#02 - Dr Geoffry De Iuliis - The Sperm Crisis: What’s Really Driving Male Infertility?

Infertility rates across the developed world are on the rise — and around one in six Australian couples will face fertility challenges. A major part of the problem? A decline in sperm count and quality.

In this episode, I’m joined by reproductive biologist Dr. Geoffrey De Iuliis, whose world-leading research is uncovering the hidden factors behind male infertility. From oxidative stress and environmental toxins to the potential effects of mobile phone radiation, Geoff’s team is asking the hard questions: Why does infertility occur in some men? How can we treat it? And what lifestyle changes can protect fertility?

We dive deep into the science of sperm health, exploring how damage at the molecular level can sabotage fertility and how social factors are pushing younger generations decisions to conceive back later and later.

Whether you’re planning a family, working in health, or simply curious about how modern life is impacting men’s biology, this conversation sheds light on a silent crisis and where the science is taking us.

Transcript

SPEAKER_01 0:01

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SPEAKER_00 0:50

Sweet. Jeff, welcome to the show. Thanks very much for having me.

SPEAKER_01 0:56

So you're a reproductive biologist and a researcher at the University of Newcastle. And you specialise in male infertility?

SPEAKER_00 1:04

Yeah, that's right. Yeah. What got you into that? Very indirect. Um, so born and bred in Newcastle, did my science degree there. And I I loved chemistry actually. Um and then I I went and did all my studies in chemistry. I did a PhD in chemistry actually, and was ready to go to Heidelberg to to do a postdoc position over there. I got a kind of an email or uh got contacted by this person named John Aitken. Didn't really know much about him at the time. He invited me for a chat and he had a job opening up. And then I found out that he is a very big name in male reproduction from England, but moved to Newcastle and set up a group, and he's still with us. He's retired, but he's still still working, and offered me a job. So I couldn't knock it back in my hometown. Um, and he was looking for a chemist that could help out sperm cell biology, and so here I am. Here we are. There you go.

SPEAKER_01 1:59

And I know your is it your family that has a history in wineries? Yeah, that's right. Did that play a role in in chemistry at all?

SPEAKER_00 2:07

Yeah, yeah. So my cousin and I are a similar age. Um we both did a Bachelor of Science. He went to Sydney and did it at Macquarie Inn while I did it, did it in Newcastle. And yeah, we were both brought up in that kind of field. Um, you know, the they bought the vineyard, you know, both when we were young teenagers, and we spent well, he spent a lot more time there, but I was spent every two two weeks there, you know, every second weekend. Yeah. And then he decided to go on and and be a winemaker, which worked out fantastic, and he's he's absolutely killing it.

SPEAKER_01 2:36

Yeah, awesome. So we're gonna talk a bit about infertility today. Yeah. I know there's a lot of misconceptions kind of around the fertility subject. Just to start us off, how do we actually define infertility?

SPEAKER_00 2:50

So, yeah, so I suppose one of the things that people may not know is that getting conceiving naturally actually takes some time. So every round, if you if you like, um, there's about a 25% chance of of conceiving for the female to become pregnant. And that's very, very normal. Um, so given those kind of odds, uh, we usually say between six months to a year of trying to become pregnant. And if that doesn't happen, so you know, if you're trying for six months and it's not happening, that's no reason to stress. But then beyond a year is when you can start, you know, getting some advice around that and seeing a GP and then a fertility specialist.

SPEAKER_01 3:29

So I think at least in my experience, there was a lot of can misconceptions, uh, even just a few years ago, that infertility was kind of mainly driving from the female side. I know there was a lot of stigma around that too. Yeah. More and more research is kind of coming out now. Is it moving to the 50-50 male-female kind of contributions?

SPEAKER_00 3:49

Yeah, no, you're absolutely right, Ed. So you know, the the the burden of infertility was historically always placed on, you know, on the female. What we are now finding, um, which really makes complete sense to me, given there's two people that are uh required to to do this, is that it is largely 50-50. And what that means is that the science for male infertility is well behind the female, because all the science was geared towards uh, I suppose, fixing female fertility. And now that we understand, again, makes sense that half half of the reason why a couple might be infertile is due to the the male. Again, the science is a little bit lagging. Um, so there's many unknowns around you know sperm cell biology and and other things, which is I suppose what we concentrate on as researchers.

SPEAKER_01 4:39

The first thing that kind of comes to mind for me, a bit of a funny example, would be uh Robert De Niro. I know he had a kid, I think it was 79 years old or something. How much is it that age plays a role? Because I know we talk about kind of high risk pregnancies for women, yeah, and we're talking around the 35-year-old mark. I think the correct term for it is advanced maternal age.

SPEAKER_00 5:04

Yeah, and and so and sometimes called geriatric pregnancies.

SPEAKER_01 5:08

Yeah, which for someone that's 35 I think would be shocked to hear. And then we hear about stories of you know males having kids at 79. How much does age, and we'll dive into this more later, how much does age kind of play a role in sperm cell health and and conception as a whole?

SPEAKER_00 5:25

Yeah, really good question. So uh most people know that female health, uh female reproductive potential drops off um with age, and that's because they largely because they have a finite pool of of eggs which wane as uh during the course of life. Uh the male situation is completely different. We're continually generating new sperm cells all the time. So, you know, roughly about a thousand sperm per second is uh a male is making. And that actually only slightly slows down as a man ages. Um in I think the oldest man I know of was like 93 or something like that, who's uh who's fathered a child. So it's certainly possible to father a child at an older age, but what we do know is as a male ages, then the quality of the sperm that they produce starts to become lower and lower. And yeah, we can get into a bit more what the consequences of that are. But yes, certainly uh a a man can father a child at an older age, but there are potential risks involved with that.

SPEAKER_01 6:22

Yeah, definitely. I think just to throw some stats at it, uh I did some research last night actually. Yeah. And I found the WHO reported that one in six people are now kind of globally facing infertility problems and sperm counts as a whole from 1970s have dropped 50%. Yeah. What are the kind of bigger environmental society kind of factors do you think that's contributing to it?

