Mice sharing two mothers’ DNA were healthy. Those born to two fathers only lived a few days.
Using stem cells and gene editing, researchers in China have created mice born to same-sex parents. Some of the mice had two biological mothers, with no paternal DNA. Others had two biological fathers, with no maternal DNA. Although the mice with two male parents only lived a few days, those with two mothers were healthy and went on to have children of their own.
The new technique uses a type of embryonic stem cell from one parent, and the natural egg or sperm of the other. Other attempts to facilitate same-sex reproduction have focused on creating sperm with a mother's DNA or eggs with a father's.
Gene editing helps bend the rules of reproduction in mammals
"I was impressed by this study because it is technically challenging," said Kenneth Ka-Ho Lee, a stem cell biologist at the Chinese University of Hong Kong who was not involved in the research.
It’s difficult to produce offspring from same-sex parents in mammals. That’s because during the development of sperm and eggs, certain genes from the mother and father shut off in a process called genetic imprinting. As a result, offspring typically need genes from both a mother and a father to be viable and develop properly.
To get around this and create mice with two female parents, the Chinese researchers used a type of embryonic stem cell that contains only one set of chromosomes. They deleted three regions of the genome associated with imprinting before injecting the edited stem cell from one female mouse into the egg of another. The process worked, resulting in 29 healthy baby mice—all female—from 210 embryos. The daughters lived to adulthood and went on to have healthy babies of their own the old-fashioned way.
“This new study shows that the major obstacle due to genomic imprinting can be overcome by extensive genetic manipulation in embryonic stem cells,” said Azim Surani at Cambridge University, who was not involved in the study. It was Surani who first discovered genomic imprinting in 1984.
A healthy adult mouse born to two mothers, shown with her own offspring. Credit: Leyun Wang
Mice with two fathers did not survive long
The Chinese team also attempted the process with male mice, but were less successful. “To produce the mice with two male parents, the process is more complicated,” explained Baoyang Hu, one of the study’s senior authors. With the male mice, the team had to remove seven imprinting regions of the genome from the stem cell. They then injected the cell along with another father’s sperm into an egg from which female genetic material had already been removed. The resulting embryos had only the fathers’ DNA and were carried to term by surrogate mothers. However, the mice with two fathers only survived a few days. The study’s authors say they plan investigate further to find ways to improve on this result.
Mouse pups born to two fathers, like the one shown here, only survived a few days. Credit: Leyun Wang
Mice have been born to same-sex parents in other labs
The new study isn’t the first time researchers have used stem cells to make mice with same-sex parents. Researchers have created mice with two mothers by deleting imprinting genes in the past. However, the mice born in those studies still had some developmental defects, say the authors of the new study.
In 2010, another study produced mice with two fathers using stem cells derived from skin. However, getting to a mouse with only male DNA with this technique required multiple generations.
Other scientists, including Surani, have also made progress with a different approach: making eggs and sperm from skin cells. This technique could also one day facilitate same-sex reproduction, using sperm containing a mother’s DNA or eggs containing a father’s.
No human experiments on the horizon
The technique used in the new study will not be helping human same-sex couples produce biological children anytime soon. “The comprehensive nature of the manipulations involved rules out—at least for now—any such attempts to generate bi-maternal human embryos,” said Surani.
Wei Li, a senior member of the Chinese team, said: “We can’t assert this technique will never be used in humans in the future. But for now, the answer is no. It is never too much to emphasize the risks and the importance of safety before any human experiment is involved.”
In fact, it’s not yet clear whether the same DNA deletions that successfully bypassed the genetic imprinting obstacle in mice would even work in primates. Li says the team now plans to test their approach in monkeys to find out.
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