Growing up on a dairy and beef cattle farm in Gloucester (NSW), Brett’s parents were in the process of trying to improve their herd. To do this, they were exploring the use of artificial insemination and embryo transfer, which meant a technician visited their farm on a regular basis.
Brett was given the chance to watch the beginning of life down a microscope – the sperm binding to and proceeding to spin an egg in the lead up to fertilisation –and nine months later, he saw the results of this process with the birth of several calves.
From that moment, he was hooked.After a brief post-high school photography career, Brett studied science at the University of Newcastle, going on to do Honours and a PhD in animal breeding technology.
“We were trying to develop a contraceptive vaccine for rabbits to stop them breeding,” says Brett. While the project wasn’t a success, Brett says it spiked his interest in how sperm are transformed into highly specialised cells with the sole purpose of achieving
fertilisation. “We still don’t completely understand how they do that,” says Brett.
After finishing his PhD, Brett was lured to the USA to study his post-doctorate at Emory University in Atlanta, Georgia; a time that he says was exciting and exhausting in equal measure.
“There were post-docs there from all over the world and we worked all day, every day. It was very competitive.”
In 2001, he received an extraordinary offer; to return to Newcastle and set up a program around male infertility, overseen by Professor John Aitken. Brett, who had spent over a decade working on animal models, was now ready to make the transition to humans.
Just like when he was a kid, reproduction continues to captivate him.
“It’s an incredible, arduous feat for a healthy sperm to fertilise an egg. Out of millions of sperm, only a handful are good enough to achieve fertilisation. Over 99.9% won’t complete the journey. I don’t think people realise what a miracle it is.”
But human fertility – particularly male fertility – is potentially in dire straits. “There is really quite compelling, indisputable evidence that sperm quality is in decline. If the current trend continues, there will be significant implications. The rate that it’s happening at indicates that it’s likely environmental – possibly linked to a combination of lifestyle, occupational
exposures, and stress-related signals,” said Brett.
Just one of the chemical groups that Brett’s team is exploring is PFAS (per-and poly-fluoroalkyl substances). While there are(more than 4,500 types of PFAS in regular use, Brett’s team is homing in on the types used in firefighting foams.
They are running a combination of pre-clinical and clinical trials to look at the ways that PFAS found in the groundwater around Williamtown can impact sperm quality and male reproductive health.
Vision for the future
While Brett says that there are certain things men can do to improve the quality of their sperm, he would like to find better ways to diagnose male infertility and ensure that sperm chosen for use in Assisted Reproductive Technology (ART) is of high quality.
“We know that maintaining a healthy lifestyle for a ‘wash out’ period of at least a month is a simple thing men can do to potentially improve their sperm health. But it’s worth noting that semen – even that produced in healthy fertile men – has only approximately 4% of sperm cells that have normal morphology. That’s only one in 25 sperm cells that are potentially capable of fertilisation.
“I would like to see the development of simple diagnostic tests that screen for the extent of DNA damage within a given sperm cell, as well as the identification of protein biomarkers to distinguish functional sperm cells. Ideally such tests could be as simple as Rapid Antigen Tests and allow men to quickly test their sperm health. Even in healthy men, there is enormous variability in the quality
of sperm they produce over the course of a year so this could help them pick a conception window for when their sperm is looking good,” said Brett.
Ultimately Brett would like to see better diagnostics, sperm selection tools and then therapies to address some of the challenges facing infertile men.
“It’s amazing how little we know about the causes of male infertility despite the fact that a male factor is implicated as the major cause in at least 50% of all infertility cases.
Understanding this is not just about perpetuating life, it’s about quality of life for the parents and the children.”