SPEAKER_00 6:49

An alarming thing is that that the people that they're talking about are in the fertile window, you know. So these are not necessarily the the people of advanced age. So this is a whole nother uh issue, is that you're looking at young, healthy uh men, if it were focusing on the males, that have absolutely right, is a clear decline in the amount of sperm they're producing. There is ongoing evidence to s to say that the the quality of the sperm they're producing is is declining from, you know, if you would 20 years ago, if you went and did a semen test, you know, you're struggling to get pregnant with your partner, you'd go and get a a test done. Usually what the the andrologist who's the person who who does that, those kind of measurements, would be looking at something like 200 million um cells per mil in the ejaculate, that has now been revised down to 20 million per mil. So uh 10 times lower than what it was. And that that is but that's just a fact that you know normal fertile men produce on average about 20 um million uh cells per mil, whereas you know, that used to be a lot more. Um and that that evidence is very clear.

SPEAKER_01 7:58

Yeah. Is it the same for women? Are women having fertility issues just as much?

SPEAKER_00 8:04

Yeah, it's uh interesting. Um, our our c thought is that certainly what we know is that female infertility is the largest driver of that is advancing age. That's that is very clear. The things that are driving male infertility, it is not as clear as that. It seems to be some interaction with the environment, the lifestyle that's affecting the man's fertility. Biologically, it does make some sense to us that, you know, when uh when a male produces a mature sperm, they're very, very different to any other cell in the body. They're the smallest human cell. The egg is the largest human cell, by the way. Sperm is the smallest human cell. Because of their uniqueness, they are much more vulnerable to external pressures than our normal cells might be, you know, like our skin cells or or whatever. So this means that they might be more vulnerable to novel environmental pressures. Um, you know, we we can get into some of those um if you like.

SPEAKER_01 9:05

Yeah, definitely. We'll definitely be diving into that. What is the optimal time uh biologically? Like I know people, societal expectations will kind of push you to have kids later. Yeah, but biologically, where's the window?

SPEAKER_00 9:19

Yeah. John, who I mentioned right at the start, who you know is still a very important mentor for me, um, he provided some information uh and has given numerous talks around this. And he uh has this wonderful slide where he looked at the traditional tribes, hunter-gather gatherers, and looked at their reproductive habits. And it was basically uh what we think is reflects the optimum optimal time for reproduction. And for those people, uh they start childbearing at around 19 years of age and then go on to bear usually five to six children over that time, which ends roughly around 32 years of age. So that that kind of span between kind of 20 and 32 for a female. For a man, uh you know, we get off more easily again. Um, you know, that that again happens from a similar age, 19, but really we don't see any significant declines in fertility, generally speaking, until a man hits around the age of 45 to 50. Yeah, definitely.

SPEAKER_01 10:17

It's interesting because I think obviously society isn't geared to even support individuals for having children that young that young. But biologically we're on such a different clock. It's uh it's an interesting conversation for sure. Yeah. Outside of age, we're seeing these kind of clear links between fertility and factors like toxins, diet, obesity, stress, and even just a sedentary lifestyle. Yeah. Are those the main drivers? What are we looking at?

SPEAKER_00 10:46

Yeah, I mean, uh again, it makes a lot of sense to me. You know, why would male fertility be declining only just now? You know, we've been around for millions of years, right? So why are they declining over the last 50 years? So an obvious answer to that is that the novel factors that we are now exposed to, which we were never exposed to before, could be having an effect on our fertility. And that also makes sense to us biologically because we know sperm cells are very sensitive because of their unique uniqueness. They are sensitive. So that's these are the kind of things that we're exactly studying. We're trying to understand what what factor, what factors, more likely, it's a combination of factors that are leading to the decline in in sperm quality that we're seeing. So, generally speaking, and I think we can talk about this later if you like, but generally speaking, what we do certainly know is the general health of a male will reflect reflect their uh fertility potential um and their ability to create the best possible quality um sperm.

SPEAKER_01 11:49

So when we talk about health, and we kind of mentioned this before we started the podcast, are we talking about cardiovascular health, diet health? Uh, what are we talking about? Is it overall health? How how do you actually measure that?

SPEAKER_00 12:01

Yeah. So again, it's a a field that's uh being worked on very heavily heavily at the moment within the reproductive sphere. But our our knowledge so far is that general health seems to align with reproductive health for men. Again, something that does seem to make sense if you're in an environment where you can be healthy, where you can have a balanced diet, where you can be f uh somewhat free of stress, then it would make sense to be fertile at those those times. Whereas if you are unhealthy, you don't have access to the right foods, uh you're going through very stressful environments, perhaps that's not the right time to be bringing a new generation or a new individual into the into the plan, if you like. So yeah, uh we do find strong evidence to say that if a man suffers from things like diabetes from cardiovascular health issues, then generally speaking, again, there's a very close link to a poorer fertility. We don't know the mechanisms about how that how that plays out. We do have some ideas for sure. We may talk about one of those later, but certainly there's a strong link.

SPEAKER_01 13:10

We want to jump into oxidative stress. You've done a lot of work kind of linking that to damage in sperm cell DNA. Yeah. Can you give us an overview of what it is? Just a broader kind of picture so we can dive into it more.

