AsianScientist (Oct. 19, 2018) – Researchers at the Chinese Academy of Sciences (CAS), China, were able to produce healthy mice with two mothers that went on to have normal offspring of their own. Mice from two dads were also born but only survived for two days. They presented their findings in Cell Stem Cell.
While some reptiles, amphibians and fish can reproduce with one parent of the same sex, it is challenging for mammals to do the same even with the help of fertilization technology. In mammals, certain maternal or paternal genes are shut off during germline development by a mechanism called genomic imprinting. Therefore, offspring of two mothers or two fathers might experience developmental abnormalities, or might not be viable.
In the present study, researchers led by Professors Zhou Qi, Hu Baoyang and Li Wei of CAS created mice from same-sex parents by using haploid embryonic stem cells (ESCs) which contain half the normal number of chromosomes and DNA from only one parent.
The researchers created the mice with two mothers by deleting three imprinting regions of the genome from haploid ESCs containing a female parent’s DNA, followed by injecting those ESCs into eggs from another female mouse. The researchers produced 29 live mice from 210 embryos. The mice were normal, lived to adulthood and had babies of their own.
“We were interested in the question of why mammals can only undergo sexual reproduction. 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 with gene deletions,” said Zhou.
One advantage of using haploid ESCs is that even before the problematic genes are knocked out, they contain less of the imprinting programming that ultimately causes maternal- or paternal-specific genes to be expressed.
“We found in this study that haploid ESCs were more similar to primordial germ cells, the precursors of eggs and sperm. The genomic imprinting that’s found in gametes was ‘erased,’” said Hu.
Twelve live, full-term mice with two genetic fathers were produced using a similar but more complicated procedure. Haploid ESCs containing only a male parent’s DNA were modified to delete seven key imprinted regions. The edited haploid ESCs were then injected—along with sperm from another male mouse—into an egg cell that had its female genetic material removed. This created an embryo containing only genomic DNA from the two male parents. These embryos were transferred along with placental material to surrogate mothers, who carried them to term.
These pups survived 48 hours after birth, but the researchers are planning to improve the process so that the bipaternal mice live to adulthood. Li notes that there are still obstacles to using these methods in other mammals, including the need to identify problematic imprinted genes that are unique to each species. Concerns surrounding offspring that do not survive or experience severe abnormalities must also be addressed.
“This research shows us what’s possible,” said Li. “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 article can be found at: Li et al. (2018) Generation of Bimaternal and Bipaternal Mice from Hypomethylated Haploid ESCs with Imprinting Region Deletions.
Source: Cell Press; Photo: Wang Leyun.
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