Single-sex mouse parents

Currently, the only way for a single-sex couple to have a child that is genetically related to them, is to use IVF to combine donor sperm/egg cells with DNA from one of the two parents in the couple. However, a recent study published in Cell Stem Cell was able to produce healthy offspring from the DNA of two female mice with no male DNA. The research suggests that in the future, it might be possible for single-sex couples to have a child that is genetically related to both of them without the need for a surrogate/donor.

Our basic understanding of mammalian sexual reproduction is that it requires both male DNA from a sperm cell and female DNA from an egg cell to combine to form an embryo that carries both genomes. We also know that every gene in our DNA is represented by two copies (alleles) of that gene. Normally, the expression of a single gene is determined by a combination of both of these alleles. However, a process called genomic imprinting selectively switches off about 1 per cent of either our maternal or paternal alleles. This means that the expression of some genes is solely determined by the remaining ‘on’ maternal/paternal allele. For example, the expression of the insulin-like growth factor gene is entirely dependent on the paternal allele because the same gene in the maternal DNA is shut off.

We know that these imprinted regions of DNA are incredibly important for normal embryonic development because in previous experiments, embryos that didn’t receive genetic material from both sexes experienced severe developmental abnormalities and often died before birth.

However, a new study carried out in China by Zhou et al showed that it is possible to produce healthy offspring with DNA from two females. They generated embryonic stem cells containing DNA from one female and then modified three regions of imprinted DNA, essentially erasing the genomic imprinting in these cells (so no genes were shut off). The modified embryonic stem cells were then injected into a normal egg cell of another female mouse so the resulting offspring had a combination of DNA from the two females. From the 210 embryos that were created, 29 mice were born that lived to adulthood and had offspring of their own when mated with males. It may be that since none of the genes in the embryonic stem cells were shut off,  they were able to complement the genes that were shut off in the egg cell – giving the embryos the full complement of genes required for normal development.

Researchers also tried to produce offspring with DNA from two males, but although live offspring were born, none survived. This difference may be because female embryonic stem cells contain fewer regions of imprinted genes so less modification of the DNA is required.

This study suggests that by using a combination of stem cells and gene editing technology it might be possible to overcome the challenges facing single-sex reproduction, making it possible for both partners in a single-sex couple to contribute genetic material to their child. However, it should be noted that the problematic regions of imprinted genes are not the same in all species and we have yet to identify the imprinted genes that are present in the human genome. We should also keep in mind that the current success rate of this procedure in female mice is about 13 per cent, so there is a long way to go before this procedure can be safely translated into humans.

Image: artyangel via Pixabay

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