A new sperm separation technique may one day allow prospective parents undergoing IVF to choose whether they have a boy or a girl before fertilisation takes place, researchers say.

Scientists in Japan have reported a new method which allows them to separate mouse sperm carrying an X chromosome from those carrying a Y chromosome, meaning that sperm can be selected based on whether they will result in female (XX) or male (XY) offspring when used to fertilise an egg.

The researchers say they made their discovery as part of a project to unpick and understand the differences between sperm carrying an X chromosome or a Y chromosome, noting that the former carries far more genes than the latter.

“This is first study to scientifically [show] the functional differences, [ie] fertilisation ability, between X-sperm and Y-sperm,” said Masayuki Shimada, co-author of the research from Hiroshima University.

The scientists say their work could also prove useful in agriculture. “In a dairy farm, the value of a female dairy cow is much higher than male, because milk is only produced by female cows,” said Shimada. “In the case of beef meat production, the speed of growing is much higher in males after castration than females.”

While there are already existing methods such as flow cytometry that can be used to sort sperm, these are based on the relative size of the X and the Y chromosomes and are expensive. By contrast, the latest findings are based on differences in the movement of the two types of sperm, which the team suggests may be a cheaper and simpler technique.

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Writing in the journal Plos Biology, Shimada and colleagues report how they exploited the fact that X chromosomes bear far more genes than Y chromosomes and so can produce a different range of proteins, including certain receptors that can bind to specific substances.

The team focused on two of these receptors, called TLR7 and TLR8. Both bind to a drug called Resiquimod – an antiviral and antitumour agent.

The scientists found that when they exposed mouse sperm to a solution containing this drug, the velocity of some of the sperm was suppressed. The drug also reduced the percentage of sperm that, when placed in a test tube, swam upwards towards a nutrient-rich layer.

As expected, it turned out that Resiquimod was specifically affecting the sperm carrying an X chromosome. However, the team found that Resiquimod did not damage these sperm or their ability to fuse with an egg.

The researchers say their work suggests that by binding to the TLR7 and TLR8 receptors, Resiquimod affects the production of a substance called ATP that transports chemical energy around cells, lowering its levels and thereby reducing the swimming abilities of sperm with an X chromosome.

Similar results were found for another drug that only binds to TLR7 receptors.

The team found the method could be used to skew the odds of male and female offspring in mice.

When sperm that swam upwards were used in IVF, 68 out of 77 embryos had an XY combination of chromosomes and, when 30 of these were transferred to mice, 83% of pups born were male. When samples enriched in X-chromosome sperm were used for fertilisation, the majority of embryos were XX and more than 80% of pups born were female.

Shimada said the process may be applicable to humans and other species if the receptors are found to be present on human sperm.

The team acknowledges that the possibility of using the technique in humans comes with ethical problems, though these are not new. Embryos produced through IVF can already be screened for their sex. While in some countries including the US parents can use this to choose the sex of their child, in the UK it is illegal to select which embryo to implant based on its sex unless there are medical reasons.

Prof Robin Lovell-Badge, an expert in developmental biology at the Francis Crick Institute in London, said the research could prove very useful if similar effects are seen in farm animals. He added it may also help solve the puzzle of why, even in nature, sex ratios in some mammals can shift away from 50:50 under certain environmental conditions, noting there is some evidence that in humans stress can have such an effect.

“While the mice born after the sperm sorting apparently appeared normal, it would be essential to verify that there were no long-term effects of activating these receptors prior to fertilisation,” he said. “In other words, do not try this at home in attempts to bias the likelihood of having a boy or a girl.”



• The headline of this article was amended on 16 August 2019 to refer to sex, rather than gender, selection.