Phytoestrogens derived from soy are increasingly being used by women as a treatment for the menopause, but new evidence from researchers in the UK suggests that they could also help improve the fertility of sperm in the short term. However, the researchers stressed that the long term effects of the oestrogens could in fact be to reduce fertility.
Professor Lynn Fraser from Kings College in London, speaking at the annual conference of the European Society of Human Reproduction and Embryology in Vienna, said that environmental oestrogens, such as genistein which occurs in soy or 8-prenylnaringenin (8-PN) which can be found in hops, appear to have an even greater influence on sperm fertility than naturally occurring oestrogens found in the fluid containing sperm.
Although the environmental oestrogens were normally 1,000 times less biologically potent than the natural oestrogens, Fraser said, they could be 100 times more potent in sperm, which suggests that they might operate in a different way to naturally occurring oestrogens.
Fraser and her team looked at three environmental oestrogens and one natural oestrogen and assessed how they affected the final stage of development of sperm when it acquires the ability to fertilise an egg - the stage known as capacitation. The tests were carried out in vitro on mouse sperm.
As well as genistein and 8-PN, Fraser assessed the efficacy of nonylphenol (NP), an environmental oestrogen found in industrial products such as synthetic cleaners, paints, herbicides and pesticides, and the natural oestrogen was oestradiol 17ß (E2).
The researchers found that all the oestrogens accelerated development of sperm which had not completed capacitation, enabling them to become fertile more quickly. The oestrogens were also shown to stimulate 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).
The results were different for sperm which were already capacitated, however, with the natural oestrogen having no significant effect, while all the environmental oestrogens significantly stimulated the acrosome reaction. However, 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. Because the oestrogens accelerated this acrosome reaction, they could in fact lead to a reduction in the fertility of the sperm.
"At first sight these results might suggest that oestrogens, particularly those found in the environment, could help fertility," said Fraser. "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."
Fraser said that one of the most intriguing findings 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," she said.
"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 now want to investigate the effect on sperm of a combination of environmental oestrogens. "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," said Fraser.
"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."