The future of male infertility
Dr Eoghan Cunnane speaks to June Shannon about his cutting-edge research, which could be used to help develop treatments for male infertility
Dr Eoghan Cunnane, Associate Professor in Biomedical Materials Engineering and Principal Investigator at the Bernal Institute
The future of male infertility
Dr Eoghan Cunnane speaks to June Shannon about his cutting-edge research, which could be used to help develop treatments for male infertility
Dr Eoghan Cunnane, Associate Professor in Biomedical Materials Engineering and Principal Investigator at the Bernal Institute Pictures: Sean Curtin/True Media
Researchers at University of Limerick are working on developing a preclinical model that can be used to test much-needed treatments for male infertility, the global burden of which is steadily increasing.
The World Health Organisation (WHO) has defined infertility as “a disease of the male or female reproductive system, defined by the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse. It can cause significant distress, stigma, and financial hardship, affecting people’s mental and psychosocial wellbeing.”
The WHO estimates that approximately 17.5 per cent of the adult population -roughly 1 in 6 worldwide- experience infertility. In Ireland, it affects one in six couples and despite being categorised as a medical condition it still carries a great deal of stigma and distress for those affected.
Approximately a quarter of infertility cases are due to sperm problems; a quarter are female-related; another quarter are completely unexplained; and a further quarter would be as a result of several different issues, including male and female factors.
Dr Eoghan Cunnane, an Associate Professor in Biomedical Materials Engineering and Principal Investigator at the Bernal Institute, is looking at ways to develop potential treatments for male infertility, rates of which have been increasing worldwide.
Dr Cunnane’s research involves understanding how the cells and tissues of the testicles interact, and how to accurately represent these interactions outside the body in a preclinical model which can then be used to help develop treatments for male infertility.
Non-obstructive idiopathic azoospermia
Dr Cunnane’s research is focused on non-obstructive idiopathic azoospermia where there is no clear explanation as to why the testicles are not producing sperm.
Currently, the treatment for non-obstructive azoospermia involves the male undergoing surgery where tissue is surgically extracted from the testicle to check for sperm cells.
The procedure, known as microsurgical sperm retrieval from the testicle or Micro-TESE, involves surgeons removing small areas of testicular tissue to be examined for the presence of sperm cells which if present can be used for IVF treatment. According to Dr Cunnane, even after such an invasive procedure unfortunately there is no guarantee that sperm will be found.
There are also some pharmaceutical treatments for idiopathic azoospermia but Dr Cunnane explained that these were empirical, meaning that there is no mechanistic understanding or scientific basis for their use.
Therefore, he is planning to develop a representative preclinical model of testicular tissue that can be used to test pharmaceutical treatments for men with this condition which could also potentially remove the need for such invasive surgery.
of the adult population worldwide experience infertility
What we are trying to do is to develop a platform to mechanistically understand why a pharmaceutical agent should be prescribed, how and what should be prescribed, what dosage should be prescribed, and for what duration it should be prescribed
In essence, Dr Cunnane aims to develop a model system of the testicles or a functional unit of testicular tissue which he said needs to be “representative of the native tissue, while also producing scientific results that are reliable and reproducible.”
To develop a representative, reliable and reproducible model, Dr Cunnane and his team must first study and understand the processes that are happening within the testicular tissue itself and for that, they analyse real tissue samples from donated material.
“The tissue is essential to the project because if we want the final model to be representative, we first need to understand the native tissue. We also need our model to incorporate primary cells and extracellular matrix components from this tissue,” He explained.
Donated material
The research project has several streams of donated material one of which interestingly comes from by-products of transgender surgical procedures in Germany.
Following transgender male-to-female surgery, the testicles are considered waste products therefore patients are consented before surgery to allow the tissue to be used for research. Dr Cunnane receives donated material tissue from additional sources including from males who have undergone surgery for testicular cancer.
The team are also beginning to work with collaborators around receiving pre-pubertal testicular tissue from young boys undergoing cancer treatment in the hopes that they can potentially help develop a solution to allow them to have children later in life, as treatment of childhood cancers can often lead to infertility in later life.
Dr Cunnane explained that currently if a man has to undergo cancer treatment, and he wants to preserve sperm he can just donate and store it. However, that is not possible for very young boys who have not yet reached puberty as they are not yet producing viable sperm cells.
Another possible future application of Dr Cunnane’s work would be to take adult stem cells from infertile men and induce them to become germ cells which in turn could become viable sperm cells.
“They have no option other than the extraction of actual testicular tissue and storage of that tissue because we don't have a platform yet for taking immature human testicular tissue and inducing it to produce mature sperm cells. So …another potential use of this platform is to take that immature tissue, extract the cells and tissue components and allow the cells to mature in this platform… and… with the right stimuli and the right environment, you could possibly induce those pre-pubertal spermatogonial stem cells into mature sperm cells that are capable of fertilisation. And wouldn't that be fantastic for these boys who need to undergo chemotherapy?” he said.
Another possible future application of Dr Cunnane’s work would be to take adult stem cells from infertile men and induce them to become germ cells which in turn could become viable sperm cells.
“It's clear that we don't have all the pieces of the puzzle because we're not able to induce spermatogenesis in vitro for humans yet….. if we were to have the right pieces of the puzzle, if we were to understand the right environmental factors, the right stimuli that the cells need in order to be induced from spermatogonia stem cells into a spermatid, then we could represent that in an in vitro model and eventually induce cells from patients who need viable sperm cells,” he explained.
So what does the future of treatments for male infertility look like?
According to Dr Cunnane, for infertile men, the future would hopefully offer a pharmaceutical option that would induce viable sperm production, or it may be that infertile males’ adult stem cells could be induced to become viable sperm cells. For pre-pubescent boys who undergo chemotherapy, the future may offer an in vitro platform to mature immature testicular tissue so viable sperm cells can be extracted.
Whatever the future of treatments for male infertility, Dr Cunnane said success would require a lot of collaboration from across a range of specialists including clinical experts in fertility, embryology and surgery.
He acknowledged that there was already a lot of collaboration in the area of male infertility and added: “Maybe there is potential for biomedical engineering solutions to come in as well and offer clinical tools for helping patients or pre-clinical tools for developing more effective treatments. So I think that continued collaboration is the future there.”
Another possible future application of Dr Cunnane’s work would be to take adult stem cells from infertile men and induce them to become germ cells which in turn could become viable sperm cells.
