In a groundbreaking scientific first, a mouse with two male parents has successfully reached adulthood.
Researchers achieved this milestone using embryonic stem cell engineering, precisely modifying key genes involved in reproduction to create the bi-paternal mouse.
This breakthrough method enabled scientists to overcome barriers previously thought insurmountable in unisexual mammalian reproduction.
In past experiments, mouse embryos stopped developing early because using two male mice caused genetic issues during fertilisation, leading to severe birth defects.
However, the researchers behind the new study suspected that these genetic issues were caused by 'imprinting' genes – these are genes that typically must be inherited from both a male and a female parent.
“The unique characteristics of imprinting genes have led scientists to believe that they are a fundamental barrier to unisexual reproduction in mammals,” said Prof Qi Zhou, co-corresponding author of the study.
“Even when constructing bi-maternal or bi-paternal embryos artificially, they fail to develop properly, and they stall at some point during development due to these genes.”
From this theory, the researchers modified 20 key imprinting genes using various techniques before implanting the altered embryos into surrogate mothers.
Their findings revealed that these genetic edits not only enabled the creation of bi-paternal mice but also, in some cases, allowed them to survive to adulthood.
“These findings provide strong evidence that imprinting abnormalities are the main barrier to mammalian unisexual reproduction,” says co-corresponding author Prof Guan-Zheng Luo of Sun Yat-sen University.
“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.”
But it's not all good news. The researchers reported that only 11.8 per cent of viable embryos developed to birth, and even then, some did not survive to adulthood due to developmental defects.
In fact, most of the mice that reached adulthood had abnormal growth and shorter lifespans, and those that survived were also sterile.
The team is working to fix these problems by studying how changing certain genes could help embryos develop better. They also plan to test their research on larger animals, like monkeys. Until then, it's very unclear whether this technology will be used for humans.
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