26 August 2022

Chimeric spermatozoa

Scientists forced an infertile mouse to produce rat sperm

Anna Novikovskaya, Naked Science

Pluripotent stem cells (PSCs) — a powerful biomedical tool, but obtaining gametes (eggs or spermatozoa) from UCS is an extremely difficult task. Modified gametes most often turn out to be less viable than the cells of the host animal, therefore they lose out in competition during fertilization.

One of the possible solutions to the problem is the blastocyst complementation method. The bottom line is that the stem cells of one animal are planted in a mutant embryo, in which an organ does not develop. As a result, in a mutant animal, an organ develops from the provided stem cells, and, say, mouse kidneys develop in the rat's body.

Now researchers have wondered if it is possible to obtain rat sperm in the body of a mutant mouse, which is infertile in itself. In order to test this idea, they injected rat PSCs into mutant mouse embryos (they had the Tsc22d3 gene, which is critical for sperm development, turned off) to get mouse-rat chimeras.

Rat stem cells developed together with mouse cells, resulting in the appearance of a chimeric animal carrying DNA of two species. As a result of a genetic mutation that causes infertility, the spermatozoa of the mouse itself did not develop, so their place was taken by rat PSCs developing into rat spermatozoa. 

The spermatozoa turned out to be viable and were able to fertilize the eggs of rats (even if it took them longer than "normal" cells), but scientists could not get live rats.

chimeras.jpg

Nevertheless, this work is the first proof of the possibility of obtaining gametes of one species in the body of another. 

If researchers manage to get live cubs from pluripotent stem cells, such a method can be used to preserve rare and endangered animal species and in biomedical research — for example, when modeling hereditary human diseases.

The study is published in the journal Stem Cell Reports (Zvick et al., Exclusive generation of rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells).

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