For the first time, mice born to two fathers have grown up and produced offspring, scientists in China have revealed.

The researchers at Shanghai Jiao Tong University managed to insert two sperm cells – one from each father – into a mouse egg whose nucleus had been removed.

A gene editing technique was then used to reprogram parts of the sperm DNA to allow an embryo to develop – a process called androgenesis.

The embryo, featuring the genetic material from two fathers, was transferred to a female womb and allowed to grow to term.

Finally, the resulting offspring (male) managed to grow to adulthood and become a parent after mating conventionally with a female.

In their lab experiments, the researchers managed to successfully demonstrate the method twice – birthing two fertile male mice, both with two fathers.

The promising breakthrough could pave the way for two gay men to have a child of their own who can also go on to have a family.

However, experts have cautioned that there is still a way to go before any such procedures are attempted in humans.

These adult male mice, which each have the genetic material of their two fathers, have gone on to have offspring of their own

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‘In this study, we report the generation of fertile androgenetic mice,’ the Chinese experts say in their paper, published in the journal PNAS.

‘Our findings, together with previous achievements of uniparental reproduction in mammals, support previous speculation that genomic imprinting is the fundamental barrier to the full-term development of uniparental mammalian embryos.’

Experts caution that we are not ready to start such experiments in humans, which could be deeply unethical.

Christophe Galichet, research operations manager at the Sainsbury Wellcome Centre in London, points out that the success rate of the experiments was very low.

Of 259 mice embryos that were transferred to female mice, just two survived, grew to adulthood and then fathered their own offspring.

‘This research on generating offspring from same-sex parents is promising,’ Galichet, who was not involved with the experiments, told New Scientist.

‘[But] it is unthinkable to translate it to humans due to the large number of eggs required, the high number of surrogate women needed and the low success rate.’

Today, gay couples who want to have children usually rely on a surrogate mother or father to bring a child into the world.

Today, gay couples who want to have children usually rely on a surrogate mother or father to bring a child into the world (file photo)

How did the scientists do it? Experts took sperm from two male mice and injected it into an immature egg cell with its genetic material removed (known as enucleation) Gene editing was then used to reprogram seven parts of the sperm DNA to allow an embryo to develop The embryo, featuring the genetic material from two fathers, was transferred to a female womb and allowed to grow to term The offspring grew to adulthood and became a parent after mating with a member of the opposite sex These offspring appeared normal in terms of size, weight, appearance

Unlike with a pair of heterosexual parents, this means that one of the couple is not actually related to the child. So it’s long been a dream for gay couples to raise a child who has genetic material from both fathers (or both mothers).

Back in 2023, researchers revealed they’d been able to create mice from two biological fathers for the first time.

Because mice are actually genetically very similar to us, the promising results hinted the feat could be replicable in humans.

But even if a human child could be birthed from two fathers, it potentially threw a huge ethical quandary into the mix: What if that human child is not able to have children of their own through normal conception when they reach adulthood?

Fortunately, these new experiments suggest this might not be an issue.

The human related to both of his or her fathers would grow up and be able to have a family of their own, the results suggest.

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’.

A gene editing technique was then used to reprogram parts of the sperm DNA to allow an embryo to develop – a process called androgenesis (file photo)

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’ and developmental defects.

That’s why the researchers had to turn to gene editing, which makes tweaks in the DNA, and target genes responsible for imprinting.

Researchers are also considering this approach in larger animals like monkeys – but the technological hurdles will be significantly larger.

Dr Helen O’Neill, molecular geneticist at the University College London, called the new work a ‘major step forward’.

‘It confirms that genomic imprinting is the main barrier to uniparental reproduction in mammals and shows it can be overcome,’ she told New Scientist.

Earlier this year, another Chinese team got mice with two fathers to grow to adulthood by editing 20 different genes in their stem cells, but the rodents weren’t fertile.

We’re a step closer to two men being able to have genetic children of their own after the creation of fertile mice by putting two sperm cells in an empty egg

Adult male mice that have two fathers and went on to have offspring of their own Yanchang Wei

For the first time, mice with two fathers have gone on to have offspring of their own – marking a significant step towards enabling two men to have children to whom they are both genetically related. However, there is still a long way to go before this could be attempted in people.

Yanchang Wei at Shanghai Jiao Tong University in China achieved the feat by putting two sperm cells together in an egg whose nucleus had been removed. The team then used a method called epigenome editing to reprogram seven sites in the sperm DNA, which was needed to allow the embryo to develop.

