Mice with two mums raise many questions

Chinese researchers have bred healthy mice with two mums and no dads. They’ve had less success with dads alone, however, and stress that there are still obstacles to using these methods in other mammals.

Among the greatest obstacles is probably the fact that their methods involve stem cells and targeted gene editing.

The team from the Chinese Academy of Sciences, Beijing, set out to examine what makes it so challenging for animals of the same sex to produce. Their paper was published in the journal Cell Stem Cell.

“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,” says co-senior author Qi Zhou.

Embryonic stem cells (ESCs) can turn into any cell in the body and have the potential to be used in preventing or treating disease in humans. Haploid ESCs contain only a single set of chromosomes, rather than the usual one from each parent.

To produce bi-maternal mice, Zhou and colleagues deleted three imprinting regions of the genome from haploid ESCs containing a female parent’s DNA and injected them into eggs from another female. They produced 29 live mice from 210 embryos. All lived to adulthood and produced their own offspring.

The process with male parents only was more complex, involving injecting sperm as well as ESCs into an egg cell and transferring embryos and placental material to surrogate mothers.

Twelve pups were born, but only survived for a couple of days. The researchers are confident, however, that with further work they can produce two-father offspring that survive to adulthood

Some reptiles, amphibians and fish can reproduce with parents of the same sex but it’s challenging for mammals, even with the help of fertilisation technology, 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 the imprinted genes from immature eggs, researchers have produced bi-maternal mice in the past, but the methods were impractical, and the newborn mice still showed defective features, the researchers say.

“This research shows us what’s possible,” adds Zhou’s colleague, Zhi-Kun Li. “We saw that the defects in bi-maternal mice can be eliminated and that bi-paternal 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.”

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 and concerns for the offspring that don’t survive or that experience severe abnormalities.

Not surprisingly, the new paper has created significant interest. In Australia, the Deputy Director of the Centre for Stem Cell Systems at the University of Melbourne, Megan Munsie, is among those to raise technical and ethical issues.

“While this finding provides insights into the control of reproduction, being able to routinely make mice and other mammals from same-sex parents will remain a significant challenge,” she says.

“At a technical level, significant refinements will need to be made to avoid growth abnormalities and other complications. It is likely that a different combination of genes will need to be manipulated to allow normal development for each species, with a high cost to pay if the ‘wrong’ genes are manipulated.”

Munsie says the paper is also a timely reminder both of the power of technology and of the need to discuss its potential impact on society, even when at such a preliminary stage.

“We need to pause and evaluate under what circumstances, if any, the technology should be applied and, if so, to whom,” she says. “Simple headlines about being able to create young from same sex parents fails to fully capture the complexity and challenges ahead.”