It is now possible to engineer healthy mice with two mothers and no father, according to a new study in Cell Stem Cell. Using stem cells and targeted gene editing, researchers also succeeded in creating mice with two fathers and no mother, but theses pups did not survive to adulthood. This is not the first time researchers have produced mice with same-sex parents, and the findings in no way indicate that this practice would be possible in humans. But the results do shed new light on reproduction in mammals.
“We tried to find out whether more normal mice with two female parents, or even mice with two male parents, could be produced,” said coauthor on the study Qi Zhou of the Chinese Academy of Scientists, in a statement. “We were interested in the question of why mammals can only undergo sexual reproduction.”
It may seem like a silly question, but there’s good reason to wonder why mammals can only reproduce when a male fertilizes an egg produced by a female. Parthenogenesis, a form of asexual reproduction in which embryos develop without fertilization, exists naturally among reptiles, amphibians, and fish. In mammals, however, there is the problem of genomic imprinting. For most genes, mammals inherit two working copies from the father and mother but, for a handful of crucial genes, only one working copy makes it through the reproductive crucible. The other copy is shut off (usually by the addition of methyl groups—carbon and hydrogen molecules that silence genes epigenetically). The upshot is that a mouse pup with two mothers or two fathers would either not develop at all, develop abnormally, or prove non-viable.
In theory, turning those silenced genes back on should produce healthy mammals from same-sex parents. Indeed, Japanese researchers pulled this off in 2004 with Kaguya, the first mouse to be born from two mothers. “However, the generated mice still showed defective features, and the method itself is very impractical and hard to use,” Zhou says.
For this new study, Zhou and colleagues used gene editing technology to delete three of those troublesome imprinting regions from a specific type of embryonic stem cell, which contains the DNA from only one, female, parent. They then injected these stem cells into eggs from another female mouse. This produced 29 live mice from 210 embryos (by contrast, Kaguya was one of two successes—out of 457 attempts). The mice developed normally, and lived to reproduce. Zhou and his team also engineered 12 mice with two genetic fathers. Here, they injected modified male stem cells into an egg that was missing all of its female genetic material, and then implanted the “male egg” into a surrogate female. These pups, however, only survived 48 hours.
Zhou makes no claims that his work could translate into human applications and, indeed, a preliminary mouse study is nothing to get overly excited about. But he hopes that it will lay the groundwork for future studies of genomic imprinting, and encourage other researcher to push the boundaries of targeted gene editing. “The research shows us what’s possible,” he says.