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Of the 259 of these embryos that were transferred to female mice, just two offspring – both male – survived and grew to adulthood, making the success rate very low. Both then fathered offspring – which appeared normal in terms of size, weight and appearance – after mating with females.

Creating mice with two fathers has proved to be much harder than creating mice with two mothers. The birth of the first fertile mouse with two mothers, Kaguya, was reported in 2004.

Kaguya had to be genetically modified, but in 2022, Wei and his colleagues were able to create similarly fatherless mice using only epigenome editing, which doesn’t alter the DNA sequence. This same method was used to make the motherless mice.

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The reason it is such a significant feat to create mammals with two fathers or two mothers is due to a phenomenon called imprinting, which is related to the fact that most animals have two sets of chromosomes, one inherited from the mother and one from the father.

During the formation of eggs and sperm, chemical labels are added to these chromosomes that program some genes to be active and others to be inactive. These changes are called “epigenetic” because they don’t change the underlying DNA sequence, but the labels can still be passed on when cells divide, meaning their effects can last a lifetime.

Crucially, epigenetic programming in mothers is different from that in fathers, with some genes that are labelled as “on” in sperm being labelled as “off” in eggs, and vice versa.

This means that if an egg has two sets of maternal chromosomes, or two sets of paternal ones, it cannot develop normally. A gene that should be active in one chromosome of a pair may be turned off in both, or both copies of a gene may be active when only one should be, resulting in an “overdose” of that gene.

In Kaguya’s case, researchers got around this by deleting part of a gene to make overall gene activity more normal. But creating mice with two fathers requires many more changes.

Earlier this year, a separate team in China got a few mice with two fathers to grow to adulthood after making 20 genetic modifications to normalise their gene activity, but these mice weren’t fully healthy or fertile.

While correcting gene activity via genetic modification is useful for studying imprinting in lab animals, it would be unacceptable in people, not least because the effects of the genetic changes aren’t fully understood.

For their epigenetic approach, Wei and his team used modified forms of the CRISPR proteins that are usually used for gene editing. Just like standard CRISPR proteins, these can be made to seek out specific sites on genomes. But when these sequences are found, the modified proteins add or remove epigenetic labels rather than altering DNA.

The study is a major step forward, says Helen O’Neill at University College London. “It confirms that genomic imprinting is the main barrier to uniparental reproduction in mammals and shows it can be overcome.”

Because it doesn’t involve genetic modification, the epigenome-editing approach could, in principle, be used to allow same-sex couples to have genetic children of their own. However, the success rate would need to be much higher before the technique could be considered for use in people. “While this research on generating offspring from same-sex parents is promising, it is unthinkable to translate it to humans due to the large number of eggs required, the high number of surrogate women needed and the low success rate,” says Christophe Galichet at the Sainsbury Wellcome Centre in the UK.

There are several reasons why the success rate was so low. For starters, combining two sperm cells means a quarter of the embryos had two Y chromosomes and wouldn’t have developed far. Also, the epigenome editing only worked at all seven sites in a small proportion of the embryos, and it might have had off-target effects in some cases.

The success rate and health of the animals could probably be improved by altering more than seven sites. Another issue is that in people a slightly different set of sites might need altering.

If human babies with two fathers are ever created in this way, they would technically be three-parent babies because the mitochondria in their cells, which contain a tiny amount of DNA, would come from the egg donor.

In 2023, a team in Japan announced the birth of mouse pups with two fathers using a third technique that involves turning mouse stem cells into eggs. However, it isn’t clear if any pups survived to adulthood, and so far no one has managed to turn human stem cells into eggs.

At the Third International Summit on Human Genome Editing, held in March 2023 at the Francis Crick Institute in London, Japanese researcher Katsuhiko Hayashi stunned attendees when he explained how he had successfully reproduced mice from two male parents.

In effect, Hayashi had developed a complex procedure for turning male pluripotent (meaning embryonic or inducible) stem cells into female stem cells, allowing him to obtain eggs from a male. His surprising findings were published in the journal Nature a few weeks later.

Almost two years later, a team of Chinese researchers – led by Zhi-kun Li, Wei Li and Qi Zhou of the Chinese Academy of Sciences – has once again shocked the field of genetics with a similar procedure.

However, these scientists found a completely different way of achieving the same result. They produced a baby mouse from two males without maternal biological intervention, beyond needing a female mouse to gestate the embryos generated. Their results were published last month in the journal Cell Stem Cell.