SPEAKER_00 13:21

Yeah, so oxidative stress is uh essentially like a chemical imbalance in our cells. Our cells produce energy um to get things done. And uh just happens to be a byproduct of that is some of these what we call reactive oxygen species. And that's completely normal. Um, however, the stress, the oxidative stress occurs when those factors, those molecules, tap start to take over um and become too abundant. And that's when a cell would uh come into a state of oxidative stress. So some people may have heard that, you know, uh there's plenty of research to suggest that that cumulative stress, oxidative stress, is why we age. Along with that is the explosion of supplements that are antioxidants, right? That are meant to suppress that oxidative um stress and keep us young. You know, that's that's the the science behind it. So sorry, that's the thought behind it, not necessarily the science. Um that's what oxidative stress is. It's essentially um an imbalance that can damage the cells. And what we've found as a group and what I've been really interested in and focused on in my career is to understand that oxidative stress, how it is created in the male reproductive tract and in the sperm cell. So actually, one of my first papers as a young researcher was to prove using my chemistry now to prove that these reactive oxygen species were actually produced in the sperm. Um so that was a that was a lovely thing to be able to contribute to the field. And what we're now under what we're now understanding, or at least our hypothesis, is that that may be a central mechanism that is linking things like age, things like environmental toxicate uh toxicants, um, environmental factors, mental health, stress, those things may be all working through oxidative stress in the male reproductive tract that then leads to the poorer quality of sperm that we're seeing. And importantly, that oxidative stress is quite uh impactful for the DNA, as you mentioned. So again, you don't, you know, I say this all the time, no one has to be a reproductive biologist to understand that if you damage the DNA in either the sperm or the egg, then that's you know, uh that's not a good thing.

SPEAKER_01 15:33

Yeah. Yeah, I think uh when you kind of look at the research you've done on oxidative stress, and you mentioned earlier, like what's the difference between sperm counts and you know, 50 years ago and why we're having issues now. And I think that's definitely something that's probably more prominent in our world is just stress and the way that we're kind of steering society towards more of a you know, sedentary, more efficient is probably the word people would use day-to-day lifestyle. I read and I kind of wanted to ask you this myself is excessive exercise a factor in uh oxidative stress?

SPEAKER_00 16:11

It can be. I am certainly not an expert in exercise science, but I suppose anything outside, especially if it's if it's chronic, um, is detrimental to to male infertility. So if it's chronic exertion over and what I'm talking about chronic is I'm talking about, you know, weeks and months. Again, you know, males get out of the reproductive situation pretty easily again, because the the beauty of the male reproductive system is that if if you go through a higher a high period of stress and you may damage your sperm, the stem cells that repopulate those sperm are very robust, actually. And because we're generating new sperm all the time, thousand again, I mentioned thousand a second, then if you overcome that stress, so you can settle down, you can become healthy, you you know, remove yourself from whatever exposures that might be damaging, regain some better mental health, then uh theoretically those sperm cells should reflect that and and over the the course of two months or so um should come back to normal. And we do see this happening all the time.

SPEAKER_01 17:19

So when we talk about sperm cell damage, we can have damage to the system that's permanent and not permanent. How do we differentiate that? Is it like a physical injury that would cause permanent damage, or is it like these external factors, oxidative stress?

SPEAKER_00 17:35

That's a really good question, Ed. Um, yeah, so certainly, you know, if if a male presents to be infertile and produces low number of sperm, usually the reasons for that, there are some rare reasons that are unknown, but usually the reasons are very straightforward, such as blockages in the male reproductive tract, right? Now I mean that's not great news for people, but it's actually something you can do something about. Um you can you can remove those blockages. When you don't know why someone's not producing um sperm, then that becomes much more difficult to address. So those kind of more permanent issues, uh generally speaking, some of those are easier to fix. There are some rare situations where they're not. There can be genetic issues that are typically reasonably rare where that's more problematic to fix. But certainly, you know, if it's a most of the problems can be transient. And that's why we promote good male health. Because, you know, even if a situation where I mean, you know, cigarette smoking is a is a massive one, that was that's been so robustly proven that a man engaging in in cigarette smoking absolutely ruins their sperm. But if you stop smoking and you remove yourself from that environment and you look to be healthy, then that it r it rebounds amazingly. You know, the the cycle is around two months to generate a new set of of sperm cells and and that in in fact happens. And that's why we promote good health because of that reason.

SPEAKER_01 19:06

And so taking like, you know, I've been thinking back to year sticks getting kicked in the nuts from a soccer ball or something. Yeah, yeah. Um how can we rebound from something like that? Yeah. Um, what are we talking about?

SPEAKER_00 19:17

Yeah, so yeah. So those, I mean, those kind of physical injuries, besides being credibly painful, yeah, they they do resolve usually pretty well, like most um tissues in our body. You know, one of the the things that might align to that is we, you know, we collect samples as part of our research quite often. And what we'll notice as we move into the flu season is uh a very significant decline in the number and the and the quality of of of some samples. And then later we find out that that individual's you know had a cold or had the flu. Um and that really impacts the the quality of the the the semen sample they provide. But then in two weeks later, when they provide another sample, absolutely fine.

SPEAKER_01 20:00

And so is that oxidative stress that we're talking about there or is that something else?

SPEAKER_00 20:04

So yeah, I I think again, we don't a hundred percent know that if oxidative stress is a main driver, but what we do know is that you know inflammation because of those um because of those infection infections will affect the the production of sperm and the the quality of those of that production as well.

SPEAKER_01 20:22

Just another random question for you. Yeah uh I do a fair bit of kind of hot cold therapy, saunas and ice bars and stuff. Yep. Every time I get in the ice bath, I'm always thinking, God, this cannot be good. What's the is there an impact with that? I know getting too hot can kind of be bad. Yeah. Or about too cold.

SPEAKER_00 20:40

I I think the same rules apply. Like I think anything that's outside the norms that is extended and chronic is probably not going to be good. You're right that it's very clear that overheating the testes is is is not is not good for sperm quality and sperm production. The whole reason that the anatomy exists is so that they are at around 35 degrees, around two, two degrees roughly cooler. And and the reason for that is that the processes that underpin sperm production and their maturation within the the testicles and a tissue called the epididymis, which surrounds it, requires that temperature. So if you go up and uh above that temperature, then the biology is not used to it, then they reflect negatively. Cold temperature is a little uh less of a problem because the body will buffer that's in some regards. We don't necessarily see uh a detrimental impact on sperm cells themselves until they reach around 15 degrees, which is never going to happen inside the scrotum, even in an ice bath, unless you're, you know, you're there for days. Yeah. So uh yeah, so that would be my take on it. Certainly, again, reiterating that any anything outside the norm for extended periods of time are probably not going to be the best.

