The conventional way of making babies is no secret: a father produces a sperm which, when it comes into contact with a mother’s egg, gives rise to an embryo containing genetic material from both parents. The process is popular but not universally accessible; same-sex couples cannot produce biological children together.
Scientists have therefore long sought more ambitious recipes, especially ones that remove the need for either parent. They have enjoyed some success: mice with two mothers and no fathers were reported in 2004. But creating animals with two fathers and no mother has proved much harder.
On June 23, 2025, a Chinese team presented the most complete attempt yet. In a paper published in PNAS, a journal, they report creating two healthy, fertile “bipaternal” mice, whose genetic material originates from two males.
Such an achievement is possible because each sperm cell (like a mother’s egg) contains one-half of the genetic material needed for an embryo to form. What complicates things, however, is that some parental genes come with an “imprint”, a crucial set of chemical modifications that adjust the genes’ activity.
As the maternal and paternal imprints often affect development in opposing ways, taking genetic material from two parents of the same sex risks producing unviable offspring.
To overcome this problem, scientists have tried gene-editing one of the egg and sperm cells to delete the DNA regions responsible for imprinting. This has worked for eggs, with only three or four deletions required to produce a bimaternal mouse.
But paternal imprinting is harder to overcome. In a paper published in January by another Chinese team, researchers showed that as many as 20 regions need to be deleted to produce a bipaternal mouse. Even then, the resulting individual could not naturally reproduce.
The team behind the new study, led by Wei Yanchang from Shanghai Jiao Tong University, used a technique known as epigenetic editing. Rather than directly messing with the genes, epigenetic editing targets the imprints, the tiny molecules that control the genes’ activity. Adding or removing these molecules can boost or suppress individual genes without permanently modifying the genes themselves.
The first step was to take a regular mouse egg cell and remove its nucleus, which is where the maternal DNA is contained. They then filled the empty egg with epigenetic editors, proteins designed to either add or remove epigenetic marks. The editors used in their experiments were programmed to find seven imprinted DNA regions that needed modification. Two tail-less sperm cells were then inserted into this egg, enabling them to come together and begin the development of an embryo. As only one was taken from the breed of mouse that the editors had been programmed to recognise, only that sperm cell would be modified.
Success has many fathers
Once the resulting embryo had grown large enough, the team put it into the uterus of a foster-mother mouse in the hope that a pregnancy would ensue. Out of 259 bipaternal embryos transferred into 18 mice, three living pups were born. Two developed into normal, healthy adults who were able to reproduce; one fathered nine offspring, the other six. This demonstrated for the first time that it is possible to create fertile two-father animals by rewriting paternal imprinting in the early embryo. “It is an intelligent and neat approach,” says Mahesh Sangrithi, a doctor specialising in reproductive medicine at King’s College London. That is not to say that it is efficient: only 0.8% of the transferred embryos turned into live animals.
The difficulties Dr Wei and his team encountered offer intriguing evidence for a long-standing evolutionary theory. Some biologists have proposed that a “battle of the sexes” plays out during embryonic development, wherein the fathers’ genes benefit their progeny at the expense of the mother’s future reproductive potential (which might benefit another male). In the new studies, the nonviable bipaternal pups were overgrown, suggesting that such a battle might indeed be taking place.
Of wider interest is whether epigenetic editing would allow two human fathers (or, indeed, mothers) to have a biological child on their own. As the approach avoids permanent genetic modifications, it is potentially a less risky intervention than gene editing. But don’t expect biparental human babies anytime soon. For one thing, editing the imprints in human sperm would probably be much more complex than for murine ones. For another, human embryo research is heavily regulated. Research on two-mother babies, which has had a 20-year head start, is still far from the clinic.
Other techniques, such as turning male cells into eggs, might be a more fruitful approach to the same challenge. But for the foreseeable future, biological parenthood will remain dependent on a person of each sex willing to pool their DNA.