This new procedure developed by Li and colleagues combats a mammalian control system called genetic imprinting, which prevents viable mammal embryos from being obtained by combining two gametes of the same sex (two sperm or two eggs). These embryos do not survive naturally, since in mammals every embryo has to derive from a male gamete (sperm) and a female gamete (egg).

The reason for this is that some genes are only expressed if they are inherited from the mother, while others have to be inherited from the father. And all of them are essential for survival.

The Chinese researchers’ highly complex process manages to convert, after numerous steps, a spermatozoa into a cell that behaves like an egg cell. They did this by deactivating the imprinting barrier, which is found at twenty points in the genome, through gene editing with CRISPR tools. This cell (now with the genetic characteristics of an egg) can be combined with another spermatozoa to create a viable mouse embryo. That embryo is gestated by a mouse, and the mice that are born are derived from two sperm, from two fathers, without the genetic involvement of eggs, or a mother.

Issues remain

This process is still not without problems. As the study’s authors acknowledge, the mice created by this process are not fertile, and can only be reproduced through cloning.

Additionally, more than half of the mice born to two fathers either do not survive, die young, fail to mature properly, or fail to reach adulthood.

In a previous study from 2018, the same research team had shown that mice born to two mothers were fertile and survived longer than those born to two fathers, all of whom died shortly after birth. In their new study, published last month, the results have improved, though only partially.

Could we apply this technique to humans?

Though these experimental studies were conducted on mice, they raise the question of whether such procedures could ever safely produce human embryos, and what impact this would have.

This is not yet possible, though if it were, it would revolutionise fertility treatments. Male same-sex couples, for instance, could both be the biological parents of their children – one would provide sperm and the other would provide pluripotent stem cells which, following either of the two procedures (that of the Japanese or the Chinese researchers), would produce eggs that could be fertilised in vitro and gestated by a woman through surrogacy. Surrogacy is illegal across much of the EU, but permitted in other countries.

Similarly, a female same-sex couple could also have biological children, where one contributes eggs and the other pluripotent stem cells that end up producing sperm. Either of the two women could gestate the resulting embryo, and the children born would be the biological children of both mothers.

For the moment, these human applications remain in the realm of science fiction – they are not yet technically possible, and it would be unwise to try to implement them. However, assuming that all these processes will be optimised to the point where we can consider offering them in fertility clinics, I believe it is important to reflect on this. We must ask ourselves, as a society, whether we would be willing to ethically and legally accept these techniques.

A version of this article was originally published in Science Media Centre España.

In a groundbreaking experiment, researchers from the Chinese Academy of Sciences (CAS) have successfully created a bi-paternal mouse—a mouse with two biological fathers. This marks the first time a mammal has been born from two male parents and survived into adulthood. The study, published in Cell Stem Cell on January 28, unveils a new method of genetic editing that bypasses previous barriers in same-sex reproduction.

The Genetic Roadblock of Same-Sex Reproduction

For decades, scientists have attempted to produce mammals using only two male or two female parents, but fundamental genetic obstacles made success impossible. The key issue lies in genomic imprinting, a process where certain genes are turned on or off depending on whether they come from the mother or the father.

In a normal embryo, this balance ensures proper development. However, when both sets of chromosomes originate from the same sex, this genetic harmony is disrupted, leading to severe developmental defects.

Previous attempts at creating bi-paternal mice used stem cells derived from male mice to produce egg-like cells, which were then fertilized with sperm. However, embryos created this way either failed to develop or exhibited severe abnormalities.

One of the adult bipaternal mice obtained (left). Credits: Li et al. Cell Stem Cell, 2025

A Revolutionary Approach Using CRISPR

Instead of trying to create functional eggs from male cells, the research team took a completely different approach. They identified 20 critical imprinting genes that act as roadblocks to same-sex reproduction and used the CRISPR gene-editing tool to modify these genes.

Here’s how the experiment worked:

Scientists took stem cells from a male mouse and genetically altered them to remove certain imprinted genes. These modified cells were combined with sperm from another male mouse. The genetic material was then injected into an egg cell that had been stripped of its original nucleus. The resulting embryos were implanted into a surrogate female mouse.

The result? Some of these embryos developed into live mice—a feat that was previously thought to be biologically impossible.

Genetic imprinting process carried out during the study. Credits: Li et al. Cell Stem Cell, 2025

The First Bi-paternal Mice: Life, but with Limits

Although the experiment was successful in producing live offspring, the results were far from perfect. Only 11.8% of the embryos survived to birth, and many of the mice that made it to adulthood exhibited abnormal growth and a shortened lifespan.

