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Scientists have managed to produce mouse pups , i.e. bimaternal or bipaternal, in experiments that have been published in Cell Stem Cell.

In the aforementioned study, fertile mice were obtained from two females, and mice from two males were born from surrogate mothers, although they only survived for two days. The strategy consists of using a type of stem cells  (hESCS: haploid embryonic stem cells, which contain half the number of chromosomes [haploid, 1n], such as sperm cells and ova) and a gene editing system — in this case CRISPR — to release these cells from their specific sexual imprinting, so that they can complement a gamete of the same sex. In mammals, because some maternal or paternal genes are deactivated during germ line development (which is known as genomic imprinting), offspring that do not receive genetic material from a mother and a father experience developmental abnormalities or are not viable. The technique investigated to overcome this barrier that prevents reproduction between members of the same sex consists of removing that imprinting.

It is not entirely accurate to talk of exclusively male reproduction, as the cells must be injected into an “environment” that requires the female contribution, and the embryos must then be implanted into a surrogate mother

Healthy pups that were fertile from same sex parents !

Previous experiments had already managed to obtain offspring from two females, but the resulting mice had developmental problems. To resolve these, this time the imprinting was deleted in three regions instead of two. The hESCs thus modified were injected into normal oocytes, and the resulting embryos gave birth to healthy pups that were fertile when they reached adulthood.

To generate mice from two males, six imprinting regions were first deleted, and the resulting cells were injected together with sperm into an enucleated oocyte. However, the resulting embryos died shortly thereafter, hence the strategy was refined: from the embryos thus produced, stem cells were obtained, now diploid. These were used to generate the bipaternal mice using tetraploid complementation  (each one diploid, 2n), these two cells are fused by electrofusion, obtaining a tetraploid cell embryo, 4n; when this develops to the blastocyst stage, the diploid stem cells with no imprinting are injected into it. The embryo will develop normally; the fetus is derived exclusively from the ESC, while the extra-embryonic tissues are derived exclusively from the tetraploid cells. Twelve live pups were thus obtained, but died shortly after birth, with suckling and breathing difficulties among other complications. The strategy was therefore refined a little further, deleting an additional imprinting region (Gnas) and achieving a slight improvement in the health of the resulting pups. In should be mentioned that, in this case it, is not entirely accurate to talk of exclusively male reproduction, as the cells must be injected into an “environment” that requires the male contribution, and the embryos must then be implanted into a surrogate mother.

It is still a long way to go to use these techniques in humans

Although we cannot yet think of an imminent use of these techniques in humans, this study is a proof-of-concept of the technical possibility of crossing the barriers of beparental reproduction in mammals.

From an ethical point of view, conducting these experiments in mice cannot be considered morally reprehensible, provided that the standards for preserving animal wellbeing are met as far as possible, and given that this research is very useful in advancing knowledge of genomic imprinting, among other things.

Ethically  the use in humans of this reproduction techniques would be completely unacceptable

Nevertheless, it is important to mention that this use in humans would be completely unacceptable; first, because of the manipulation and destruction of human embryos that would be carried out to refine the technique, and subsequently, in the selection of the most valid ones;  and second, because it does not seem justifiable to subject the resulting children to the serious health risks that these techniques pose, simply because of a desire to procreate with a person of the same sex (the wellbeing of the child takes priority over reproductive autonomy).

Photo: Cell  Press



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