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Fertile ground
Male fertility rates could be lifted by new research .
By Wade Zaglas
Research conducted by the University of Newcastle has revealed “ previously misunderstood effects that sperm RNA has on an embryo ” — a discovery that could potentially change fertility treatment for males and fundamentally change science ’ s understanding of human reproduction .
Up until now , reproduction centred on the notion that DNA is “ solely responsible ” for influencing the traits of offspring . However , new research conducted at the university has strengthened the idea that other biomolecules , such as RNA or epigenetic factors , play key roles in governing both male fertility and embryo quality .
The research team uncovered that environmental stressors , such as pollutants that enter our bodies , “ disrupt sperm RNA which could then have a detrimental effect on or be lethal to the embryo ”.
Dr Geoffry De Iuliis , Dr Shaun Roman , Professor Brett Nixon and PhD candidate Natalie Trigg comprise the research team . Trigg is the lead author of the paper outlining their research , which has been published in Cell Reports .
Their research highlights “ that common environmental factors ” that have hitherto been shown to not affect DNA may still have an influence on reproduction due to the influence they have on RNA .
To illustrate this point , De Iuliis cites the example of exposure to radio frequency electromagnetic energy , which is 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 ,” De Iuliis says .
“ 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 .
“ 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 The research team used a chemical – acrylamide – found in small quantities in everyday foods such as chips , toast and particular countries ’ drinking water “ as a stressor on sperm ”. They were then able to conclude that an environmental factor can have an effect on “ 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 ,” 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 .”
The experiments involved sperm being exposed to the acrylamide both while in the testis and after it had left the testis , maturing in the epididymis . Only the sperm exposed after it had left the testis had a deleterious effect on the embryo , and in many cases it was lethal .
“ 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 ,” 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 .”
The researchers importantly note that the levels of acrylamide used in experiments were far more than an individual could consume through their diet , and therefore don ’ t suggest that men change their diet for the time being to avoid the chemical .
Another key point Nixon highlights is that “ sperm RNA returns to normal ” following a relatively short period of ceasing the 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 ,” he said .
“ 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 ,” Roman adds .
“ 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 .” ■
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