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Confused fish New Scientist Jan 98

Up to 60 per cent of male fish in some British rivers have developed significant female characteristics because of chemicals in effluent that mimic the hormone oestrogen, a study commissioned by the Environment Agency suggests. Researchers from Brunel University found a direct correlation between the concentration of sewage in rivers and the severity of feminisation in male roach-including eggs in the testes.

LONDON NEW research has confirmed fears that men are becoming less fertile. The study shows a halving of sperm production in 10 years. Scientists made the discovery after post-mortem studies of mostly middle-aged men from Finland who died between 1981 and 1991. During that time the proportion of men who had the normal biological processes leading to sperm production fell from 56.4 per cent to 26.9 per cent. During the same period there was a significant increase in the number of cases of "spermatogenic arrest", or men who did not have any mature sperm cells. The incidence of complete spermatogenic arrest rose from 8 per cent to 20 per cent, and of partial spermatogenic arrest from 31.4 per cent to 48.5 per cent. The weight of the men's testicles had also diminished during the 10 years. Earlier studies had already indicated a long-term lowering of both sper,in quantity and quality. A British study last year showed that men born in the 1970s produced on average 25 per cent fewer sperm than those born in the 1950s. An annual decline of 2 per cent suggested that boys bom 60 years from now could be infertile. - PA

A variety of environmental chemicals from the pill through to industrial chemicals have been recently to both have estrogenic or other disruptive effect on male gametogenesis. Tight underwaear and sedentary lifestyles may also contribute as well as children of older mothers having boys of lower fertility because of damage to mitochondrial DNA, according to Justin St. John of the Sheffield Jessop Hospital for Women.

The following two articles illustrate how caution has given way to further anxiety about environmental estrogens.

Fresh Alarm over Threatened Sperm Beth Martin and Michael Day
New Scientist 11th Jan 1997

PRESSURE to control the pollution of drinking water by oestrogen and compounds that mimic the female sex hormone is growing following two worrying discoveries. Last week, Finnish scientists published the most convincing evidence yet that sperm production by men in industrialised countries is declining. Meanwhile, an American team has found that an oestrogen mimic that pollutes many rivers, but which was thought to be relatively benign, can render male rats infertile within two months. Previous research into declining male fertility was controversial because the results relied on sperm counts made on semen samples, which are notoriously unreliable. But researchers led by Jarkko Parjarinen of the University of Helsinki avoided 6 the problem by examining We stffl tissue from the testes, taken at postmortem from know 528 middle-aged Finnish men who died suddenly in either 1981 or 1991. Among the men who died in 1981, 56.4 per cent had normal, healthy sperm production. By 1991, however, this figure had dropped dramatically to 26.9 per cent. The average weight of the men's testes decreased over the decade, while the proportion of useless, fibrous tissue increased, says a paper from the Finnish team in the 4 January issue of the British Medical Joumal. other researchers in the field are. impressed with the study. "There has been some doubt about whether sperm counts are falling, and up tfll a couple of months ago I'd have said I wasn't sure that it was true," says Michael Joffe, a fertility expert at St Mary's Hospital in London. "But with results like this I'd say there are declines in some areas." Scientists are still some way from identifying a clear culprit, however. "We still don't don't know what's causing falling male fertility," says at's Joffe. Many believe that oestrogen from women's urine in sewage is the faffing most likely contender (This Week, 16 November 1996, p 7). But the latest research by Frederic Boockfor and Charles Blake of the University of South Carolina Medical School in Columbia sounds a fresh alarm about industrial pollution. Boockfor's team injected rats with octylphenol, an organic compound based on a benzene ring which is a breakdown product of a detergent used in the manufacture of paper, textiles and plastics. The rats were given 20 milligrams or 80 milligrams of octylphenol twice a week for one or two months. The lower dose caused an accumulation of octylphenol in the rats' tissues similar to that seen in fish from polluted rivers. "After only one month, the rats had a 50 per cent reduction in sperm count and a fourfold increase in sperm abnormalities," says Boockfor. After two months, even at the lower dose, the rats' testes had almost completely degenerated. "We didn't expect to see this complete destruction of the reproductive organs," says Boockfor. "We were a bit shocked." His and Blake's results will be published in a future issue of the joumal Biology of Reproduction.

