Prof Lynn Fraser told the annual conference of the European Society of Human Reproduction and Embryology in Vienna today (Tuesday 2 July) that environmental oestrogens appeared to have a far greater impact on a sperm's ability to function than natural oestrogens. Although the environmental oestrogens were normally 1,000 times less biologically potent than the natural oestrogens, they could be 100 times more potent in sperm. This suggested that they might operate in a different way to naturally occurring oestrogens.
Prof Fraser, who is Professor of Reproductive Biology at Kings College London, England, and a former chairman of ESHRE, investigated how three environmental oestrogens and one natural oestrogen affected the final stage of development of sperm when it acquires the ability to fertilise an egg – this stage is known as capacitation. Prof Fraser and her team studied this effect in mouse sperm in the test tube (in vitro).
The environmental oestrogens were genistein (G), found in soya and other legume vegetables, 8-prenylnaringenin (8-PN), found in hops, and nonylphenol (NP), found in industrial products such as synthetic cleaners, paints, herbicides and pesticides. The natural oestrogen was oestradiol 17ß (E2), which is present in the female vagina and in seminal plasma (the fluid containing the sperm).
In sperm, which had not completed capacitation, all the oestrogens accelerated development so that they became fertile more quickly. The oestrogens stimulated sperm motility, capacitation and the acrosome reaction (when the cap at the head of the sperm ruptures to release enzymes which enable the sperm to penetrate the barriers surrounding the egg).
In sperm which were already capacitated, the natural oestrogen had no significant effect, but all the environmental oestrogens significantly stimulated the acrosome reaction. It is important to note that successful sperm only undergo the acrosome reaction when they make contact with an egg; if they have already undergone the acrosome reaction before contact, then they cannot fertilise an egg.
Prof Fraser said: "At first sight these results might suggest that oestrogens, particularly those found in the environment, could help fertility. However, the responses we have seen could have negative effects over time. For instance, the fact that the oestrogens stimulated uncapacitated cells in an unregulated manner could mean that the sperm peak too soon, before they have found an egg to fertilise. So in natural reproduction it could be a problem, but for IVF techniques it might be a benefit. Now we need to know what actually happens in human sperm and in vivo, and whether compounds known to be in the seminal plasma might counteract the effects of the environmental oestrogens."
An intriguing finding was the difference between the natural and the environmental oestrogens when they encountered capacitated sperm. "The fact that all the compounds had similar effects on uncapacitated sperm, yet oestradiol did not elicit a response in capacitated sperm might indicate that these molecules bind to different parts of the cell," said Prof Fraser. "The fact that the environmental oestrogens, known to be much less effective than oestradiol in standard oestrogen potency tests, were much more potent than oestradiol when tested with sperm would be consistent with such a hypothesis. We must now identify the specific mechanisms involved and determine whether the same pathways are involved in responses to all these molecules."
The researchers want to investigate the effect on sperm of a combination of environmental oestrogens. Prof Fraser said: "In real life, it is quite possible that we could be exposed to more than one of these compounds, as in a beer-drinking, vegetarian painter or farmer, for example. We want to know if the responses are even greater when we use more than one of these environmental oestrogens. My suspicion is that combinations of environmental oestrogens, even in very weak amounts, would still have a significant effect.
"Other studies, using indirect tests that do not assess actual sperm function, have reported that oestrogens affect sperm. Our study is the first to provide both indirect and direct evidence that natural and environmental oestrogens significantly affect sperm fertilising ability. These findings could be important in understanding how different compounds, known to be present in our environment, might affect sperm function in humans. Given that the environmental oestrogens are very potent and that we are probably being exposed to several at the same time, it is important to know whether they might have cumulative effects."
Abstract no: 0-119 (Tuesday 11.15 hrs CET. Hall E2) URL: http://conf.eshre.com/PDF/O-119.pdf
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