Zeroing In On Male Infertility

Researchers have found the first direct evidence that chemicals in the environment - including some in foods such as peas and beer - mimic the effect of the female sex hormone estrogen on the ability of sperm to fertilize eggs.

Scientists reported Tuesday at Europe's annual human reproduction conference that such chemicals seem to have a much more potent effect on sperm than estrogen found in the body, and that they might make sperm burn out before reaching the egg.

The study was conducted with mice, but experts say human sperm behave very similarly.

Studies have shown that estrogen-like chemicals can disrupt the development of the male reproductive system and reduce the production of sperm, but this is the first time scientists have shown they affect sperm itself. Whether the effect is strong enough to cause harm is uncertain.

Sperm expert Christopher Barratt, a professor of reproductive medicine at Birmingham University, said human sperm is even more sensitive to female sex hormones than mouse sperm.

"If the effect is true, it means you would need only extremely low levels in humans to affect sperm," said Barratt, who was not connected with the research.

Lynn Fraser, a professor of reproductive biology at King's College in London, tested the effects on sperm of three pseudoestrogen chemicals and compared the results with the action of natural estrogen found in the vagina.

The three environmental chemicals were genistein, found in soya, peas and other legume vegetables; 8-prenylnaringenin, found in beer, and nonylphenol, which is in products such as household cleaners, paint and pesticides.

The environmental estrogens had a bigger impact on the sperm's ability to function than the natural estrogen. Although the environmental estrogens were 1,000 times less biologically potent than their natural counterpart, they could be 100 times more potent in sperm.

"At first sight these results suggest that estrogens, particularly those found in the environment, could help fertility. However, the responses we have seen could have negative effects over time," Fraser told the European Society of Human Reproduction and Embryology meeting in Vienna.

"It is the first demonstration that these compounds have a direct effect on sperm fertility. No one has ever done that before. It means we need to look more carefully to see if ultimately this is a good or bad thing," Fraser said.

Sperm goes through lots of changes between leaving the male and arriving at the egg. If it fails at any of those steps, it won't make it.

The final phase of sperm development, where its ability to fertilize is "switched on," is called capacitation.

The process starts inside the female body, once the sperm has left the semen and started its journey to the womb through the cervical mucous. On average, it takes five hours to complete the process.

Capacitation involves a specific pattern of hyperactive wiggling. The outer layer of the sperm is also remodeled and the tail becomes more flexible, giving the sperm about 10 times more energy to help it propel itself.

Once the sperm reaches the uterus, it wiggles into the fallopiantube and makes its way to the oviduct, where it finally becomes quiet and stays for a day or two until it is summoned by the ovary. By this point, capacitation is complete.

In response to a signal from the ovary, the capacitated sperm travels farther up the tube to a location called the ampulla, where the egg is.

The sperm then docks onto a rubbery coat protecting the egg.

The docking triggers a cascade of events that end with the gradual rupturing of the cap over the head of the sperm, called the acrosome, which contains the enzymes it needs to penetrate the layer. The sperm then docks with the egg's shell and the tail stops swishing. The egg does the rest of the work from there.

Estrogen stimulates this process, but is not crucial to it.

The new research found that both the natural and the pseudo estrogens accelerated the capacitation process and rupturing of the sperm cap, but that the environmental chemicals did it much more quickly.

"All of these compounds stimulate, but if they keep on stimulating, at least some of the sperm will undergo an acrosome reaction (cap rupturing). Strategically, that's really not a good thing because once the sperm have undergone that reaction they can't fertilize, however much they can wiggle," Fraser said.

The important question is whether this harms fertility in real life.

"If the sperm capacitate and then acrosome react before an egg comes into view, they would be non-fertilizing, so the potential answer to that question would be yes," she said.

However, sperm are exposed to scores of substances on their way through the female tract, some of which encourage the transformation, others of which hold it back.

"If they are all interacting with the sperm, which lot is going to win out? If the environmental estrogens overcome the regulatory effects of those others, it would be bad news," Fraser said.

"Anything that affects sperm is going to have an effect on fertility."

About one in six couples worldwide experience an infertility problem. About 40 percent of cases are linked to men and 40 percent to women. The remainder are due to a joint problem.

Many of the world's top fertility experts are attending the four-day ESHRE meeting which highlights the latest advancements and techniques in reproductive medicine.