Here is the previous position summarised.

Panic Over Sperm Counts May be Premature Norman Bauman, New York
New Scientist 11 May 1996

AMERICAN men are not suffering from declining sperm counts. In fact their sperm seem to be doing rather well, researchers announced at a meeting of the American Urological Association in Florida last week. What's more, sperm counts are closely correlated with birth rates, says Harry Fisch, director of the Male Reproductive Center at Columbia Presbyterian Medical Center, New York. Fisch's findings contradict those of European researchers, who have been amassing evidence for a worldwide decline in sperm counts. In 1992, Niels Skakkebaek of the University of Copenhagen sounded the first alarm. After analysing data from studies going back to the 1930s, he concluded that there had been a dramatic decline in sperm counts. Last year, a French study confirmed that counts were falling in Paris. Skakkebaek and others argue that the decline-together with other male reproductive problems such as an increase in testicular cancer and malformations of the penis-might be linked to rising levels of oestrogen-like compounds in the environment. People are exposed to oestrogen mimics in foods such as milk and soya beans, and through polluting chemicals such as PCBs, dioxins and detergents. Other researchers found male fish in polluted waters behaving physiologically like females, and there has been a shift in the sex ratios of alligators in polluted waters in Florida. Fisch, however, believes there has been no decline in sperm counts. He says that the European studies were flawed because they failed to take into account geographical variations and fluctuations from year to year, or suffered from sampling bias. Fisch renewed sperm counts of 1283 men who banked sperm between 1970 and 1994 before they had a vasectomy, in Los Angeles, Roseville in Minnesota, and New York City. He found a statistically significant increase in New York and Minnesota and a slight but not statistically significant increase in California. The average sperm count rose from 77 million per millilitre in 1970 to 89 million/ml in 1994, he reports in the latest issue of Fertility and Sterility. In the same issue, Alvin Paulsen of the University of Washington in Seattle, reports that he found no fall-off in sperm counts among 5 1 0 students who donated sperm for research between 1972 and 1993.

Most surprising, says Fisch, was the great variation in counts both geographically and from year to year. He believes this explains why earlier studies wrongly concluded that there has been a severe decline. Within the US, counts varied hugely according to where men live. Californian men had the lowest counts (73 million/ml). In Minnesota they were higher (101 million/ml), but New Yorkers held the record (131 million/ml). But Fisch also points out that variation from one year to the next could be greater than the variation over 25 years. For example, the variation from 1976 to 1977 is almost as large as the entire variation for all years. "So if you selected two years out of this data, you could get completely different conclusions about the long-term trend," he says. "If we looked at our data from 1984 to 1994, we would also have con cluded a decline." Fisch also found a strong correlation between the average sperm count in a particular year and the birth rate in Minnesota, suggesting that sperm counts may be an index of fertility (see Graph). These findings clearly contradict those of the Danish and French studies, Fisch says. The study that first put men on alert was Skakkebaek's huge multi-study analysis, in which he looked at the data from 61 sperm count studies in the medical literature since 1930, covering 14 947 men. He found that between 1940 and 1990, sperm counts fell by 60 per cent on average, and he concluded that there was "a genuine decline in semen quality". Fisch points out that 93 per cent of the men in Skakkebaek's pre 1970 data were from New York, where he found sperm counts were highest, whereas after 1970, most of the data came from developing countries, where sperm counts were lower. He observed differences in geography, not time, says Fisch. Skakkebaek admits that a meta analysis of the world's literature is "very crude". "Fisch's data are very important," he says. Recent studies in Edinburgh and Belgium show declines, while studies in Toulouse, France, and from Finland do not, he says. But that does not mean that all is well, Skakkebaek says. 'I confidently believe there is a problem with male reproductive health." The incidence of testicular cancer is increasing every year, and in huge Denmark now affects 1 per cent of young men. He points out that Fisch's geographical variation "in itself would indicate that there could be environmental impact". "Ifs difficult to explain the difference between East coast and West coast on ethnic grounds," he says the French study, similar to Fisch's, is by Pierre Jouannet of the Centre for the Study of Human Eggs and Sperm in Paris. He studied 1351 sperm donors in Paris. Men who donated sperm for artificial insemination in 1973, at an average age of 32, had a mean sperm count of 89 million/ml, while men who donated sperm in 1992 at an average age of 36 had a count of 60 million/ml, a drop of 33 per cent. Jouannet stresses that his conclusions cannot be extended to any other place of even to the whole of Paris. "One of the most puzzling points is the tremendous variability of reported sperm characteristics from one place to another," says Jouannet. We cannot rule out the effects of chemicals in the environment. "The debate is still open."

