Scientists create fertile mice with two fathers for first time

Times

5 days ago

Scientists have created fertile mice from male genetic material alone, a breakthrough that could one day open the door to human babies who inherit their genes from two fathers.
The experiment, led by Professor Yanchang Wei at Shanghai Jiao Tong University in China, marks a milestone in the quest to overcome the biological barriers to same-sex reproduction.
The research, published in the journal PNAS, involved inserting DNA from two sperm cells into an egg that had been emptied of its nucleus. This resulted in an androgenetic embryo — one that contains only male genetic material — which was then implanted into the uterus of a surrogate mother mouse.
In mammals androgenetic embryos typically fail early in development due to a phenomenon known as genomic imprinting. Roughly speaking, this refers to how certain genes are turned on or off depending on whether they came from the mother or father, via chemical modifications or 'epigenetic tags' that are attached to their DNA.
Wei and his colleagues overcame this by using an editing technique to 'reprogramme' seven regions of the DNA of one of the sperm cells placed inside the egg. Epigenetic tags were altered to restore the genetic balance normally achieved by having input from a male and a female.
Out of 259 embryos implanted into female mice, only two male pups survived to adulthood. Though the success rate was low, both males went on to have healthy offspring with female partners — the first time this has been achieved with two-father animals.
The science is still in its early stages and there is no prospect of human babies being born with two fathers in the near future. However, the implications may be profound.
• 'Motherless' mice created from embryos with only male genes
Unlike some previous attempts to produce same-sex mammalian offspring, the technique used involved editing only the epigenetic features that control the activity levels of genes, rather than the genes themselves. This may makes it more useful for future clinical applications.
However, the extremely low success rate of the technique used in the study would require an unacceptable number of eggs and surrogate mothers. One reason for the low success rate is that combining two sperm increases the odds of producing embryos with two Y chromosomes, which cannot develop. The epigenetic reprogramming also only worked fully in a fraction of the embryos.
In 2004, Japanese researchers created a female mouse from two mothers — a breakthrough at the time. But producing viable offspring from two sperm has proven far more complicated, requiring a deeper understanding of imprinting.
If the technique were ever adapted for use in humans, such children would technically still have a 'third parent' in the egg donor, whose mitochondrial DNA would remain in the embryo. However, they would inherit their nuclear DNA, which contains the vast majority of their genetic code, from two men.