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Soy isoflavone may damage fertility, finds new research

6/22/2005 - The soy component genistein, one of the isoflavones seeing
increasing sales in the health food market, could damage human sperm, a UK
researcher will reveal today, writes Dominique Patton.

Genistein, and other isoflavones in soy, are marketed as dietary oestrogens to
women as a natural alternative to hormone replacement therapy (HRT). They are
also being investigated for their potential to slow prostate and breast cancer.

But Lynn Fraser, professor of reproductive biology at King's College London,
will present evidence today that even tiny doses of the natural compound can
cause human sperm to ‘burn out’ and lose fertility.

Speaking ahead of the annual European Society of Human Reproduction and
Embryology conference, Fraser said: "Human sperm proved to be even more
responsive than mouse sperm to genistein."

“These compounds are classified as environmental oestrogens, but they are very
weak, so normally you would expect them to have to be in concentrations around
1,000 times stronger to get a response similar to that prompted by the naturally
occurring oestrogen, oestradiol. Yet human sperm are responding to very low
concentrations – well within the amounts that have been measured in people's
blood.”

Moreover, when the compound is combined with other environmental oestrogens,
such as 8-prenylnaringenin (found in hops), and nonylphenol that is found in
industrial products like paints, pesticides and cleaning products, the damage to
fertility could be even more serious.

"Humans are likely to be exposed to more than one such compound at any given
time and ... our results show that human sperm are even more sensitive to these
compounds than mouse sperm."

Fraser’s team investigated the effect these chemicals had on capacitation, the
stage when a sperm acquires the ability to fertilise an egg. They found that
combinations of small quantities of these three chemicals stimulated sperm far
more than when used individually.

In particular, the chemicals stimulated the sperm to undergo an acrosome
reaction - when the cap on the head of the sperm ruptures and releases enzymes
that enable the sperm to penetrate the coverings of the egg. If the acrosome
reaction happens before a sperm reaches the egg, then fertilisation is unable to
take place because the sperm has lost special 'docking' molecules that allow it
to bind to the egg.

The study follows new research reported on Monday suggesting that infertility is
set to double in Europe over the next decade. One in seven couples now has
trouble conceiving naturally, but this could rise to one in three, said
Professor Bill Ledger from Sheffield University. An increase in obesity and
sexually transmitted disease is expected to reduce fertility.

"Very little is currently known about the control of sperm function, especially
in the body rather than in the laboratory, but the sensitivity of human sperm to
these chemicals means that further investigations should be carried out to
determine whether such environmental compounds might contribute to a decrease in
human fertility," said Fraser.

"Other scientists have investigated the negative impact of environmental
chemicals on testis function, resulting in reduced numbers of sperm being
produced, but these effects require much larger doses than we have used."

"As far as I am aware, we are the only group looking at subtle effects that
could have a serious impact on fertility without reducing the number of sperm
being produced," she added.

Fraser's team has not worked out the mechanism of action of the environmental
oestrogens but they discovered that both genistein and nonylphenol significantly
stimulated the production of cyclic AMP – a chemical messenger, produced within
the cell after external compounds have acted on the cell, that prompts an
appropriate response.

In the case of sperm, increased cAMP production appeared to stimulate premature
sperm capacitation.

"The sperm were still alive and their ability to move was unaffected, but the
spontaneous acrosome reaction meant that they were unable to fertilise an egg,"
said Professor Fraser.

She said that the chemicals were more likely to affect sperm when they reached
the female tract where they would be preparing to fertilise eggs. Maternal
exposure to the compounds is therefore probably more important than paternal
exposure.

Animal studies on genistein have previously raised other concerns. Last year a
study on newborn piglets, using amounts similar to those found in infant
formula, found that it inhibited intestinal cell growth.

And in 2003, research on rats showed that males whose mothers were fed genistein
did not achieve full sexual development as adults.

However Asian populations have long consumed soya-rich diets without signs of
reduced fertility or other health problems being traced back to the plant.

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