a female contained in the egg, or ovum.
When this happens, a group of genes called 'homologous chromosomes' from the mother come together with those from the father and combine in a process called 'crossing over'.
But when both sets of homologous chromosomes come from either two males or two females, the genes don't copy over properly, leading to 'imprinting abnormalities'.
These abnormalities can cause developmental defects which prevent the offspring from living healthy lives.
Co-author Dr Qi Zhou says: 'The unique characteristics of imprinting genes have led scientists to believe that they are a fundamental barrier to unisexual reproduction in mammals.
'Even when constructing bi-maternal or bi-paternal embryos artificially, they fail to develop properly, and they stall at some point during development due to these genes.'
In this study, the researchers used a gene editing technology called CRISPR to make changes to mice's DNA in order to prevent imprinting abnormalities.
After creating stem cells from the first male's sperm, they inserted or removed sections of genetic code at 20 places in the mice's DNA that control imprinting.
Using a technique called CRISPR, the researchers modified 20 genes in one of the male mice. This prevented their offspring developing defects which led to earlier death (stock image)
When these genetically modified stem cells were combined with the sperm from another male, they were much more likely to develop properly.
These changes resulted in mice with two fathers who were able to live until adulthood for the first time ever.
Study co-author Dr Guan-Zheng Luo, of Sun Yat-sen University in Guangzhou, says: 'These findings provide strong evidence that imprinting abnormalities are the main barrier to mammalian unisexual reproduction.
'This approach can significantly improve the developmental outcomes of embryonic stem cells and cloned animals, paving a promising path for the advancement of regenerative medicine.'
The authors do acknowledge some significant limitations to these findings.
Only 11.8 per cent of the viable embryos were capable of developing to birth and not every pup which was born lived to adulthood.
The mice that did live to adulthood showed altered growth, shortened lifespans, and were sterile.
However, these results show the first promising steps towards giving gay men the option to have children who are related to both of their fathers.
In the future, the development of this technique could allow gay men to have children who are genetically related to both partners. However, gene editing techniques are currently not permitted for use on humans (stock image)
In theory, it could be possible to use a similar technique to create an embryo using stem cells derived from one human partner and sperm from the other.
Although the child would still need to be carried to term by a female surrogate, they would have genetic material only from both of their fathers.
Currently, the researchers are planning to try this approach in larger animals like monkeys - and warn that the technological hurdles will be significantly larger.
That means getting the technique to work in humans could require years of effort.
However, not everyone is convinced that scientists should try to pursue this technology in humans, even if it is possible.
Lukasz Konieczka, executive director of the LGBT+ charity Mosaic Trust, told MailOnline: ''I do understand that some might have a strong desire to have biological children as it offers some virtual immortality, as psychologists call it.
'I do not think it is necessary to spend time and resources on such technology as we still have children who are alive today, stuck in a care system due to neglectful or abusive biological parents.'
Since the technique requires editing the genome of the parent's stem cells, it is also prohibited in humans.
The International Society for Stem Cell Research's ethical guidelines for stem cell research do not allow heritable genome editing for reproductive purposes nor the use of human stem cell-derived gametes for reproduction because they are deemed as currently unsafe.
WHAT ARE INTERNATIONAL LAWS ON USING HUMAN EMBRYOS IN SCIENTIFIC RESEARCH?
European Union
Since 1984, the European Union has provided funding for scientific research through a series of framework programs for research and technological development.
This include providing funding for research using embryonic stem cells as well as a human embryonic stem cell registery, which began operations in April 2007 in order to make more efficient use of pre-existing embryonic stem cell lines.
More recently, a legal battle over whether stem cell techniques can be patented may alter the research landscape, as the removal of the legal protections provided by the patent system might greatly dampen incentives for stem cell research in the EU
United Kingdom
In the UK, the law states that the use of embryos in stem cell research can only be carried out with authority from the Human Fertilisation and Embryo Authority (HFEA).
Licences are only granted if the HFEA is satisfied that any proposed use of embryos is absolutely necessary for the purposes of the research.
Research is allowed only in the following conditions:
- To promote advances in the treatment of infertility
- To increase knowledge about the causes of congenital disease
- To increase knowledge about the causes of miscarriages.
- To develop more effective techniques of contraception.
- To develop methods for detecting the presence of gene or chromosome abnormalities.
- To increase knowledge about the development of embryos.
- To increase knowledge about serious disease.
- To enable any such knowledge to be applied in developing treatments for serious disease.
United States
State laws regarding embryonic stem cells vary widely, with some restricting their use and others permitting certain activities.
Approaches to stem cell research policy range from statutes in eight states—California, Connecticut, Illinois, Iowa, Maryland, Massachusetts, New Jersey and New York— which encourage embryonic stem cell research, to South Dakota's law, which strictly forbids research on embryos regardless of their source.
States that specifically permit embryonic stem cell research have established guidelines for scientists such as consent requirements and approval and review processes for projects.
In Massachusetts, for example, experiments can be performed on embryos that have not experienced more than 14 days of development.