Interestingly, a 2004 study had previously demonstrated that bi-maternal mice (mice born from two mothers) were smaller and lived longer than normal. In contrast, the bi-paternal mice in the current study grew larger but had a significantly shorter lifespan. This suggests that paternal and maternal genes play different roles in regulating growth and longevity.

The Future of Unisexual Reproduction in Mammals

While this breakthrough does not mean human same-sex reproduction is around the corner, it offers valuable insights into embryonic development, genetic imprinting, and cloning. Researchers plan to refine the technique and apply it to larger mammals, such as monkeys, to better understand its potential.

The long-term implications of this study could extend beyond reproduction. By mastering imprinting gene modifications, scientists could enhance stem cell therapies, improve cloning techniques, and even push the boundaries of synthetic biology.

For now, the world’s first bi-paternal mouse stands as a remarkable testament to what is possible when science challenges the limits of nature.

Source: Nature

In a scientific breakthrough that challenges the very foundations of reproductive biology, Chinese researchers have successfully bred mice using genetic material from two male parents—and the offspring survived to adulthood. This pioneering experiment marks a major step in genetic engineering, with potential implications for fertility science, gene therapy, and even future reproductive possibilities in humans.

The study, published in the journal Cell Stem Cell, showcases an innovative method that manipulates imprinting genes, a crucial factor in reproduction that normally prevents mammals from developing without both maternal and paternal genetic input. By making 20 precise genetic modifications, researchers were able to overcome these barriers and create healthy, bipaternal mice. While the technique is still far from being applicable in humans, it raises profound scientific and ethical questions about the future of reproduction.

Rewriting the Rules of Reproduction

Mammalian reproduction typically requires genetic contributions from both a mother and a father due to genomic imprinting, a biological process that ensures the correct activation of certain genes. Without it, embryos with two male or two female parents struggle to develop normally, often failing to survive.

In this study, scientists identified 20 crucial imprinting genes that needed to be modified in order for bi-paternal embryos to develop successfully. These genes regulate which genetic instructions are turned on or off during development, and their improper activation had previously made bipaternal reproduction impossible in mammals.

According to study co-lead author Zhi-kun Li, an associate professor at the Chinese Academy of Sciences in Beijing:

“Our approach directly targets imprinted genes, which have long been suspected to play a central role in bi-paternal reproductive barriers,” complicating the challenge of generating offspring with two male parents.

By precisely tweaking these imprinting genes, the researchers were able to bypass the natural reproductive barriers, allowing them to create genetically healthy bipaternal mice for the first time.

A Complex Genetic Process That Took Years to Perfect

The team’s approach differed from previous attempts to create bipaternal mice. Instead of directly modifying sperm cells, researchers removed the genetic material from an immature egg and replaced it with modified embryonic stem cells derived from a male mouse. This was then fertilized using sperm from a second male, bypassing the need for maternal DNA entirely.

The experiment was not without challenges. In earlier trials, the bipaternal embryos either failed to survive past birth or exhibited severe developmental defects, such as enlarged organs, umbilical hernias, and growth abnormalities. However, by methodically testing and refining their approach, the team made key adjustments that allowed the mice to develop normally and reach adulthood.

“Our next steps include refining the gene-editing approach to produce healthier bi-paternal animals,” Li said.

While the bipaternal mice did exhibit some health issues, including shorter lifespans and infertility, their survival into adulthood represents a major step forward in reproductive genetics. Future refinements could correct these remaining challenges, potentially leading to healthier offspring.

Could This Be Applied to Humans?

Although this research is a landmark achievement, it remains far from being applicable to humans. The genetic and ethical challenges surrounding human reproduction make direct application unlikely in the near future.

The imprinting process in humans is even more complex than in mice, meaning that significant additional research would be needed before this technique could be considered for use in human fertility treatments. Additionally, the ethical considerations of gene-editing in human reproduction would need to be carefully examined before such experiments could even be considered.

That said, this research could have far-reaching implications beyond bipaternal reproduction. Understanding and modifying imprinting genes could lead to breakthroughs in fertility treatments, genetic disease prevention, and even regenerative medicine.

As scientists continue to explore the possibilities of gene-editing technology, the ability to overcome reproductive barriers may become a key frontier in medical science. While the idea of bipaternal human reproduction remains speculative, the findings from this experiment are a testament to the power of genetic engineering—and a glimpse into the future of biology.