Research published in Cell Stem Cell demonstrates genome editing has enabled mouse pups to be born from same-sex parents.
Dr Dusko Ilic, Reader in Stem Cell Science, King’s College London Faculty of Life Sciences and Medicine, said:
“In this cutting-edge study, the Chinese scientists edited the genome of haploid mouse embryonic stem cells (mESC) by deleting multiple imprinted regions and using donor eggs to create offspring that genetically match the same-sex parents.
“In the case of bimaternal offspring, they injected genome-edited female haploid mESC into a mouse donor egg with intact haploid set of chromosomes. The offspring were healthy and fertile.
“In the case of bipaternal offspring, they injected genome-edited male haploid mESC and a spermatozoid into an enucleated egg to generate diploid mESC originating from two males. Such mESC were then injected into tetraploid blastocyst, which would provide only extraembryonic tissue, to create bipaternal offspring. All of them dies 48 hours post birth with multiple abnormalities.
“The study is shedding light on various aspects of mammalian reproduction and development and it is opening new avenues for future research. To consider exploring similar technology for human application in the near future is implausible. The risks of severe abnormalities is too high, and it would take years of research in various animal models to fully understand how this could be done safely.”
Prof. Azim Surani, Director of Germline and Epigenomics Research, The Gurdon Institute, University of Cambridge, said:
“Each parent in mice and men contribute an equal number of chromosomes at fertilisation. In humans, fathers and mothers contribute 23 chromosomes each to the embryo. The study on mice confirms that it is not sufficient to have the right number of chromosomes (46 in humans), even though fathers and mothers make a similar genetic contribution to the embryo. Evidence shows that parental chromosomes however also carry a unique epigenetic memory of their parental origin, and this epigenetic information is essential for healthy development. This epigenetic memory referred to as “genomic imprinting” constitutes a major barrier to the development of embryos that contain chromosomes from two women (bi-maternal) or two men (bi-paternal). The chromosomes contributed by mothers and fathers to the embryo contain reciprocal epigenetic information making it essential that chromosomes from both parents are present at the start of development. This new study shows that the major obstacle due to genomic imprinting can be overcome by extensive genetic manipulation in embryonic stem cells to create embryos with chromosomes from two females (‘bi-maternal”). The comprehensive nature of the manipulations involved rules out (at least for now), any such attempts to generate bi-maternal human embryos. The bi-paternal embryos in this experiment, in any case, did not survive for long”.
Dr Christophe Galichet, Senior Laboratory Research Scientist, The Francis Crick Institute, said:
“While same-sex parent reproduction is possible in some lower vertebrates (some fish or reptiles), there are no known cases of same-sex parent reproduction in mammals (including Human). In mammals, sperm needs to meet the egg for the generation of offspring.
“In the paper from Li et al. published in Cell Stem Cell, the authors overcame the same-sex parent reproduction barrier in mice. They could generate some mice from two mums (Bimaternal mice) or two dads (Bipaternal mice). The paper is explaining the barriers that need to be broken in order for same-sex parent reproduction to happen.
“The sperm from dad and the egg from mum, each brings genetic information within their chromosomes; one half from dad and one half from mum. When the two meet, the information is combined to generate a unique offspring. However, some parts of mum and dad chromosome are imprinted meaning that genetic information will be given only from mum’s chromosome (maternal imprinting) or dad’s chromosome (paternal imprinting).
The authors have used a specials embryonic stem cells (ESCs) in which only half of the chromosome are present (haploid ESCs) hence resembling the chromosomal content of a sperm or an egg. Normally ESCs would already have imprinting information, however, the authors have looked at the imprinting information of the haploid ESCs and found, with time, an erasure of the imprinted information comparable to that of germ cells (cells which will then become sperm or egg).
“Previous studies have shown that bimaternal reproduction of mice was possible by removing two maternal imprinted regions. Mice were born but were growth retarded. To better understand the phenomenon, the authors have found that a third region needed to be removed for normal growth of mice of bimaternal origin. In both cases, one female modified haploid ESCs were injected into an egg resulting in live birth.
“For bipaternal reproduction, the authors first removed six imprinted regions that have shown to have some parent-of-origin effect on embryonic lethality. However, to produce offspring of bipaternal origin, the authors had to inject an empty egg with one modified haploid ESCs and a sperm, let the embryo develop until ESCs can be derived. The bipaternal ESCs were then injected into tetrapoid embryos (embryos that can use only the donor ESCs for the development of the foetus). The bipaternal offspring showed overgrowth at birth. The authors found that another imprinted regions needed to be removed and, using similar method, generated seven-deleted-imprinted-region haploid ESCs. The bipaternal offspring that were born appeared normal in size.
“The authors have made an extremely important step forward in understanding why mammals can only reproduced sexually. In mammals, some genetic information must be given by mum or dad chromosome in order to generate an offspring. While human haploid embryonic stem cells, cells in which only half of the chromosome are present, have been generated, it is unthinkable to generate human baby that way. Indeed, few regions would have to be deleted in order for the embryo to develop hence generating genetically modified embryos. Furthermore, it is not known if the imprinted regions that were deleted in mice are the same in human. If one were to undertake to generate “lesbian” or “gay” baby that way, it would take a huge amount of time only for the generation of the modified ESCs, with very little success at the end (ie 2.5% for bipaternal reproduction in mice which might be even lower in human).”
“Generation of uniparental mice from hypomethylated haploid ESCs with imprinting region deletions” by Li et al. was published in Cell Stem Cell at 16:00 UK time on Thursday 11th October.
All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/tag/genome-editing/
The SMC also produced a Factsheet / Briefing Note on genome editing which is here: http://www.sciencemediacentre.org/genome-editing/
Dr Dusko Ilic: “I declare no conflict of interest”
Prof. Azim Surani: “I have no conflict of interest with this publication”
Dr Christophe Galichet: “I have no conflict of interest.”