Can environmental Oestrogens Affect Sperm Motility!

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Hans van der Slikke, MD, PhD: “It’s July of 2002, we’re in Vienna at the ESHRE Conference, and next to me is Professor Lynn Fraser the past President of ESHRE. Welcome, again. You presented as a biologist a very important paper of your group - the influence of estrogens in our surroundings because there are more estrogens than we realized on fertility. Could you explain where are we talking about and what kind of estrogen influences?”

Professor Lynn Fraser: “Yes, with the compounds that we tested we started out with estradiol which is a naturally occurring steroid hormone. It’s the hormone that drives the cycle in human females. So when women go through a cycle, they ovulate, and then they have a menstrual bleed the important steroid hormone is estradiol, it’s very potent. Then we looked at three so-called environmental estrogens because they are found in various elements within the environment. We looked at two that are found in plants that are called phytoestrogens. The first one we looked at is found in soya and the second one that we looked at is found in hops and, therefore, will be found in beer. Then the third one that we looked at was an industrial compound which along with other members of the same family of compounds is found widely in paints, pesticides, solvents, herbicides, and things like that.”

Hans van der Slikke, MD, PhD: “So these are the four compounds that you tested, and how did you test them?”

Professor Lynn Fraser: “We wanted to ask the question whether these compounds which in standard assays of effectiveness are very weakly estrogenic compared with estradiol so they’re not very potent but they can mimic responses to estradiol but they’re not very good at it. We wanted to see whether all of these compounds had any effect on sperm so we’re looking for quite subtle changes. We’re not looking for decreases in sperm production, just changes in sperm function which means do these compounds have any effect on the ability of sperm to fertilize.”

Hans van der Slikke, MD, PhD: “You did the research after ejaculation?”

Professor Lynn Fraser: “We were working with mouse sperm, and they aren’t actually ejaculated because there are technical problems dealing with the seminal plasma in the mouse so we get them from the storage area in the male reproductive tract where the sperm would be ejaculated from if they were ejaculated. We put them into a culture medium, which is very much like the culture medium they use in human IVF, let the sperm disperse, divide them into different sub-groups, and then treat them with different compounds. We then treat them for about thirty minutes and then we stain them with a compound that will fluoresce if you shine the right kind of light on the cell. It’s an assay that will allow us to detect changes in the sperm function showing them going from being non-fertilizing to being potentially fertilizing. The results that we got showed that all of the compounds did stimulate the sperm to appear to become fertile more quickly using a microscopical assay. But the very surprising thing was these environmental estrogens which in a estrogenic assay are very weak were about one-thousand times more potent on sperm than the estradiol so that was very surprising to us.”

Hans van der Slikke, MD, PhD: “And you looked at the capacitation and the acrosome reaction?”

Professor Lynn Fraser: “That’s right, and what these compounds did was they just seemed to stimulate the sperm. They started out being non-fertilizing and uncapacitated so capacitation just means acquiring the capacity to fertilize, it’s switching on. So it causes the sperm to switch on and when they are switched on they are potentially able to fertilize an egg but if you keep stimulating them they may undergo something called the acrosome reaction, which causes the breakdown of membranes in the anterior part of the sperm head. That means the sperm is no longer able to fertilize an egg if it comes into contact with an egg. Normally, the acrosome reaction only acquires when the sperm bumps into the egg.”

Hans van der Slikke, MD, PhD: “Before that, it has a highly estrogenic surrounding within the woman’s genital tract?”

Professor Lynn Fraser: “There is estrogen but I don’t think the concentrations of estrogen are astronomically high. It’s certainly high in follicular fluid but even there the follicle before ovulation is switching over to producing progesterone so the concentrations are not probably as high as the ones that we were looking at in our test.”

Hans van der Slikke, MD, PhD: “Not even in the estrogen peak before the LH surge?”

