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Researchers at the Chinese Academy of Sciences were able to produce healthy mice with two mothers that went on to have normal offspring of their own. Mice from two fathers were also born but only survived for a couple of days.
Researchers examined what makes it difficult for animals of the same sex to produce offspring and suggests that some of these barriers can be overcome using stem cells and targeted gene editing.
Some reptiles, amphibians, and fish can reproduce with one parent of the same sex, it’s different for mammals to do the same with fertilization technology. In mammals, because certain maternal or paternal genes are shut off during germline development by genomic imprinting, offspring that don’t receive genetic material from a mother and a father might experience developmental abnormalities or might not be viable.
By deleting imprinted genes from immature eggs, researchers produced bimaternal mice- mice with two mothers in the past. However, the generated mice still showed defective features, and the method is very impractical and hard to use.
To produce their healthy bimaternal mice, Zhou, co-senior author Baoyang Hu, co-senior author Wei Li, and their colleagues used haploid embryonic stem cells (ESCs), which contain half the normal number of chromosomes and DNA from only one parent and which the researchers believe were the key to their success.
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 and injected them into eggs from another female mouse. They produced 29 live mice from 210 embryos. The mice were normal, lived to adulthood, and had babies of their own.
One advantage of using haploid ESCs is that 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.
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. 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 nucleus, and therefore its female genetic material, removed. This created an embryo containing only genomic DNA from the two male parents.
The 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.
Similar results were achieved in 2011 but using a method that relied on a female intermediary produced from the first father’s stem cells to mate with the second father. That method sidestepped the problem of genomic imprinting but presents ethical and practical hurdles if this technology were to ever be considered for humans.
Defects in bimaternal mice can be eliminated and that bipaternal reproduction barriers in mammals can also be crossed through imprinting modification. Important imprinted regions that hinder the development of mice with same sex parents are also interesting for studying genomic imprinting and animal cloning.