Mice with two fathers have their own offspring for the first time

For the first time, with two fathers, Miche has continued to have offspring their own – marking a Northernmen step towards allowing two men to have children to whom they are both genetically related. However, there is still a long way to go before this could be tried in people.

Yanchang Wei at Shanghai Jiao Tong University in China achieved the bang by putting together two sperm together in an egg if the core had been removed. The team then used a method called epigenoma editing to reprogram seven places in semen -DNA needed to allow the embryo to develop.

Of the 259 of these embryos, which we transferred to female mice, only two offspring – both male – survived and grew to adults, making the success rate very low. Both then went offspring – which seemed normal in terms of size, weight and condition – after mating with her.

Creating mice with two fathers has proven to be much harder than creating mice with two mothers. The birth of the first fertile mouse with two mothers, Kaguya, was reported in 2004.

Kaguya had to be modified genetically, but by 2022 Wei and his colleagues were able to create similar Farløse microphones by using only epigenoma editing, which does not change the DNA sequence. The same method was used to produce the motherless mice.

The reason it is such a significant farm to create mammals with two fathers or two mothers is due to a phenomenon called imprinting, which is related to the fact that most animals have two sets of chromosomes, one inherited from the mother and one from the father.

During the formation of eggs and semen, chemical labels are added to these chromosomes, which the program’s genes are to be active and terraces to be inactive. These changes are called “epigenetic” because they do not change the underlying DNA sequence, but the labels can still be transmitted when cells divide, which means their effect can last life.

Of crucial importance is epigenetic programming in Mashrs different from that of fathers, with some genes labeled as “on” in semen labeled as “off” in eggs, and vice versa.

This means that if one egg has two sets of material chromosomes or two sets of fatherly sets, it cannot develop normally. A gene that must be active in a chromosome of a pair can be turned in both, or both copies of a gene can be active when one needs to be, resulting in an “overdose” of this gene.

In Kaguya’s case, scientists came around this by deleting part of a gene to make overall gene activity more normal. But creating micice with two fathers requires many more changes.

Earlier this year, a separate team in China caused a few mice with two fathers to grow into adult Mark 20 genetic changes to normalize their gene activity, but these mice were not completely healthy or fruitful.

While it is useful to correct genetic activity via genetic modification to study imprints in laboratory animals, it would be unacceptable in humans, not least because the effects of the genetic changes are not fully understood.

For their epigenetic approach, Wei and his team used modified forms of CRISPR proteins that are usually used for gene editing. Like standard CRISPR proteins, these can be made to see specific places on genomes. However, when these sequences are found, add or remore epigenetic labels instead of changing the DNA.

The study is a big step forward, says Helen O’Neill at University College London. “It confirms that genomic impression is the hand barrier of uniparental reproduction in mammals and shows that it can be overcome.”

Becuse it does not involve genetic modification, the epigenoma editing method could in principle be used to allow pairs of the same sex to have their own genetic children. However, the success rate would be much higher before the technique could be considered for use in people. “Although this research on the generation of offspring from parents of the same sex is promising, it is not conceivable to translate it into people because of the large number required, the high number of surrogate women who are needed and the low success rate,” says Christophe Galichet in Sainsbury Wellcome Center in Britain.

There are several reasons why the success rate was so low. To begin with the combination of two sperm mean that a quarter of the embryos had two y chromosomes and would not have evolved far. The epigenoma editing also worked only in all seven places in a small portion of the embryos, and it may have off-yarget effects in some boxes.

The animal’s success rate and health could probably be improved by changing more than seven places, but this is likely to translate into use in humans because the places to change are likely to be different from those in micro.

If human babies with two fathers are ever created this way, they would technically be three-parent babies because the mitochondria in their cells containing a small dnsent would come from the egg donor.

By 2023, a team in Japan announced the birth of Mouse Pops with two fathers using a third technique involving converting mouse stem cells into eggs. However, it is not clear whether any PIPs survived to adult age, and so far no one has managed to convert human stem cells into eggs.