Embryonic stem cells with specific genes deleted have been used to produce mice with the DNA of two parents of the same sex. Those with two mothers, and therefore no male genetic parentage, were apparently healthy and produced offspring of their own. Unfortunately, the mice with two genetic fathers were less successful died within days of birth.
The birds and bees story we tell children is quite an oversimplification when it comes to the animal kingdom as a whole. Many invertebrates reproduce asexually, at least intermittently, including in species where this was quite unexpected. Some reptiles no longer determine sex through chromosomes, sometimes with fascinatingly complex results. Mammals, however, stick to the male-female parentage script.
"We were interested in the question of why mammals can only undergo sexual reproduction,” said Professor Qi Zhou of the Chinese Academy of Sciences in a statement. A process known as genetic imprinting can shut down some maternal or paternal genes during mammalian development. Consequently, offspring that don't get genetic material from both are likely to have developmental abnormalities, or not be born alive at all.
Mice with two mothers have been produced previously by deleting imprinting genes. Despite some successes, however, mice produced that way did not consistently develop normally, and Zhou considers the previous method “very impractical and hard to use.”
In Cell Stem Cell Zhou describes starting off with haploid embryonic stem cells, which contain only one version of each chromosome, inherited from a female parent. These cells are already used for genetic studies, and have been produced in humans, as well as a variety of mammals. Zhou and co-authors then deleted the regions of the genome responsible for imprinting and injected the cells into eggs from a different mouse.
From 210 embryos produced in this way, the team produced 29 live mice. The resulting mice were healthy, although somewhat smaller than mice conceived through natural means, and developed to adulthood where they mated normally, and the majority of their offspring were healthy.
The authors describe the process as being simpler than those used previously, as well as more effective, because the haploid cells resemble primordial germ cells, which go on to become eggs and sperm.
Attempts to achieve something similar with two fathers were less successful. Haploid stem cells and sperm alone can't produce an embryo, so the two were implanted into an egg whose nucleus, containing the mother's DNA, had been removed. Embryos with two genetic fathers produced in this way survived to term in surrogate mothers, and had bigger bodies, with larger internal organs, than other mice.
The paper attributes this to a previously identified phenomenon, known as conflict theory, where genomes from fathers fight the mother's body to obtain more resources. These extra resources did them no good, however; the offspring only survived for just a few days after birth, similar to the outcome using a different method in 2011.
Adapting the technology to other species will be challenging because the imprinted genes that need to be deleted vary. Social conservatives will no doubt be appalled at the idea of children with biological parents of the same sex, but it is more likely to be the high risk of developmental abnormalities that will prevent implementation of something similar in humans any time soon. Nevertheless, as senior author Dr Wei Li said: “This research shows us what is possible.”