SPEAKER_01 21:55

I know there was like a uh podcast that went on around a while ago that would talk. About how there's a correlation between male athletes and having daughters. And they I think they linked it towards increased exposure to heat. Yep. And it was something to do with having more daughters than boys.

SPEAKER_00 22:13

Is that and jet pilots too. There you go. There's some. So I I will say that I I don't believe there's any good scientific data that proves that, but certainly anecdotally, it seems to be quite popular. We don't know uh what that mechanism might be. Interestingly, with other animal species, there's technologies where you can actually select the X-bearing or the Y-bearing sperm, then becomes either the female or the male. And then you can select them and you can use them to create a male or a female offspring in those in those animals. However, that that technology doesn't seem to work for humans. So there's no real um good way of selecting a a male or female sperm. So it's it's difficult to understand what might be driving a selection there again. The the science behind it is uh is probably quite controversial.

SPEAKER_01 23:03

Yeah, we'll we'll jump into the biomarker field a bit later.

SPEAKER_02 23:07

Yep.

SPEAKER_01 23:08

Drinking. So we know that's if you don't notice, you should probably go and check it out. Drinking during pregnancy is extremely harmful. What about for men when you're trying to conceive?

SPEAKER_00 23:20

Yeah. Yeah, so interesting here, like I might go on a bit of a story and you might bring me back if I get too far. But yeah, we were talking about oxidative stress as as being a a key central mechanism to that that damages sperm production and sperm quality. And therefore antioxidants perhaps combating that. So interestingly, there are a lot of antioxidants in things like wine, even beer. Uh so if we if if we look beyond the the alcohol, some might argue that having moderate drinking habits, not moderate, but in moderation, um, might have some benefits. And you might, you know, you see this in the media sprinkled through every now and then drinking red beer. Which is the same thing. The antioxidants drinking red wine um might have a benefit to you. So keep that in mind, I suppose. But again, it's to do with moderation. So for a for a woman that is or a female that's um become pregnant, then uh and and really you advise them while they're trying to become pregnant, they should not be drinking alcohol at all. That very first uh couple of weeks of fetal development is absolutely crucial and very sensitive to alcohol. And that's why people get that advice. For the man, it again, or the male, it it's the same advice where you know, if you're looking to conceive with your partner, then you should be maintaining your best health as possible. I personally think that a drink here and there is not going to be bad. If you are having problems conceiving, then I would cut it out completely. Um, and that would be, you know, some advice from the GP or the facility specialist as well. So yeah, I mean, you don't want to be binge drinking while you're trying to conceive.

SPEAKER_01 25:06

What about testosterone? What's the relationship between high testosterone and sperm count, lower testosterone, sperm counts, things like that?

SPEAKER_00 25:13

Yeah. So there are pathologies where the hormone androgen production, so the male hormones such as testosterone, as you've just described, is dysregulated. So they're they're not made or circulated in the right levels. And that has drastic impacts on fertility. Um, you know, the main area of production of testosterone is within the testis, within a uh type of cell within the testis, and that uh directly informs the the change from your stem cell, sperm stem cell into the more mature stem cell. Sorry, the mature sperm cell, um, and the numbers of those as well. So any disruption to that balance uh will will affect the the production of of sperm.

SPEAKER_01 25:57

Is a disruption to the the balance that's considered normal for the individual, or is it considered normal for a standard level of testosterone?

SPEAKER_00 26:06

Yeah, the there's usually a standard level. That level of testosterone will start to wane with male age, but as I said, that's reflective of the ages that are provided before. So around that age kind of 40, it starts to decline. 45 to 50 is where it starts to markedly um decline. But that doesn't stop sperm production whole wholesale. But it's certainly that testosterone starts to decline. So yeah, so certainly, you know, if there's a problem with sperm production for a a male in their fertile window, then looking at hormones is a very important part. Um and they there may be a pathology where they're not producing enough testosterone, for example. So um, and that's another odd underlying condition. Yeah. And that can be sub sometimes can be fixed as well with supplements.

SPEAKER_01 26:50

I don't know if this is a misconception or not, but in the you know, bodybuilding, gym lifting world, it's like a it's a common thing to say you'll take testosterone and you get small nuts. Yeah. Um or if you're taking testosterone, you won't be able to have kids or something like that. Yeah. Is there some truth behind that?

SPEAKER_00 27:07

Absolutely. Again, the balance, you know, the there's a a concentration window which has been uh very finely tuned over the the course of our evolution that maintains uh you know prime reproductive potential. If you go outside those windows, then biology doesn't cope with that. And that that cuts across many different types of scenarios, not just reproductive biology, but yeah, certainly um too much testosterone will affect the the production of your sperm.

SPEAKER_01 27:34

And would you see it bounce back if you were to stop taking it? Absolutely. Yeah, absolutely. Yeah, cool. Another kind of common, I don't know if it's a misconception now, you'll be able to tell us this is phone use, Wi-Fi, 4G, you often get labelled a conspiracy theorist if you're shouting that there's dangers to using it. You've done actual research on mobile phone use and sperm health. Yeah. What did you find?

