Mice whose genetic parents are both male have survived to adulthood for the first time. However, achieving this required extensive genetic modification, among other things, that could never be attempted in people.
These aren鈥檛 the first mammals with same-sex parents 鈥� mice with two mothers were first created in 2004, and while unusually small, they appeared to live even longer than normal. But creating mice with two fathers has proved more difficult.
Nonetheless, in 2018, a team led by i at the Chinese Academy of Sciences in Beijing reported the birth of 12 mice with two fathers, although they weren鈥檛 healthy and none survived to adulthood. Now, the same team聽has managed to create such mice that did survive into adulthood, but they didn鈥檛 live as long as normal and can鈥檛 have offspring of their own.
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These researchers might not be the only ones to achieve this. In 2023, a team in Japan announced the birth of seven apparently healthy mice with two fathers, but we don鈥檛 know if these survived until adulthood.
So why it is so difficult to create mammals with two fathers? And could we one day do this in humans, so two men could have children that are a genetic mix of both of them?
The answer to the first question is a phenomenon called imprinting. The DNA in cells contains recipes, or genes, for making key molecules. But you don鈥檛 want, say, muscle proteins being made in a brain cell, so as cells develop into specialised types, unneeded genes get switched off, or silenced.
One way cells do this is to add chemical labels to DNA. If you think of the genome as a recipe book, these labels are like sticky notes saying: 鈥淒on鈥檛 make this recipe.鈥� They can be added and removed in a so-called epigenetic change, in other words without altering the underlying DNA.
This process also occurs in sperm and egg. However, crucially, the genes that get silenced in sperm are different to those silenced in eggs, and the distinct pattern of genomic activation/deactivation in these cells is what we call imprinting. So if you simply put the DNA from two males 鈥� or two females 鈥� together in an embryo, it won鈥檛 develop normally because some genes that should be active are silenced and vice versa.
Why does imprinting happen? It is thought to be a result of an evolutionary battle between the sexes. Males turn off genes that limit the growth of their offspring, but offspring that grow too large before birth can harm females, so females turn off genes that boost fetal growth at their expense.
To create animals with same-sex parents, the male/female imprinting patterns have to be recreated. Mimicking the female pattern requires more changes than mimicking the male pattern, so it is harder to create mammals with two fathers than two mothers.
at Kyushu University in Japan achieved this by finding male cells that had naturally lost the Y chromosome and generating eggs from them 鈥� thus resetting the imprinting pattern to that in eggs 鈥� and then fertilising them with sperm.
Hayashi revealed the birth of seven apparently healthy mice in 2023. 快猫短视频 has asked him if any survived to adulthood, but had not received a reply at the time of writing.
Li has instead been genetically modifying mice to disable genes that are normally imprinted 鈥� the equivalent of tearing pages out of the recipe book rather than adding sticky notes.
To get two-father, or bipaternal, mice to survive to adulthood, his team had to disable 20 genes 鈥� compared with three for mice with two mothers 鈥� and even this isn鈥檛 enough.
鈥淚t is fair to say that these mice were not completely healthy,鈥� says Li. 鈥淚t is likely that additional imprinted genes, beyond the 20 we targeted, could contribute to improving the health of these mice.鈥�
Generating the mice also involved making embryos from eggs and collecting embryonic stem cells from them on multiple occasions.
鈥淎t present, it is unthinkable to translate [Li鈥檚] method of generating bipaternal animals from mice to humans,鈥� says at the Sainsbury Wellcome Centre in the UK. But the results are still valuable, he says.
For one thing, they support the idea that imprinting is the result of a battle between the sexes. Li鈥檚 team found that the bipaternal mice grew especially fast and had abnormalities related to organs growing too big.
But if the aim is to allow two men to have genetic children of their own, with the help of a surrogate mother, Hayashi鈥檚 approach is more promising, as it can be done without genetic modification. However, key steps in his process can鈥檛 yet be done in people, so we are still a very, very long way from creating children with two genetic fathers.
Cell Stem Cell
