Mouse with two dads survives to adulthood, major implications for same-sex human couples

In a breakthrough achievement, a team of researchers has successfully engineered a bi-paternal mouse – a mouse with two dads – that survived until adulthood. 

The experts targeted specific imprinting genes to overcome key barriers that previously prevented unisexual reproduction in mammals.

More specifically, by modifying a set of genes involved in reproduction, the experts successfully bypassed developmental roadblocks that had historically halted bi-paternal embryo growth before birth.

The research team was led by Wei Li, a professor of genetic engineering at the Chinese Academy of Sciences (CAS) in Beijing.

“This work will help to address a number of limitations in stem cell and regenerative medicine research,” noted Professor Li.

Genetic barriers to unisexual reproduction

Scientists have attempted to create bi-paternal mice before, but previous efforts failed at early developmental stages.

The biggest challenge was associated with imprinting genes, which regulate gene expression and play a crucial role in mammalian reproduction.

“The unique characteristics of imprinting genes have led scientists to believe that they are a fundamental barrier to unisexual reproduction in mammals,” explained Qi Zhou of CAS, a corresponding author of the study. 

“Even when constructing bi-maternal or bi-paternal embryos artificially, they fail to develop properly and stall at some point during development due to these genes.”

Creating a mammal with two dads

Earlier approaches involved generating oocytes (egg cells) from male pluripotent stem cells using ovarian organoids. These artificially derived oocytes were then fertilized with sperm from another male. 

However, when homologous chromosomes – which separate during meiosis to form sperm and egg cells – came from the same sex, imprinting abnormalities emerged. This led to severe developmental defects.

To overcome this, the researchers targeted 20 key imprinting genes using various gene-editing techniques, including frameshift mutations, gene deletions, and regulatory region modifications.

This genetic modification not only enabled the successful creation of bi-paternal mice, but also improved stem cell pluripotency, making them more stable.

Breakthrough in unisexual reproduction 

By precisely modifying imprinting genes, the team enhanced embryonic stem cell viability, allowing the bi-paternal mice to survive until birth – a feat that had never been achieved at this scale.

“These findings provide strong evidence that imprinting abnormalities are the main barrier to mammalian unisexual reproduction,” said study co-author Guan-Zheng Luo of Sun Yat-sen University in Guangzhou. 

“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.”

Many challenges remain

Despite this success, the study acknowledges several significant challenges. The birth rate was low, with only 11.8% of viable embryos developing to term. 

Health and lifespan concerns were evident, as many surviving mice exhibited growth abnormalities and shortened lifespans. 

Additionally, the bi-paternal mice that reached adulthood were sterile and unable to reproduce. However, they showed increased cloning efficiency, suggesting some unique biological properties.

Survival rates of bi-parental embryos

The researchers aim to further refine imprinting gene modifications to improve the survival rates of mice with two dads.

“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,” said study co-author Zhi-Kun Li of CAS.

Additionally, the team plans to expand these experiments to larger mammals, including monkeys, to investigate whether this genetic engineering approach could be applied beyond rodents. 

However, this transition presents a significant challenge, as imprinting gene combinations differ between species.

Implications for same-sex human couples

If scientists one day manage to safely and ethically adapt this kind of technology for human use, it could completely reshape how society views family.

The traditional definitions of parenthood might expand to include a broader range of family structures, reflecting a more inclusive understanding of what it means to be a family.

Of course, this possibility comes with a host of ethical and legal challenges. Society would need to have serious conversations about the long-term safety and health of children born through these methods.

In addition, laws would have to be written and revised around parental rights and consent for genetically engineered embryos.

Beyond the legalities, this breakthrough would likely spark a cultural shift. It could challenge long-held beliefs about reproduction and gender roles, leading us to reexamine our values around what constitutes a family.

Future of stem cell research

The study raises critical ethical and scientific questions about the future of unisexual reproduction in mammals. 

While these results demonstrate the possibility of bi-paternal reproduction, applying similar technologies to human reproduction remains highly restricted.

The International Society for Stem Cell Research (ISSCR) explicitly prohibits heritable genome editing for reproductive purposes, as well as the use of human stem cell-derived gametes for reproduction, citing safety concerns and ethical implications.

As the field of stem cell engineering and reproductive genetics advances, this research marks a major milestone in understanding genetic imprinting, developmental biology, and regenerative medicine. 

However, many hurdles – both biological and ethical – remain before such breakthroughs could have practical applications beyond the laboratory.

The study is published in the journal Cell Stem Cell.

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