Separating X and Y sperm enables sex selection in offspring

Researchers from Hiroshima University have developed a simple, reversible chemical treatment that can segregate X-bearing sperm from Y-bearing sperm, allowing dramatic alteration of the normal 50:50 male/female offspring ratio in mice.

Most cells from male mammals contain both an X and a Y chromosome, but during sperm development (spermatogenesis) the X and Y chromosomes are segregated into different cells so that an individual sperm will carry either one or the other, with an X chromosome giving rise to daughters and a Y chromosome to sons.

Unlike the Y chromosome, which carries very few genes, the X chromosome carries many — some of which remain active in the maturing sperm. This difference in gene expression between X- and Y-bearing sperm provides a theoretical basis for distinguishing the two.

The researchers found that almost 500 genes are active only in X-bearing sperm, of which 18 genes encoded receptors; because of their functions to response to ligand stimuli, this made them good candidates for manipulating the sperm. The team focused on a pair of receptors called Toll-like receptor 7 and 8 (TLR7/8) and found that a chemical that bound to the receptors slowed sperm motility without impairing either sperm fertilisation ability or viability. They showed the effect was due to impaired energy production within the sperm and could be reversed by removal of the chemical from the medium.

Treatment of mouse sperm with this X-retarding chemical, followed by in vitro fertilisation with the fastest swimmers, led to litters that were 90% male — when the slower swimmers were used instead, the litters were 81% female. The results were published in the journal PLOS Biology.

There are currently procedures that can be used to separate X and Y sperm, but they are cumbersome and expensive, and risk damaging the DNA of the sperm. The new procedure thus has the potential to greatly simplify sex selection for either in vitro fertilisation (in which sperm and egg join in a lab dish) or artificial insemination (in which sperm are implanted into the female reproductive tract). Such techniques are widely used in the agricultural animal breeding field, as well as in human-assisted reproduction.

“The differential expression of receptor genes by the two sex chromosomes provides the basis for a novel and potentially highly useful method for separating X and Y sperm,” said lead researcher Masayuki Shimada, who claimed the researchers have already succeeded in the selective reproduction of male or female in cattle and pig by this method. 

“Nonetheless, use of this method in human reproductive technology is speculative at the moment, and involves significant ethical issues unaffected by the utility of this new technique.”

Image credit: ©stock.adobe.com/au/Christoph Burgstedt

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