SPEAKER_00 28:01

Yeah, so this is this has been a really interesting um kind of part of my research career. Um we we we had a grant finished up, I think, in about 2019 from the NHMRC, which was to look at uh this idea. And yeah, really interesting projects. What we found was that, you know, I suppose myself being more fundamental scientists, coming from a chemistry background, but also reflecting in our laboratory at at Newcastle University, is we're really interested in fundamental discovery science. And we strongly believe that uh that understanding will lead to better healthcare in in the reproduction space. And that's generally the way we do things. So I tackled that that question from that situation. So the first thing I wanted to do is like really smash the sperm. Like I got purified the sperm, so they're just in a little petri dish, chucked them in uh what we call a waveguide, which simulates things like Wi-Fi, mobile phone signals, and really hammered them. So, you know, basically like chucking them in the microwave. We we we made sure that there was no heating effects when we did that. So we we controlled for that. And and what we found is very clear, and we repeat it over and over again. I've had a number of students and and um PhD students looking at this, and there is a dramatic effect. The loss in motility is incredibly clear. So after these exposures to things like 3G network signals, for again, quite high level, we're talking about not the levels that you would see in the environment necessarily, there are clear effects. So there are there is something going on there. So then we've taken that further and and looked to see in a more realistic way if there may be effects. And and what we've seen is that yes, there is. While we still don't know what the those kind of signals and Wi-Fi means for our reproductive health, we certainly do know that there is a biological effect, and we're honing in actually on the very granular detail of what how those effects come into come to pass. Um and yeah, very excited about, you know, hopefully getting some more funding to to look at that further. The take-home message is that we know that there is an effect, absolutely. A lot of a lot of people, you know, perhaps in the telecommunication field will will tell, will say that that's impossible, that there's there's no effect, but I hand on heart, I can can see that um quite clearly, again, over many years of replication. If there is an effect, we may not see it for you know a couple of generations. So obviously, if the effect was great, you know, none of us would be fertile anymore, right? We'd all be dropping dead from brain cancer and things like that, but that's not happening. So if there is an effect, it's gonna be much more subtle, which we might not see for a couple of generations. So again, our our message is that if there is an effect, it would be better to know sooner rather than later.

SPEAKER_02 30:55

Yeah.

SPEAKER_00 30:56

What we're hoping is that there isn't, and it's a good news story. But I think you would agree with me, and I think the public would agree with me. It would be good to know.

SPEAKER_01 31:04

Yeah, especially the preventative side of things. I think that was a lot of people's concerns not to dive into this kind of conspiracy so much. Yeah. But with the COVID vaccines, a lot of people were like, we we don't know what the long-term effects of these are. And and normally there's research that's been done years on years and on end for vaccines. And I think that was a lot of people's fear was we don't want to start ingesting things that we don't know the long-term effects of. Like maybe it won't, you know, harm us in the immediate moment, but what's it going to look like down the future? And I think that's super important. Is the answer we we walk around with without our phones in our pockets? Is it designated time away from all these signals and things?

SPEAKER_00 31:44

Um I I think you know that you know we look at certain environmental factors on their own. So we we've looked at things like Wi-Fi and and phone signals, we've looked at um, you know, now banned flame retardants, we've looked at heat stress. But I and we firmly think that it's probably a combination of all those things that might be impacting uh um uh a male's fertility. So what I say, you know, when people ask me about mobile phone devices and the use of laptops is the same I would say, you know, around smoking and around general health. Is if you're trying to conceive, then maybe it's better to keep the phone away from your front pocket. And I always make the joke that I've had my two beautiful children, so I've got my phone permanently stuck to my um, you know, to my thigh. But yeah, I mean that's that's the advice is that you know we we don't know, but there's some biology to suggest that that with other things are leading to a lower fertility. So anything that you can do to maximise your fertility in that window, why not do it?

SPEAKER_01 32:43

Yeah, and that's kind of operating on the rule of our fertility system will bounce back uh even if there is some small level of harm going on there.

SPEAKER_00 32:52

Again, uh males are somewhat lucky uh in that regard again, because that's exactly true. You know, if we have had some sort of insult, like if we've gone gone through a very um bad flu and our a fever has affected us, our our testes will warm up and the sperm production will be heavily impacted by that. Wait a month or two and it's completely back to normal. And it's the same with any other kind of external stress. Most of those that don't affect the stem cells where the where our sperm comes from, the fertility will bounce back. Yeah. Unlike in the female.

SPEAKER_01 33:25

And so kind of moving further down the line here, parental age and future child health, we know that oxidative stress plays a role. We know that radiation, things like that can play a role, heat. We kind of mentioned the example before of Robert De Niro. Yeah. How does age directly affect uh sperm?

SPEAKER_00 33:45

Yeah. So as a a man ages, the ability to, I suppose, produce sperm cells with the fidelity that a younger man or male would is less. Okay, so you're still able to produce sperm, no problem with that. But there's incredibly intricate mechanisms involved in creating that sperm. I can't remember the exact um time frames, but I think for a mouse, it takes something like uh two months to make a sperm cell. However, to make a new mouse, it takes a couple of weeks. So it takes more time and and energy to make a sperm cell than it does to make a whole new individual, right? There you go.

SPEAKER_01 34:28

On that point, before we keep going, sorry, we can digress and come back.

SPEAKER_02 34:32

Yep.

SPEAKER_01 34:32

We're looking like what's what's the world look like in 20, 30 years? We're creating AI technologies. There's people, I think it was in Norway, maybe Canada, that are bringing back the direwolf. Where's the science taking us on this? Obviously, IVF and things like that is somewhat external. What's the extent that we can create more?

SPEAKER_00 34:53

That's um, yeah, that's a that's a very interesting question. Um, I think certainly as science progresses, it will be done. Even the knowledge that we've gained around genetics, epigenetics, which means, you know, certain heritable traits that are not specifically in our DNA, other than other factors, um, the pathways that govern development. So, you know, how a fetus goes, how how a sperm and an egg gives rise to an embryo and then a fetus. I think our improvements, the advances in our knowledge has been insane over the last 20 years. Um, when I've that I've been involved. So, you know, that's only going to continue. And so, with full understanding, I think you will be able to do that.

SPEAKER_01 35:34

Yeah. Yeah, I think that was an interesting point I wanted to talk about today with the diewolf example, because we've got, you know, this species that we're supposedly bringing back. I think the study was using wolf-like species that have kind of been passed through the tree for thousands of years to kind of help that process. But the interesting question for me is we've got these prehistoric animals that are trained to hunt and do all their automatic behaviors and we're putting them in a world that's completely different now. It's probably an impossible question to answer, but how would you expect that to interact if you were to pull a completely different animal from thousands of years ago and put them into today's society and then replicate from there? Yeah, uh, what would what do you think would happen?