WHERE HAVE ALL THE BOYS GONE? The mysterious decline in male births Sci Am Jul 98 13

Despite their macho swagger, males are the more fragile sex of the human species. Male fetuses are less likely than females to come to term: although 125 males are conceived for every 100 females, only about 105 boys are born for every 100 girls. In the first half of this century, improvements in prenatal care reduced the number of miscarriages and stillbirths and hence increased the proportion of baby boys in most industrial countries. But since 1970 the trend has reversed: in the U.S., Canada and several European countries, the percentage of male births has slowly and mysteriously declined. So far the decrease has not been alarmingly large. In the U.S. in 1970, 51.3 percent of all newborns were boys; by 1990, this figure had slipped to 51.2 percent. But in Canada the decline has been more than twice as great, and similar long-term drops have been reported in the Netherlands and Scandinavia. The U.S. and Canadian data were compiled by Bruce B. Allan, an obstetrician-gynecologist at Foothills Hospital in Calgary, Alberta. Allan claims the widespread nature of the decline suggests that it is more than a statistical fluctuation. "We can't deny that the percentage of boys is failing," Allan says. "But the question is, Why?" Demographic factors may be playing a role. Different races have slightly different birth ratios: blacks tend to have fewer boys than whites, whereas Asians have fewer girls. (These differences have been observed worldwide.) The parents' ages may also influence the gender of their offspring; studies have shown that older fathers sire fewer sons than young dads. But Allan found that demographic changes in the Canadian population between 1970 and 1990 could not account for the decline in the percentage of baby boys there. Some researchers believe pollution may be the culprit. A recent article in the journal of the American Medical Association notes that high exposures to certain pesticides may disrupt a father's ability to produce sperm cells with Y chromosomes-the gametes that beget boys. Other toxins may interfere with prenatal development, causing a disproportionate number of miscarriages among the frailer male embryos. (Xy embryos require hormonal stimulation to produce masculine genitalia, which may make the unborn males more vulnerable to hazardous chemicals.) Perhaps the most striking example of a lopsided birth ratio occurred in Seveso, Italy, where a chemical plant explosion in 1976 released a cloud of dioxin into the atmosphere. of the 74 children born to the most highly exposed adults from 1977 to 1984, only 3S percent were boys. And the nine sets of parents with the highest levels of dioxin in their blood had no boys at all.

Devra Lee Davis, a program director at the World Resources Institute and one of the authors of the JAMA article, argues that the declining male birth ratio should be viewed as a "sentinel health event"-a possible indicator of environmental hazards that are difficult to detect by other means. But other researchers say the link between pollution and birth ratios is not so clear. Fiona Williams, an epidemiologist at the University of Dundee in Scotland, found no correlation between birth ratios and levels of air pollution in 24 Scottish localities. Although very high levels of certain pollutants may reduce the percentage of baby boys, she concludes, one cannot assume that lower exposures will have a similar effect. To solve the mystery of the missing boys, scientists are calling for inore detailed regional analyses of birth ratios. In Canada the falloff has been greatest in the Atlantic provinces; in the U.S. it has been most pronounced in the Midwest, the Southeast and the Pacific states. One provocative theory is that the decline in the male birth ratio has been caused by a continentwide dip in the frequency of sex. When couples have sex more often, fertilization is more likely to occur early in the menstrual cycle, which apparently increases the odds of male conception. Some observers believe this conjecture explains why the percentage of baby boys has usually increased after major wars. -Mark Alpert

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