Naturally, mammals can only reproduce sexually – which has its upsides of course, but it makes us a little less adaptable than other species that can do things by themselves. In investigating why that's the case, Chinese researchers have successfully managed to breed healthy mice with genetic material from two mothers, using stem cells and gene editing.
Some animals effectively have a choice: they can reproduce sexually if there are partners nearby to mix-n-match genetics, or if they're on their own, they can go solo to keep the species going. This ability has been observed in many species, such as sharks, termites, worms, crayfish, cockroaches and salamanders. But mammals don't have that luxury.
"We were interested in the question of why mammals can only undergo sexual reproduction," says Qi Zhou, co-senior author of the study. "We have made several findings in the past by combining reproduction and regeneration, so we tried to find out whether more normal mice with two female parents, or even mice with two male parents, could be produced using haploid embryonic stem cells (ESCs) with gene deletions."
This technique was chosen to help overcome a problem particular to mammals. During development, certain genes are "stamped" with information from one parent or the other. This process, known as genomic imprinting, means that if paternal or maternal genes are missing the embryo might not develop properly. Past research has managed to breed mice with material from two mothers (known as bimaternal) by deleting these imprinted genes from immature eggs, but the offspring still suffered from development problems.
The key to success in the new study, say the researchers, were the haploid embryonic stem cells. First, the team deleted three imprinting regions of the genome from haploid ESCs from one female parent, then injected them into eggs from another mother. From 210 embryos, 29 live baby mice were born. Those bimaternal babies grew up to be healthy adults, and in turn had their own kids.
The team also tried a similar experiment with two fathers, but the process is more complicated. First, seven key imprinted genes were deleted from haploid ESCs of one male parent, and then these were injected into an egg cell along with sperm from another male mouse. Importantly, the egg cell's nucleus, which contains the female genetic material, had already been removed.
As a result, these embryos had only DNA from the two fathers, and were carried to term in surrogate mothers. Unfortunately, the 12 offspring produced through this method were less successful than those with two mothers, and none of them survived more than 48 hours.
This technology still has a lot of kinks to iron out, so there's a long way to go before it could be considered for use in humans. Still, if it does it could open the door for same-sex couples to have their own genetic children. It seems a little less complicated (technically and ethically) than an earlier study that involved growing female mice from one father's stem cells then mating them with another male, so that the next generation had only DNA from the two fathers.
"This research shows us what's possible," says Baoyang Hu, co-senior author of the study. "We saw that the defects in bimaternal mice can be eliminated and that bipaternal reproduction barriers in mammals can also be crossed through imprinting modification. We also revealed some of the most important imprinted regions that hinder the development of mice with same sex parents, which are also interesting for studying genomic imprinting and animal cloning."
The research was published in the journal Cell Stem Cell.