SPEAKER_00 36:19

So, I mean, there there's a lot I think there's a fair bit of work going on um around de-extinction. One of the the questions is like, should we be doing this? You know, is it is it appropriate to be doing this? Because, you know, what are the impacts for this animal that was around in a as you've said, Ed, you know, in a very, very different environment. What you know, is that ethical to now bring them back into this environment? What potential impacts would that have for the animal, but also the the the ecology that's uh that surrounds it? So that's a question that people are certainly asking. In in terms of the animal, uh, you know, I I have a colleague in Melbourne who's who's working on on this, um, who's funded by Colossal, which is the firm that's you know trying to bring back ultimately the woolly mammoth. He's looking at using the Tasmanian tiger. Um so bringing back the Tasmanian tiger. And the again, the technology they're developing there is uh, you know, insane, absolutely insane, because they have the um the the support to be able to do it. And they're making progress. That one of the things that we know is that we we don't have that animal to give birth to that animal, right? So they're the there's a a multitude of different biological and scientific problems that need to be overcome before that happens, but I think it will. Now, what again, what that means for the animal, uh animal's ability to reproduce, I think will be very important topic. And I I would doubt that, you know, the first iteration, if I can say it that way, of bringing back or de de-extincting these animals, I doubt that they would probably be fertile. But we we never know.

SPEAKER_01 37:55

Yeah, yeah, it's an interesting topic. Yeah, I I think the ethics behind it is yeah, it's an interesting conversation to have as well. Are we using these technologies for the purpose of saving endangered species or are we bringing them back just for the sake of creating a Jurassic Park?

SPEAKER_00 38:10

The pursuit is very is very worthwhile at the moment because you know, what it's doing is a really accelerating technology, which is fantastic. So it doesn't necessarily need to be used for de-extinction, yeah, but it could open up a whole bunch of you know, medical, for example, um a whole bunch of other avenues. So that technology, that investment to get that technology is well worth it.

SPEAKER_01 38:32

So kind of coming back to before we digress, yeah, yeah. Uh we're talking about parental age, future child health. Yeah. Is there correlations between older parental age and autism?

SPEAKER_00 38:44

Yeah. So for the female, uh fertility drops off quite precipitously, you know, around that age of 32 to 35. And then, you know, you can go from around having a 25% chance of being pregnant when you're 32 to about a 2% chance when you're 42. Right. So there's a huge decline. Um, now for the male, that doesn't necessarily happen as sharp um as that, nowhere near as sharp. But what does happen is that quality of sperm production, particularly the qu the maintenance of the paternal genome within the sperm, which ultimately is what sperm are, right? They're really, you know, just a package within a little outboard twiggly, you know, sort of tail motor to get that paternal genome to the egg. So the the fidelity in in preserving the right, that paternal genome intact is lessened as you age. So what that means is there's a potential to bring in mutations or DNA damage into the embryo. Sometimes that's not detrimental. Sometimes it's not detrimental to the next individual, but it can well be with cumulative, uh, I suppose promutations is what we say, because there's there's not a necessarily a mutation in the sperm itself. It's it becomes a mutation once fertilization takes happen, uh, takes hold. Um but after subsequent generations, if we keep using sperm that are that contain DNA damage, then it's very likely that we're going to get bad mutations in the embryo. And this we know that this can lead to um miscarriages. Um, you know, where the the embryo forms, but there's too much damage that's come from the father that leads to miscarriages. That's in a more extreme situation. But then there's much more subtle situations where this DNA damage doesn't necessarily have an effect on the viability of the offspring. So the offspring can be born normal. But then we see um these uh a very strong link with complex neurological conditions such as autism, which again makes sense because I think you know the changes that we're likely to see in the sperm have to be subtle. If they're if they're overt, then the sperm probably won't fertilize the egg or the embryo that it's supporting probably won't make it through to full term. So if it's a subtle effect, then a subtle thing like complex neurological conditions makes sense. And there's a very clear link to the the the prevalence of autism in the offspring with paternal age. So as a as a a man becomes older, the likelihood that you're going to father a child with autism uh becomes increased.

SPEAKER_01 41:24

And so is that a hypothesis for why we're getting massively increased autism rates now?

SPEAKER_00 41:30

I I don't know if it's something I could really comment on confidently. I certainly understand the the biology behind how that mechanism would work. You know, and we've got publications on that that that also uh link oxidative stress to that. However, yeah, I I suppose I would have to be more well-versed in, you know, that that common idea is is it something that we're screening for or noticing a bit more than we used to? Um so it's difficult to say from my point of view. But what what we definitely know, and I I'm convinced of the science, is that as a man ages, the risk of having uh the things like a complex neurological condition in the in the child is elevated. And that's due to the the mutations that can happen. That's due to the damage that's carried by the paternal genome that again the sperm.

SPEAKER_01 42:14

Yep. I want to kind of branch into this more ethical kind of discussion with you. Can you give us an overview of what for those of us that are early in their 20s and haven't had the conversation of kids yet? Yeah. What are biomarkers and what's the capabilities that we have? Can we flag for Alzheimer's? Can we flag for cancer? Like where are we, yeah, where are we up to in that?

SPEAKER_00 42:35

Yeah, and that's another controversial area, certainly ethically as well. And I find it kind of semi-linked to the idea of sex sorting sperm. Um you know, should we be able to select male or female? Yeah, I mean, the technology is certainly there. Um, we can you can create uh an embryo, which is what IVF is. So in vitro fertilization, where you take an egg, you take sperm, you let them fertilize um in culture, and then you uh look at and maintain the the early embryo as a result of that fertilization. And um so from that one cell, so that fertilized egg, you undergo mitosis, um, cell division, and you get that you've uh from Jeff screen out this thing. Excellent, excellent. Um, and then there's a rapid proliferation of cells, right? So you get two cells, then four, then sixteen, and it just expands. Um, so what you can do in the in the lab is you can take a sort of sort of rip out gently uh one or two of those cells from the embryo. The embryo is not necessarily going to miss those cells, um, and you can start looking at the the genome of of that individual. And the the technology is certainly there. Um you can certainly pick up um genetic based um diseases, you can pick up things like uh trisomy twenty one, which is an extra uh copy of uh the um twenty one twenty first chromosomes or down syndrome. you can pick up other uh genetic abnormalities as well. So if you have those genes, then you either will or very likely get um some of those diseases. And, you know, uh some of those could be things like um predisposition to to cancer. So having um, you know, these kind of guardians of our genome which prevent cancer from taking hold. If if something's wrong with the gene that encodes for that guardian, then that individual can be predisposed to getting cancer later in life.

