15 September 2016

Partial parthenogenesis

Is fertilization possible without fertilization?

Kirill Stasevich, "Science and Life"

Both the sperm and the egg (oocyte) are extremely specialized cells with a specific function: they must merge together, combine their genomes and start the formation of a new organism. At the same time, the sperm, for example, completely "forgets" who it was – it is no longer a floating cell that strives for a well-defined goal, it is already just the paternal half of the genome. Such dramatic changes, as it was believed until now, in the male germ cell occur under the influence of the egg.

But researchers from the University of Bath and the University of Regensburg came up with the idea to check whether an already fertilized egg can also control a sperm? After all, after fertilization, the egg is no longer an egg, it is already the first cell of the embryo with a double set of chromosomes, that is, a single–celled embryo that is about to begin dividing. Can an embryo perceive genetic information from a sperm? To test this, Anthony C. F. Perry and his colleagues launched a parthenogenetic development program in mouse oocytes, when an unfertilized oocyte is processed in a certain way, turning it into an embryo. That is, strictly speaking, there is no fertilization here, but the embryonic development program works the same way as with fertilization. Such a parthenogenetic embryo remains haploid, that is, all the chromosomes in it are only in one copy.

The development of the embryo begins with the fact that its very first cell doubles the genetic material and divides in two. In the experiment, after the parthenogenetic egg had made a copy of the DNA and was ready to begin dividing into two cells, a sperm was injected into it. Now there were three sets of chromosomes in the embryo: two from the egg, which doubled the DNA but had not yet split, and one from the sperm. During division, chromosomes are known to diverge in daughter cells, and in this situation, the chromosomes could scatter in different ways. However, cells that would get only one chromosome set (whether male or female) would simply not be able to develop further. The same applies to those who would get both female copies, that is, who would remain parthenogenetic embryos – such a scenario in the case of mammals after several cell divisions ends with the death of the embryo. So there was a chance only for those cells that, after division, received one chromosome set from the egg, and the second, later, from the sperm.

That is, the sequence was as follows: at first, the egg was provoked to parthenogenesis, so that it ceased to be an egg and began to prepare for division, but before it was divided, a sperm was still introduced into it. Fertilization here was subjected to an embryo that had already begun to develop, although it cannot be called fertilization, rather, the transformation of a parthenogenetic embryo into an ordinary one. And so, when such embryos were placed in mice, they turned out to be quite normal mice (although only in 10.4%, the rest of the embryos died during intrauterine development). In the future, the mice that were born in such a strange way themselves reproduced safely.

parthenogenesis.jpg
A snapshot from the press release of University of Bath Scientists make mice from non-egg cells – VM

When the sperm merges with the egg, the contents of the sperm, that is, the nucleus with DNA and some cellular organelles, pass into its cytoplasm. The DNA of the sperm is tuned in a very specific way, and this setting persists for the first time after fusion. As is known, the activity of genes can be regulated by the fact that some of them are stored in an "archive" in combination with packer proteins, which are histones in ordinary cells, and protamine proteins in spermatozoa. Such tightly packed genes are inaccessible to other cellular protein machines that read genetic information and bring it, so to speak, to life. In spermatozoa, the DNA is all packed in protamine complexes, and the necessary molecular instructions are stored in pre-synthesized RNA copies. However, during fertilization, special proteins from the egg nucleus come to the chromosomes of the sperm and rewrite the scheme of regulation of sperm genes; now its DNA looks and works differently, now it can be treated as an integral part of the germinal genome. This is how it should be understood that the egg reprograms, changes the sperm (more precisely, its DNA), forcing it to "forget" about its past. Recall that all this happens during normal fertilization, but, as the article in Nature Communications says, literally the same processes occur when the sperm fertilizes without fertilization, that is, when it enters the embryo ready for parthenogenetic development: the proteins of the former egg come out of the nucleus and rewrite the regulation program Sperm DNA. True, the authors of the work note that the molecular "editing" in this case differs from what happens during normal fertilization, but then everything becomes even more interesting: it turns out that regulatory variations at such an important stage of individual development do not prevent a healthy and quite fertile individual from being born.

The general conclusion from the work is that the molecular-cellular procedures that are necessary to "launch" a new life, it turns out, are not something that happens at a strictly defined moment in the life of an egg. The results obtained, on the one hand, expand our understanding of where embryonic development begins and how it happens, and on the other, open up new prospects in biotechnology. After all, it was possible to get an embryo here by "mixing" a sperm with a seemingly ordinary dividing cell – an egg that followed the path of parthenogenetic development divides according to the same scheme as other cells of our body divide: skin fibroblasts, blood stem cells, etc. According to Anthony Perry himself, now we can well imagine an embryo formed from a skin stem cell and a sperm. But still, we should not forget that in the experiments described, an egg was used, which had just ceased to be an egg and became an embryo, and in which some molecular processes could still go on as before, according to the "egg-cell" scenario, and such an embryo is still not skin and not blood. However, such embryos could become not only an object of fundamental research, but also a source of human natural germ cells, which are often forbidden to use due to moral and ethical considerations; it is possible that with the help of, so to speak, partial parthenogenesis, some of the moral and ethical problems can be circumvented.

Portal "Eternal youth" http://vechnayamolodost.ru  15.09.2016


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