HL: You're listening to a podcast from the Medical Research Council with Hazel Lambert. I'm in the café at the Human Reproductive Sciences Unit in Edinburgh and scientists here work on research challenges involving sex hormones, fertility or lack of it and diseases of the reproductive tract every day. Recently Dr Michelle Welsh's work looking at development of male foetuses has produced surprising results that could help explain the origin or reproductive problems later in life. Now this work has been done on rats but Dr Welsh, what's the relevance for humans? MW: We used rats to investigate the normal development of the male reproductive system during foetal life and how it can go wrong. Because this work requires investigation of foetal life it's obviously impossible to do in humans. We have discovered the critical time window in foetal life when the hormone testosterone must act for the normal development of the reproductive system. Now this finding could help us to explain the origin of some of the common disorders of the reproductive system.
HL: Tell me about how you did that? How did your experiments work?
MW : So the rats while they were pregnant they were exposed to either androgens or anti-androgens that would block the effect of the normal hormone.
HL: And what's an androgen? MW: Androgens are a type of male hormone. So things like testosterone that we hear for example body builders using, testosterone is the hormone that is vital to make the male reproductive system develop normally.
HL: What's the link between androgens and foetal development? What's so crucial? MW: We know that androgens must act during the foetal window that we've identified in order to make the male system develop normally. If this doesn't happen normally it can result in these common disorders. HL: What kind of problems are we talking about here?
MW: The sort of problems we're talking about are unfortunately relatively common in newborn baby boys, such as the failure of the testes to descend into the scrotum, now that's known as cryptorchidism and that occurs in somewhere between 2 and 9% of boys at one year old. As well as that there's another disorder known as hyperspadius, now this abnormal penis development whereby the urinary tract opens instead of at the tip of the penis, it opens somewhere along the under surface. However, one of the interesting findings that we've discovered from this work is that we've actually highlighted a new measurement which can be used to represent this androgen action during foetal life. Now this measurement is looking at the distance between the base of the penis and the anus and it's termed as anogenital distance. We've shown that this anogenital distance is set up only during this foetal programming window. HL: Ok, so the distance between the base of the penis and the anus, the anogenital distance, that matches with this early time window in development. What does this mean? Does this mean that if you've got a longer anogenital distance you're going to be more fertile or if you've got a shorter one you're going to have reproductive problems? MW: Well I'd obviously like to point out that we haven't actually done any of the studies on humans yet and everything that we've been talking about today we've been extrapolating from our animal model. However it would be suggested that if the anogenital distance was shorter in the male, then that male's perhaps more at risk of reproductive problems. Now we certainly wouldn't say that they are definitely going to get cancer or definitely going to be infertile. What it might help to do is identify patients that may be at future risk. Now anogenital distance is established in the foetus but that ration remains constant throughout life, therefore it's not just in the baby boy that it could be measured, but it could actually be measured at any time throughout life. Because this isn't routinely done in humans, we actually don't have a normal standard to measure anything against. So one of the first studies that would need to be done to see if this was relevant in humans would be to measure the normal.
HL: And how do you think that doctors or nurses could use this anogenital difference?
MW: As scientists, for us our role is to help to understand how normal development happens and how it can go wrong and provide that information to clinicians and it's then up to them how they could implement it, whether it be as an early warning tool to identify patients at risk or to be used as a tool to help understand what's happened in the patient's previous history. HL: So it sounds like it's a really useful research tool that you've discovered alongside this early male programming window, is that what you were expecting when you started out on your research? Because it was experiments you were doing towards your PhD wasn't it? MW: It definitely wasn't what we were expecting. During my PhD as many scientists will appreciate, you carry along with your experiments and sometimes they feel like they're just not working, they're not giving you the answers you expected and then suddenly it all started to make sense and fitted together when we discovered this early programming window and we discovered that everything that we were actually seeing was because of this early window, whereas in actual fact we expected hormone action to be much more important later on in pregnancy. And that highlights how important it is for us to provide support and nutritional advice and care for the early stage of pregnancy for mums.
HL: So it's hormones acting early that determine how healthy the reproductive tract's going to be in later life? MW: Absolutely, yes.
HL: Hazel Lambert MW: Dr Michelle Welsh