SPEAKER_01 44:31

IVF assisted reproductive technologies, is IVF the best option?

SPEAKER_00 44:36

Great, great question. Yeah, I I I think professionally and personally believe that it is. So there's a number of different options available. The most common should be IVF. It certainly was the most common. However there was a new innovation um a couple of decades ago called ICSI, so intracytoplasmic sperm injection. And this is a situation where you would go from in vitro fertilization, so if I can set the scene, you take a sperm sample, you get an egg, you put them in a culture dish, you let them do their things, sperm swoop around, find the egg, fertilize, and you get the embryo, you culture the embryo, then you implant the embryo. That's IVF. Now many men that undergo that procedure, their sperm are present, but they might not be motile. They may be motile but they can't recognize the egg and if you can't recognize the egg you can't participate in fertilization. So the way to get around that was a technique to actually draw up a single sperm cell in the capillary and then physically inject it into the egg. And that um that act will induce fertilization and you and then you get the same kind of embryo development and you take that embryo implant it. Now the problem with that is that that is entirely artificial. So the person, the embryologist who's picking that sperm will look at the sperm and say, that looks like a pretty good shape. It seems to be motile, it seems healthy. But unfortunately we based on those principles we can't be certain then there's no DNA damage in that in that sperm. So what we may inadvertently be doing is picking sperm that harbor DNA damage and creating embryos from those sperm. If you go back to IVF, then um this is something that we're working on quite extensively at the moment there's strong evidence to suggest that the the mechanism or the process the sperm needs to go through to actually fuse with the egg and reach the egg and fuse with the egg will almost guarantee that that sperm's DNA is of the best quality. So that's why we would suggest that IVF is a much better technology not necessarily to become pregnant but for the health of that offspring IVF is much safer. So unfortunately um through the advent of ICSE that has is exploded in popularity and in fact is now the most common way of conceiving is through IXE. So what we try to do as scientists and reproductive biologists is campaign um to the public and to the IVF clinics as well who understand this as well is to revert back to IVF which we think is much safer for the offspring's health. Yeah.

SPEAKER_01 47:26

And so you mentioned before about sperm motility um and we spoke about the the effects of you know phone radiation on that does it directly just affect the movement but you said its ability to recognize an egg how is that related because obviously just movement and recognition is two different things.

SPEAKER_00 47:44

Completely two different things.

SPEAKER_01 47:45

Yeah.

SPEAKER_00 47:45

So the sperm has it's got an arduous job, right? It it leaves the testis, it goes through this tissue which I mentioned before the epididymis which is within the scrotum and then it goes through the vastephrens you know through viaculation into the female reproductive tract. The the the process of maturation for that sperm is continuous the whole way through that process. And it only gains the ability to gain the proper motility and the ability to to find the egg and engage with the egg after it's gone through that whole process. So even into the female reproductive tract. So what IVF does is try to replicate the the female reproductive tract in vitro right so we get that maturation happening. So those processes are are incredibly complex and we think that that is for good reason because if anything goes wrong with that then abort abort mission it won't work. Yeah and what we think is happening there is that if a cell has gone has been exposed to a sperm cell has been exposed to some sort of damaging agent, it's likely that it could have damaged the DNA which means that it disrupts the process the maturation process for it allowing allows it to bind to the egg. So it's a basically a an emergency stop if you like.

SPEAKER_01 49:00

Yeah there you go kind of coming back to the biomarkers IVF talk what are the kind of ethical considerations people should be aware of when going to check for biomarkers and things like that.

SPEAKER_00 49:11

Yeah it's a really it's a really tough one um I my opinion is that I mean the technology is there but you know I I think if there are major risks so if there are markers that are found which can lead to a major risk of um disease and the well being of the offspring some the sometimes less common could be complications in pregnancy as well and putting the the the female or the the the mother in in um in danger. I I think it's worthwhile having that conversation. Again I I I mean I can't I I I don't have a strong opinion um that it should be banned or that it should be not banned. But I think what I can say is the technology is there and it it could it's it's an important conversation for us to be having uh about that utility of it. Is that going to is that going to be helping society in the future? Perhaps it will but it's a but it's a larger larger discussion I think.

SPEAKER_01 50:15

There was a study that was done on pregnant women's anxiety levels after getting ultrasounds. Right. And it decreased because it was like obviously reassuring to them that baby was okay. Yeah.

SPEAKER_00 50:27

What's the kind of link because if we're testing for biomarkers obviously there's probably going to be some of that effect as well you're gonna be more reassured but what if they're they flag an issue that's obviously a dilemma there do you yeah do you want to inform someone if there is because is that going to stress them and cause more damage or yeah fantastic question Ed um I think I I think you're absolutely right I think you know the the stress that that would create um is certainly not going to be good for the pregnancy situation. And that bec that that's another part of the discussion you know what what's the the the benefit versus you know the the adverse outcomes um is it worth doing and uh and look you know I I I think there's a discussion that that's really required there. Yeah it's individual. But you're right you're right um you know even even going through the process of IBF is incredibly stressful right um incredibly stressful you know no one as you as you're kind of in high school and you know in your early 20s you you tend to think about well I don't know if I'm gonna be able to afford a house or um am I going to be able to do a a Europe trip this year. You you don't know. But one thing that you you don't really think about is your ability am I going to be able to have kids you just assume that you are going to so going through that whole problem is a shock. It's it's a huge mental load. So there's inherently uh problems with with that as well.