Professor Lynn Fraser: “They might be but the only time that the sperm would be switching on relevant to being able to fertilize an egg would probably be post-ovulation. That was the sort of time period I was thinking about but of course what you’re talking about is what is in the blood, and I’m not sure how much of that will actually be present in the fluids in the uterine tube, for example. That would be an important question to ask.” 

Hans van der Slikke, MD, PhD: “Because I think we then have to look at what the clinical implication is which is the work you do because you want to show the clinical implication. Could you comment on the clinical implications of these findings?”

Professor Lynn Fraser: “Yes, the fact that all of these compounds will stimulate the sperm and just keep going and appear to over-stimulate the sperm so that they may become non-fertilizing, if that actually is what happens in the female, then that would decrease the number of sperm that might be able to fertilize an egg when it comes around because once the sperm has gone through this reaction it can’t go back so it’s irreversible. So once a sperm has done that, yes, it’s exhausted in the sense that it can no longer fertilize. It may still be wiggling but it’s no good as potentially fertilizing sperm so if that’s what really happens in the female tract it could be bad news for fertility but there are other molecules around that might be able to sort of save that last step and prevent that. If that happened then it would be good news because the sperm that were there, ready, and waiting for the egg would be ready to go and then when they bump into the egg they would be able to fertilize.”

Hans van der Slikke, MD, PhD: “What are you plans in the future as the next step in this research?’

Professor Lynn Fraser: “We’ve worked with the mouse model because it has a number of advantages, particularly, in that although we started out doing a microscopical assay the results that we got suggested to us that the sperm would be able to fertilize more quickly. With the mouse system we can do mouse IVF very easily and we were able to demonstrate that just treating the sperm for fifteen or twenty minutes made them much more fertile than the untreated controls so we got over twice as many eggs being fertilized in a very short period of time. It was really quite striking and very significantly different so that’s actually the first demonstration that estrogens do actually stimulate fertilizing ability in mammalian sperm so that’s a very important thing to have established. But what we need to know now and one of the important questions is - what are the effects of combinations of environmental estrogen? They are a thousand times more potent than estradiol so you only need a small amount. If you’re only exposed environmentally to even lower concentrations the chances are that you and I are probably being exposed everyday to several or many of these compounds all at the same time and the real question is do you get an additive effect so a little bit of several different compounds may be enough if they’re working by the same mechanism. They actually then give you a significant effect, and I think that’s very important to establish.”

Hans van der Slikke, MD, PhD: “Where is this coming from and can I mention drinking beer and eating soya, but what about these other compounds?”

Professor Lynn Fraser: “There’s been quite a large change to our lifestyle in the last forty to fifty years and we now use all sorts of items that were never available before. All sorts of plastics - plastic containers, plastic wraps, the coatings that they put on the inside of the tins in which foods are sold, all of these solvents, paints, and we use pesticides and herbicides all the time in the garden, so we’re exposed. I think many times we’re not actually aware that we’re being exposed. There have been concerns about some of these compounds if they’re in high enough concentrations they can cause very damaging effects on reproduction. We’re looking at much more subtle effects but even so I think we really need to know whether or not the responses that we’ve seen will occur in human sperm. Now I believe that they will because we have looked at other molecules that we’re shown to have a significant effect on mouse sperm and the same molecules have essentially the same effects on human sperm so the mouse sperm model is a good place to start particularly because we can do IVF for research purposes. You just cannot do that with humans because you cannot get human eggs, it’s impossible.”

Hans van der Slikke, MD, PhD: “And then it’s only the fertilization so you cannot actually research on pregnancies.”

Professor Lynn Fraser: “You could do that, yes.”

Hans van der Slikke, MD, PhD: “In a normal clinical situation.”

Professor Lynn Fraser: “You have a proper experimental model that you can look at all the different stages and you can do that easily.”

Hans van der Slikke, MD, PhD: “I thank you very much for this interview, and I hope that you can tell us more next year in Madrid.”

Professor Lynn Fraser: “I hope so too.”

Hans van der Slikke, MD, PhD: “Thank you very much.”