Using cutting-edge stem cell technology, a team of scientists from the Chinese Academy of Sciences (CAS) recently created a mouse with two biological fathers.
The research, published on January 28, 2025, in the journal Cell Stem Cell, details how scientists targeted a specific set of reproductive genes to produce a healthy, bi-paternal mouse that lived to adulthood.
In the animal kingdom, unisexual reproduction—reproduction without needing both male and female genetic material, is common for many different species of animals. A common form of this is parthenogenesis, where an embryo develops from an unfertilized egg. This occurs naturally in some reptiles, amphibians, fish, and even certain insects. For example, Komodo dragons, whiptail lizards, and some species of sharks are capable of reproducing without male fertilization under specific conditions.
Reproductive Barriers
In contrast, mammals have strict genetic imprinting mechanisms that make unisexual reproduction extremely difficult. Unlike reptiles and fish, mammals require a precise balance of maternal and paternal genetic contributions for normal development. This is due to imprinting genes, which control how certain traits are expressed and ensure that some genes are only active when inherited from a specific parent.
When these imprinting patterns are disrupted, it can lead to severe developmental abnormalities or prevent embryonic development altogether.
“The unique characteristics of imprinting genes have led scientists to believe that they are a fundamental barrier to unisexual reproduction in mammals,” Qi Zhou, one of the study’s lead authors, explained in a recent statement.
Overcoming Genetic Imprinting Issues
The research team used advanced genetic engineering techniques to modify 20 key imprinting genes to create the bi-paternal mice. They applied methods such as gene deletions and regulatory edits to correct imprinting abnormalities. As a result, they were able to produce embryos from male cells that were then fertilized with sperm from another male.
“These findings provide strong evidence that imprinting abnormalities are the main barrier to mammalian unisexual reproduction,” co-corresponding author Guan-Zheng Luo of Sun Yat-sen University in Guangzhou said. “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.”
These embryos had a significantly higher success rate compared to previous attempts, and some even survived to adulthood. While the process was not perfect—only about 11.8% of embryos developed into live mice, and many exhibited altered growth and shorter lifespans—the achievement marks a major step forward in understanding mammalian reproduction.
Bigger Ethical Considerations
This study has profound implications for stem cell research and regenerative medicine. By better understanding imprinting genes, scientists may improve techniques for cloning and tissue regeneration. However, significant challenges remain. The bi-paternal mice that reached adulthood were sterile, meaning they could not reproduce naturally.
The researchers hope that further modifications to imprinting genes could one day allow bi-paternal mammals to produce viable gametes (sperm or eggs). They also plan to explore whether their approach can be applied to animals like monkeys.
“Further modifications to the imprinting genes could potentially facilitate the generation of healthy bi-paternal mice capable of producing viable gametes and lead to new therapeutic strategies for imprinting-related diseases,” co-corresponding author Zhi-Kun Li of CAS said in the press release.
However, applying this technology to humans remains highly uncertain due to ethical and safety concerns. Current guidelines from the International Society for Stem Cell Research prohibit the reproduction of human stem cell-derived gametes because of potential risks.
As scientists continue to refine these techniques, the possibilities for future medical breakthroughs are vast—but so are the ethical considerations associated with them.
Kenna Hughes-Castleberry is the Science Communicator at JILA (a world-leading physics research institute) and a science writer at The Debrief. Follow and connect with her on BlueSky or contact her via email at kenna@thedebrief.org