May 30, 2024

Will the male of the species go the way of the dodo?

Chinese researchers create healthy mice from same-sex mothers

Are men becoming obsolete? This dire news (or possibly good news in some circles) has been voiced many times as stem cell research unfolded over the past 20 years. Now there is an experiment to give it some credibility.

From two mothers, Chinese researchers have bred healthy mice which went on to have normal pups of their own. They achieved this feat by altering stem cells from a female mouse and injecting them into the eggs of another. Of 210 embryos, 29 survived.

Mice pups from two fathers were also born using a similar but more complex approach, but these only survived for a couple of days.

The research was published in Cell Stem Cell by researchers from the Chinese Academy of Sciences.

While some reptiles, amphibians, and fish can reproduce with one parent of the same sex, it is challenging for mammals with the help of fertilization technology. In mammals, because certain maternal or paternal genes are shut off during germline development by a mechanism called genomic imprinting, offspring that don't receive genetic material from both a mother and a father might experience developmental abnormalities or might not be viable. By deleting these imprinted genes from immature eggs, researchers have produced bimaternal mice–mice with two mothers–in the past. “However, the generated mice still showed defective features, and the method itself is very impractical and hard to use,” says co-senior author Qi Zhou.

To produce their healthy bimaternal mice, the researchers 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 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,'” says 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 nucleus, and therefore 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.

“This research shows us what's possible,” he 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.”

Australian IVF expert Robert Norman commented, “The concept is intriguing for human reproduction, particularly for same-sex couples but there are far too many uncertainties at present to attempt such an approach for many years to come.

“The first challenge will be to make babies from artificially derived eggs and sperm from male and female couples, an exercise that is increasingly important for infertile men and women who have no functioning gametes of their own. No ethical permission has been given anywhere to attempt to produce live offspring although embryos have been produced experimentally with no transfer to the uterus.”

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