Haploid Stem Cells Used To Produce Mice With Same Sex Parents

Mammals can only reproduce when parents of different sexes mate, even when artificial reproduction technology is used; core issue being genomic imprinting mechanisms which typically do not occur in most fish, reptiles, and amphibians. Obstacles that normally prevent same sex reproduction were revealed in this experiment, while indicating that some of them may be bypassed by using stem cells and targeted gene editing.

Genomic imprinting refers to suppression of genes from either mother or father during development of the cells that pass on genetic information during reproduction. This leads to absence of certain genetic regions in offspring not receiving genes from both parent sexes, which in turn this results in abnormally developed or unviable offspring among mammals.

Deleting imprinted genes from ova or eggs cells that have not reached maturity may be a way to overcome this mechanism. An early approach led to production of bimaternal mice in previous studies, however these pups showed genetic defects and the process was difficult to replicate.

Haploid embryonic stem cells were used in the current study successfully to produce healthy bimaternal pups. Cells are produced by one parent and contain half of the number of chromosomes and half the DNA present in the parent organism.

Stem cells from a female mouse underwent genetic editing to delete 3 imprinting regions which were then injected into cells from a second mouse. 129 embryos were generated by the procedure of which 29 survived and were born healthy and normally developed pups; which all survived to adulthood and produced their own progeny.

Bipaternal mouse pups were also produced using similar protocol to the bimaternal only more complex in this case 7 genetic imprint regions were deleted from the haploid ESCs and injected along with sperm from another male mouse into an egg cell from which the nucleus had been removed. Embryos were transferred with some placental material into surrogate mothers to carry until full term in the final steps, of which 12 live pups were born that died 48 hours after birth.

More improvement and refinement is required before this technology can become more common use as all of the imprinted genes have not been identified yet and there are ethical issues with creating vast numbers of unviable or severely defective offspring.

This research has shown what is possible, and that barriers can be eliminated in mammals through imprinting modification to create offspring from same sex parents, revealing some of the most important imprinted regions in the process that hinders development of mice with same sex parents which are interesting for studying genomic imprinting and animal cloning.

“Your scientists were so preoccupied with whether or not they could, they didn't stop to think if they should, and what is the need.” ~Dr. Ian Malcolm, Jurassic Park