SPEAKER_01 51:54

I just wanted to flag that yeah yeah I think it's it's a it's a good point to make I think especially for people who are in school or maybe you're you know just finishing you know your degree uni or something it's like you have this tunnel vision to finish your education and then I'll be an adult and then I'll do this and then I'll do that. Yeah and you don't really think much further on that but then what people aren't realizing is not only are we living longer but also your life doesn't end when you're 30. You've still got you know for most people another 50 years what are you going to do then? Well you'll you probably want to have a family. Yeah. Most people not everyone and so yeah I think it is it's it makes sense that it's so stressful when you get to this point where you go, cool, I've missed my or I'm coming to the end of my kind of biological window and I want to have kids. Now's the chance and now I'm having issues.

SPEAKER_00 52:43

Yeah it would be stressful super stressful super stressful and I and I think that's why you know another discussion is very worthwhile is into how do we support people to have start families when they're biologically supposed to I suppose you know um again um you know one of the the quotes from my mentor John is that we can't change biology but we can change sci society.

SPEAKER_01 53:08

Yeah 100% that's a good point. So you mentioned how do we support people having children in their biological window.

SPEAKER_00 53:15

Yeah.

SPEAKER_01 53:15

Uh what are some of the societal changes we could have to support that?

SPEAKER_00 53:20

Yeah again I I think the the discussion around that will be really important. But you know stemming from what I know which is uh reproductive biology again we you know we are certainly looking at ways of extending reproductive lifespan and where we have a had a look a bit of look at that certainly in the female side of things. But I think the easier fix for now and the quicker fix for now is to not worry about changing our biology but but change and support people to have children younger. One of the things that again we're seeing linked to age is not only the incidence of infertility but consequences for the offspring. That's the concerning thing. So not just the ability to be able to have children but if you can have children, what does that mean for the health trajectory of our whole um population generations and generations into the future? So you know this could be something that's compiling and compiling. So um you know we should be looking at uh providing uh you know changing that ability uh or giving the choice to people to not pick a career and education and family but to do both um and and provide as a society we should be able to provide the means for for people to do that if we want to look into the future and maintain a healthy uh generations yeah yeah yeah especially when people are having kids later and later like um yeah and the research supports that as well where we're pushing that back further and further.

SPEAKER_01 54:46

Do you think it's because people are choosing careers over families.

SPEAKER_00 54:49

Oh absolutely I think you know the I mean society is geared you you said it yourself Ed you know you society is geared that you know you you do your education you do your education to get a job and then once you've got a job you want to build a uh build a career for um stability and you know hopefully for for this generation it's you know it's incredibly difficult to you know own your own home and and those kind of things um but that's why you work is you know is for most people to that want to have a family is to set themselves up to be able to do so. So yeah I I agree that that that's taking longer and longer and longer to be able to set yourself up um to do that which is not it is going against our biology.

SPEAKER_01 55:31

Yeah. And so should we only take care of our fertility health which is general health as we kind of uncovered before when we're trying to conceive or is it something that we should be you know actively keeping in mind for our lifespan.

SPEAKER_00 55:45

Yeah. I think I think education um around the importance of health and and how that's linked to reproduction is is key. And I think you know we try to engage with students around that year nine and and year ten as they're learning about um you know the sex education and and and what happens during puberty and and reproduction and and those kind of things. And I think getting that message out around uh reproductive health and getting uh younger people thinking about that is always going to be helpful. And that's a a major out um outcome that we want to try and push as a as a research unit as well. But I think the advice at the moment is that if you're if we focus on the male, if you're a male and you're undergoing um you know fertility issues, then it's not necessarily too late to have a look at your health status and try to make some changes to improve your health. So again coming back to the biology where again males are lucky we can generate regenerate um new sperm cells um so in a in a healthy environment we'll should generate more healthy cells. If you could give people listening three bits of advice what would you give them so if you're looking to conceive um I think that you know things but just be aware of things that you're putting into your body um so what what we want to do is certainly remove things like cigarette smoke, um uh illicit drugs um alcohol I'm a little bit on the fence you certainly do not want to be binge drinking um while you're trying to conceive um and general health uh balanced diet I mean it sounds all very boring and and generic but but they these are critically important steps that you can make to maximize your fertility and you know for anyone listening there I I I'm I'm hoping that this doesn't apply to you but if it does if you've done if you're doing everything you can you can to maximise your fertility hopefully you won't have any problems and you'll never know which is I think the best case scenario. Is it the same advice for women? Yeah so for women it's it's slightly different um I think you know that of the I think the message is maybe perhaps much more commonly understood in our society that the that the health of the woman while they're trying to conceive and while they're carrying um a a child is key, right? Most people will inherently know that um so and that is true. But I think you know the message is that that also applies to the man. You know that's something that society doesn't seem to kind of um uh kind of grasp yet but that's the message that we're trying to get out. Where can people find more of your work? Yeah so uh you can always go to the university webpage the University of Newcastle webpage and we have a a profile there. We're also affiliated with Hunter Medical Research Institute, HMRI um and we're also looking at um getting a bunch of uh kind of public events going to to kind of get this educational uh information out to people around reproductive health um I'd also like to kind of mention that uh the the group uh based at Newcastle is quite world renowned um something that certainly attracted me to to the group uh even though I'm I was a local um the the the expertise that we have in particular in sperm cell biology is again respected all all over the world and I've had the privilege of traveling um all over the world and then seeing this firsthand um which is quite humbling actually um so yeah I I think you know if we can get that message out to say that we have a a world class uh set of expertise here in our region um and you know for anyone that's listening that that might even be professionals in the field, you know, please we do have a bunch of connections um but yeah please uh you know try and contact us and um yeah reach out. Yeah perfect thank you very much for your time. Thanks Ed. Cheers. Are you natural at this or what? This is my second episode. I think you're very good. No I think you're very