Research at the University of Newcastle has uncovered previously misunderstood effects that sperm RNA has on an embryo – a development that has the potential to change male fertility treatment and fundamentally shift our understanding of the human reproduction process.
A basic understanding of reproduction has previously centred around the idea that DNA is solely responsible for governing the traits offspring will have. This new research helps to strengthen a recent idea that other sets of biomolecules such as RNA, known as epigenetic factors, also play critical roles in governing male fertility and embryo quality.
The researchers found that environmental stressors, for example pollutants that enter our bodies, disrupt sperm RNA which could then have a detrimental effect on or be lethal to the embryo.
The team of researchers include Dr Geoffry De Iuliis, Dr Shaun Roman, Professor Brett Nixon and PhD candidate Natalie Trigg, who is the lead author of a paper outlining their findings that has been published in Cell Reports.
Their study shows that common environmental factors that have previously been shown not to effect DNA may, in fact, still have a role to play in reproduction due to the influence they have on RNA.
Dr De Iuliis gives the example of exposure to radio frequency electromagnetic energy – an environmental stressor emitted by mobile phones and WiFi.
"Radio frequency energy is defined as being non-ionising, which means it can't immediately alter biomolecules, so can't directly create DNA damage. Some conclude that it is therefore safe," says Dr De Iulliis.
"This study opens up the concept that DNA damage is not the be-all and end-all. Perhaps the more subtle RNA changes are important to take note of also.
"Over the last 50 years, some have suggested male fertility has been falling off a cliff. The quality of sperm is certainly going down and the fertility of humans is decreasing.
"Not a new idea, but perhaps what we're seeing is that new environmental stressors that have come about over the past five decades are combining to compromise fertility, but their individual effects are so subtle that we may not see them in isolated research experiments."
The study
By using acrylamide – a chemical commonly found in small quantities in everyday foods such as toast, chips and even some countries' drinking water – as a stressor on sperm, the team discovered that this environmental factor can affect both sperm quality and embryo viability after it has left the testis.
"We're exploring what acrylamide does in terms of damaging the gametes and what that means for future offspring. And this study has shown that it's not just sperm DNA, it's also their RNA that are vulnerable to environmental stressors," Dr Roman explains.
"As the sperm progress from the testis towards the point of ejaculation – a process that takes about one week – they take on some of these epigenetic factors from the male reproductive tract."
In the experiments, sperm were exposed to acrylamide both while in the testis and after it had left the testis and was maturing in a duct called the epididymis. Only the sperm that were exposed after it had left the testis had a detrimental effect on – and, in many cases, was lethal to – the embryo.
The study indicates it is changes in the RNA profile delivered to the sperm in the male tract that pass on the consequences of exposure.
"These exposures change the RNA species that are delivered to the sperm and that alters the genes that are 'turned on' in the resultant embryo," Dr De Iuliis explains.
"It points us away from the dogma that sperm DNA is the only thing we should be concerned about.
"In our field it's common to say, 'sperm are just carriers of DNA, the egg has all the important ingredients that determine the fate of the embryo', but we are now understanding that sperm carry much more than just DNA, including an epigenetic payload, and changes to either after the sperm have left the protective environment of the testis have important consequences."
Importantly, the levels of acrylamide used in the experiments was well beyond the level a human could consume through dietary intake. So, certainly for the time being, there is no suggestion that men trying to conceive should specifically alter their diet to avoid this particular chemical.
Professor Brett Nixon also points out that the sperm RNA returns to normal after a relatively brief recovery period following cessation of acrylamide treatment.
"This finding identifies the critical importance of a male's health immediately prior to conception and adds to a growing body of data that simple lifestyle changes enacted during this window could have major implications for an individual's fertility."
Opening the door for future fertility treatments
This research also opens the door to specific future treatments.
"It provides us with a powerful model to identify the mechanisms of how these epigenetic changes take place and the changes we identify have the potential to be used as diagnostic biomarkers of stress exposure," Dr Roman says.
"Extrapolating from this, the potential exists for screening sperm from any particular male to see if they have these markers of toxicant exposure.
"When you understand the molecular biology, then you can go ahead and design your information strategies, your targeting strategies and your therapeutic strategies. We now have the tools to work out how to target pathways, which we've only just identified in this paper, that lead to these epigenetic or RNA changes. Now we can target the root components of these pathways,which could lead to a therapeutic intervention.
"It opens the door wide."
