An adult male mouse with two fathers successfully breeds./Courtesy of Wei Yanchang

A mouse born to two fathers without a mother has succeeded in giving birth to another mouse. This is the first time that two male gametes, sperm, have combined to create a living organism that has further reproduced.

On the 24th, Professor Wei Yanchang and his research team from Shanghai Jiao Tong University in China reported that a mouse created solely from the genes of two male mice grew up and successfully gave birth. The research findings were published in the Proceedings of the National Academy of Sciences (PNAS) on the same day.

Children inherit DNA equally from both parents. The researchers created an embryo by inserting two sperm into a mouse egg from which the nucleus had been removed, eliminating its genes. This mouse inherited genes equally from the two fathers, resulting in all male offspring.

Simply mixing sperm was not sufficient for the embryo to grow properly. The researchers adjusted seven points of the genes contained in the sperm using a technique called "epigenome editing." This method controls the on-off state of the genes without altering the genes themselves.

The 259 embryos created in this way were implanted into surrogate female mice. Ultimately, only two male mice survived to adulthood and later mated with other females, producing healthy offspring. They proved normal in appearance, weight, and growth rate.

Previously, a mouse born to two mothers that could reproduce was first reported in 2004. If only the chromosomes from the mother or father are present, the problem of "genetic imprinting" could arise, causing certain genes to work excessively or not at all. At that time, Japanese researchers created the first functional mouse with two mothers, named "Kaguya," through genetic modification.

However, the fact that the Japanese researchers used two eggs at different developmental stages means it was not true asexual reproduction using only eggs without sperm. In 2022, Wei and his research team successfully reported in PNAS that they corrected specific genes in mouse eggs, enabling healthy offspring to be born through asexual reproduction.

The researchers succeeded in producing fatherless mice by regulating gene expression without altering the genetic information of DNA. In January of this year, they created adult mice with two male parents using the same method and succeeded in reproduction this time.

Research obtaining offspring using only paternal or maternal gametes could aid in the study of animal fertilization and development processes. For the same reason, it could provide useful information for infertility treatments. Theoretically, this method could also allow same-sex couples to have children with their own genes. Adjusting gene expression switches is relatively safe as it does not directly manipulate genes.

However, its application to humans is nearly impossible due to the very low success rate even in animal experiments. Thousands of eggs and numerous surrogates are needed, and the technology to create eggs from human stem cells has not yet been developed. Because humans and mice have different genetic compositions and operational mechanisms, it is still unknown if the same method would work for humans.

Christophe Gallichet, research operations manager at the Sainsbury Wellcome Centre in the UK, noted, "This research on obtaining offspring from same-sex parents is promising, but due to the number of eggs required, the number of surrogates needed, and the low success rate, it is impossible to apply to humans."

References

PNAS (2025), DOI: https://doi.org/10.1073/pnas.2425307122

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