A revolutionary technique for selecting the sex of embryos

In an ideal world, hens would only sire female chicks, sows would not carry boars and the cows would not give bulls. This would avoid the distressing images of male chicks drowned at birth or animals euthanized because they were unproductive or useless. For many years, therefore, scientists have been trying to find a way to select the sex of embryos before birth, so as to obtain litters of one and the same sex (male or female).

The easiest way is to sort the fertilized eggs and eliminate those of the unwanted sex. It is also possible to sort the sperm depending on the sex chromosome (see our article below) or to introduce a “Suicide gene” on the X or Y chromosome, so as to prevent the development of the embryo of the unwanted sex. But all these techniques are not very reliable, drastically reduce the rate of fertility, and can induce dangerous mutations later.

A lethal gene introduced by CRISPR-Cas9

A team of Francis Crick Institute and the University of Kent now claim to have found a “100%” reliable technique that results in litters only male or female. The researchers, whose study is published in Nature Communications, relied on the editing technique genetic CRISPR-Cas9. The latter is based on two parts: on the one hand the complex enzymatic who will “cut” the uncomfortable, on the other a ” RNA guide ‘which recognizes the target gene and guides theenzyme “Chisel” in the right place. The researchers separated these two parts, placing the gene for the enzyme on the father’s X or Y chromosome, so that it is transmitted to only one embryo sex. They then looked for a mechanism powerful enough to eliminate all of the embryos unwanted sex. The team chose a gene named Topoisomerase 1 (TOP1), essential for cell division: once deactivated, the embryos are killed at a very early stage (16 to 32 cells maximum). The gene targeting TOP1 was introduced into the guide RNA of the female mouse, to which the enzyme complex cutting theDNA and from the male. Thus, when the two parts of CRISPR-Cas9 are brought together during the fertilization, male or female embryos (depending on whether the complex is attached to X or Y) all die prematurely.

Litters giving more embryos

Not only is this technique 100% reliable, killing all of the embryos of the unwanted sex, it is also much safer for the mother, as the embryos die before implantation in theuterus. This leaves the mother with fewer embryos to support, making it more likely that the “good” embryos will develop properly. The other advantage is that since the latter have more space, we do not observe the reduction in the size of the staves as in the other methods (the staves are still reduced by 30% to 40%). No deleterious effects were also observed in mice born using this technique.

Choose the sex of your child?

The experiments here were carried out in mice, but the TOP1 gene being present in most mammals, they could perfectly apply to many other cash, note the authors. Could it even concern humans, raising the risk of parents being able to choose the sex of their child? Theoretically yes, but it is unlikely. First, the process works best with species that have large litters and short gestations, like mice or chickens. On the other hand, the approach requires genetic modifications that are not feasible in humans, the authors stress. No risk of seeing a gene either lethal escape into nature, since the mechanism only works when the two parts of the enzyme complex are brought together. In the end, this method could prevent the slaughter of millions laboratory animals and breeding, insists Charlotte Douglas, lead author of the study. However, prior authorization from the health authorities will be necessary to develop it on a large scale in breeding.

Choosing the sex of your child: a new method could make it possible

Article by Celine Deluzarche published on 08/26/2019

Researchers at the University of Hiroshima in Japan have just discovered a new ultra simple and apparently very reliable method for sorting sperm X and Y and thus choose the sex of the embryo. A technique that could lead to a demographic imbalance in certain countries where the male sex is valued.

The X chromosome, almost three times the size of the Y chromosome, also has many more genes (3,000 versus 700). Nevertheless, these differences so far did not appear to affect sperm behavior and therefore did not allow differentiation of sperm without performing advanced genetic analysis. Yet this is what Masayuki Shimada and his colleagues have achieved. By performing detailed DNA sequencing of mouse sperm, they discovered 492 genes active in sperm X which are not expressed on Y spermatozoa. The researchers then refocused their interest on 18 of them coding for receptors located on the surface of the spermatozoon, with the aim of being able to manipulate them from the outside.

A success rate of between 81% and 91%

They noticed that two receptors, named Toll-like receptor 7 and 8 (TLR7 / 8), could modify the production ofenergy sperm X when they bonded to a molecule chemical called Resiquimod (R848), which slows down the sperm mobility without affecting its other functions. It was therefore enough for them to immerse the sperm of mice in a chemical bath containing this molecule to “sort” the spermatozoa according to the sex chromosome. By selecting the fastest sperm, they obtained 90% male embryos. The sperm artificially slowed down giving them 81% female embryos, according to the results of their experiment, published in the journal PLOS Biology August 13.

There are already different techniques for sorting sperm. The most reliable is to review the genetic code of each sperm. It is also possible to “stain” the sperm with a fluorescent dye, where the Y sperm containing less DNA material then appear less bright than the X sperm. However, these two methods are expensive and require specialized equipment. Other experiments have also been attempted such as exposure to high temperatures or low pH, but with a risk of damaging the DNA of the sperm.

Pre-implantation diagnosis, banned in France for IVF but authorized in the United States

The disconcerting ease of implementing the method developed by Masayuki Shimada raises many ethical questions. In France and in many countries (India, China, Australia, Canada, etc.), the pre-implantation diagnosis (DPI) allowing you to choose the sex of your future child is strictly prohibited for fertilization in vitro (IVF). But the principle is completely legal in the United States where wealthy couples resort to it. This method being very inexpensive, one can fear that it spreads in the countries where the male sex is privileged, like in India or in China, resulting in a demographic imbalance. According to a report by the Indian government published in 2018, abortions selectively have caused a “shortage” of 63 million girls in the country.

A myriad of natural methods to choose the sex of your child

Masayuki Shimada defends himself against such projects and claims to have developed his technique for cattle. ” We have tested the sorting on calf and pig embryos with success, assures the researcher. The use in humans is purely speculative and we do not know at all if this could work. “, He explains, acknowledging however that this would pose an ethical problem.

In the meantime, women wishing to choose the sex of their child have at their disposal a vast panoply of more or less eccentric methods. L’application My Bubelly thus offers a personalized diet according to the desired sex. The site explains in particular that a vagina more acid promotes the passage of X sperm while a more alkaline vagina promotes the passage of Y sperm. The app sells “girls boxes” and “boys boxes” containing special food supplements and ovulation tests making it possible to target the right niche for the conception of the baby. She claims a success rate of 90%, even though no scientific study supports this method.