How scientists bred mice with DNA from two same-sex parents

Scientists for the first time produced offspring with the genes of two male mice using the gene-editing technology known as CRISPR, but there's currently no indication that the same technique could be used to achieve same-sex reproduction among people, according to a study published Thursday in Cell Stem Cell, Andrew Joseph reports for STAT News.

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Background: Why mammals need the DNA of both parents

The research focuses on "genomic imprinting," an evolutionary feature that researchers believe prevents mammals from reproducing without both maternal and paternal genetic information, Joseph reports. In human genomes, there is a copy of the maternal gene and a copy of the paternal gene, and both are expressed in children. "But there are some 100 genes where 'imprints' stationed along the genome signal one copy to be active and one to be silent," according to Joseph.

These "silenced" genes are often fully functional, but are just 'turned off," Joseph writes. However, in mammals versus other animals, there are several crucial genes that are only functional in the maternal or paternal version of our DNA. For instance, with the gene IGF2, which is crucial for growth and development, only the paternal copy is normally active. If we only inherited maternal DNA, this gene would remain inactive and we wouldn't develop or grow properly.

In 2004, a team of Japanese researchers altered maternal genes to function as paternal genes in order to prevent genomic imprinting from blocking reproduction. The researchers bred 10 mice out of the more than 400 embryos they created, but only one of the 10 mice lived to adulthood.

Study details

For the latest study, researchers from the Chinese Academy of Sciences more extensively altered imprinting instructions using the DNA of two female mice and the DNA of two male mice.

The researchers grew embryonic stem cells, which were similar to egg and sperm cells because they contained half the chromosomes of other cells, but were different because they did not have genomic imprint instructions to silence particular paternal or maternal genes.

They were able to turn of these instructions using the DNA editor CRISPR. They also used the technology to delete imprinted regions found in embryonic stem cells for the paternal DNA and maternal DNA—which took their study a step further than the 2004 experiment. The researchers removed three imprinted regions from the embryonic cells for the maternal DNA and seven imprinted regions from the embryonic cells for the paternal DNA.

The researchers then simulated fertilization. For the bimaternal mice, the researchers injected the altered maternal sex cells into the sex cells from another female mouse to begin fertilization. For the bipaternal mice, they injected the altered paternal cells into the sex cells from another male mouse and then injected their combined sex cells into egg cells containing no DNA. The researchers then transferred the embryos created from the paternal DNA cells into female mice to form and carry the embryos to term.

Findings

In total, the researchers created 210 embryos and successfully bred 29 mice from the bimaternal DNA, Joseph reports. The researchers found the female mice born from the maternal DNA could reproduce with regular male mice. Specifically, they found the female mice bred 22 mouse pups from six litters. Of the pups, 13 of grew into adulthood, but nine died after birth.

From the bipaternal mice, the researchers successfully bred 12 from 477 embryos, but only two of the newborn mice lived longer than two days and none survived to adulthood. When the researchers measured the gene activity of the pups, they found some of their imprinted genes were not expressed as if they had been inherited from maternal DNA.

The researchers did not indicate whether they could replicate the experiment and find similar results in humans.

Comments

Researchers have said the study's findings are informative, because they provide new evidence showing imprinting prevents mammals from producing offspring without sexual reproduction, Joseph reports. The research also shows genome editing and cellular alternations are not sufficient to overcome imprinting and allow same-sex reproductive cells to reach normal levels of gene expression.

They noted there are technical, legal, and ethical challenges with moving forward with such research in humans. One concern is the unknown consequences. "If researchers created, say, a daughter from two mothers or two fathers, and if she were healthy and had children of her own, it is unknown what genetic ramifications might be passed onto the next generation," Joseph reports.

"[F]or now," Joseph writes, "the notion of reproducing the experiment in humans is more a matter of science fiction than science." However, he reports that researchers have said "the study sheds light on the underlying biology that foils mammals from spinning off offspring without sexual reproduction—unlike some reptiles, fish, and amphibians, which are capable of asexual reproduction" (Joseph, STAT News, 10/11).

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