Background Information

Studying patterns of various health outcomes in populations can reveal significant changes in the environment and in the level of environmental toxins to which an individual is exposed. For instance, lung cancer increases in the 1950s are now understood to have signaled the growing importance of understanding the detrimental health effects of tobacco smoking. Patterns of childhood leukemia in the 1960s reflected, in part, atomic bomb testing and the use of prenatal obstetrical x-rays. More recently, the use of hormone replacement therapy has been associated with increases in breast cancer and other health problems.

So It Begins – Before and During Pregnancy

While each of us is born alone, our health can reflect the things that happen to our mothers and father before we were conceived, as well as during early pregnancy. Our new work shows that the sex of children at birth can be influenced by a number of avoidable environmental factors. It has long been known that men who are alcoholics or use certain legal or illegal drugs tend to father more female babies. Recent research has shown that people who live in heavily polluted zones and men who work in jobs with heavy exposures to pesticides, or heavy metals, also tend to produce fewer baby boys.

The Sex Ratio’s Downward Spiral?

Whether declines in births of baby boys are connected with a number of puzzling patterns in male reproductive health is a matter of serious concern. Several studies—some from the 1980s, early 1990s, and our new paper –show that over the past two to three decades the births of baby boys have declined in Japan, the U.S., England and Wales. Since 1970, the proportion of white boys born in the U.S. and Japan has dropped from 105.5 boys per 100 girls to 104.6 and from 106.3 to 104.97, respectively. Even such tiny drops in the sex ratio can amount to thousands of missing baby boys. For example, if the sex ratio in the U.S. and Japan had remained at its 1970 rate, almost 137,000 and 125,000, respectively, of the baby girls born between 1970 and 2000 would have been boys. No one knows why this is happening, but some interesting clues exist.  Since 1970, the proportion of white boys born in the U.S. and Japan has dropped from 105.5 boys per 100 girls to 104.6 and from 106.3 to 104.97, respectively. Even such tiny drops in the sex ratio can amount to thousands of missing baby boys. For example, if the sex ratio in the U.S. and Japan had remained at its 1970 rate, almost 137,000 and 125,000, respectively, of the baby girls born between 1970 and 2000 would have been boys. No one knows why this is happening, but some interesting clues exist.

When it comes to understanding what could lie behind these drops in births of white baby boys, there are compelling biological reasons for believing that whatever factors are altering the appearance or phenotypic expression of sex at birth could also be tied with a number of other increasing defects in male reproductive health, including lower sperm count, and increased testosterone and rates of testicular cancer. The biology on this point is clear; processes that take place early in pregnancy can affect whether a pregnancy will end, as well as the capacity of any baby to become a healthy young adult who can reproduce when and if he chooses to do so. Unfortunately, the topic has not been accorded the sort of funding that it merits.*

* Excerpts adapted from Devra Davis, When Smoke Ran Like Water – Basic Books 2002

Why should we be concerned about the findings you have described?

We don’t know why, over the past three decades, fewer baby boys are being born every year in the U.S. and Japan, or why similar patterns have occurred in Canada and some regions of many industrial nations. We think it’s not likely that this drop in male births can be attributed to individuals having children at a later age or that they’re using more drugs or alcohol. While there is no reason for alarm, when something changes in a similar way in a number of different countries, it is important to figure out whether there are controllable factors involved. This proved to be the case with lung cancer and smoking, with hormone replacement therapy and breast cancer. We definitely need to find out what sorts of things could account for these trends in the U.S. and Japan.

The British Medical Journal recently asked if men were in danger of extinction. They note that men die more often and sooner from all 15 leading causes of death than do women. Some trendy magazines even suggested that male health is becoming an oxymoron.

In 1999, my colleagues and I published a finding on the decline in male births in the U.S. and Canada from 1970 to 1990 in the Journal of the American Medical Association. We had no idea that the trends had continued.

Our new paper shows that the decline in the birth of baby boys has continued in the 1990s. While the percentage drop is very small, (0.022 per 1,000 births over the last 30 years in the U.S.), this translates into huge numbers in the U.S. and Japan. Currently, there are about 4 million births per year in the U.S., so this small number is significant and of public health importance.

In addition to that data, during the same period that male births have been declining in Japan, the proportion of males to females among fetuses that die before birth has been rapidly rising. Today, two out of every three Japanese babies that are stillborn are male, although no one has been able to explain why. Could it be that changes in the ratio of boys to girls born in Seveso, Grenada, Minnesota and Minimata are the warning signs of a syndrome affecting the overall pattern of sex ratio at birth? Whatever the causes, it is extremely unlikely that such parallel trends would arise in so many different countries just by chance. The very breadth of the effect points to an environmental cause. Could this widespread decline in male births stem from undetected shifts in exposures to environmental toxicants or other environmental factors? Still, other researchers maintain that the widespread drop in male births is simply part of the natural rise and fall of the balance of the sexes and is not cause for concern at all. But the recent data from Japan and the U.S. show longstanding continuing declines.

What environmental impacts on mothers and fathers would you consider to be the cause of these results?

While the role of mothers is obvious, the impacts that affect the fathers are certainly going to be more important here because the fertilizing sperm determines the sex of an embryo. We know that reproductive health in males in this day seems to be problematic. Young men have more testicular cancer, lower sperm counts, and lower testosterone levels, and baby boys are being born with undescended testes and defects of the penis. So we have to start to look more closely at whether some common causes may lay behind a number of growing male reproductive health problems.

Why are boys, as opposed to girls, more severely affected by these environmental factors?

The sex of a baby is determined by the sperm. If sperm shape, strength, speed, or structure is damaged prior to the fertilization of the egg, this can throw off-kilter the exquisitely sensitive chain of events that lead to normal reproduction and development.

The difference between a male and female all comes down to a Y chromosome. Males with their XY “sex gene,” as opposed to females with their XX, lack the extra leg on which to stand. The Y chromosome appears to convey some sort of genetic vulnerability that the X does not have. Many diseases disproportionately affect males throughout life. A number of studies have indicated that male embryos are more vulnerable to pollutants and disease. Workplace studies indicate that men who've been exposed to certain pesticides, mercury or solvents, father significantly fewer baby boys. Other modern chemicals that mimic estrogen or disrupt hormones may also be involved. In the small Japanese city of Minamata, for example, heavy mercury pollution during the 1950s caused neurological damage in many residents and severe birth defects and mental retardation in babies exposed in the womb. More boys than girls were born with Fetal Minamata Disease (FMD), as these birth defects came to be called. In the times and areas of heaviest exposure, fewer boys were born at all. The reason may be that males are more susceptible than females to damage from contaminants like mercury. When exposures were heaviest, the males that would have been born with FMD were so severely affected that they did not survive to birth. Studies of children exposed to lead have found that boys suffer greater IQ deficits than girls exposed to the same levels. Provocative studies have also linked lead exposures to criminality and reduced fertility in males. In all mammals, slightly more males are born than females. The ratio in humans is normally about 1.06:1, about 106 boys for every 100 girls. To maintain a balance between the sexes, it appears that we need to start out with more males to make up for losing more of them throughout life.

Changes in the ratios between female to male babies could reflect changes in the ratio of X:Y sperm but are more likely to reflect increased lethal mutations in XY fetus.

1. Changes in the X:Y sperm ratios. Studies have demonstrated that exposure to persistent organochlorine pollutants and changes in the Y:X sperm ratio (Tiido, et al 2003, Human Reprod. 2005). Changes in the sperm ratios during the process of spermatogenesis is unlikely since genes encoded on the tightly packed DNA and specifically the Y chromosome are not likely involved in the sperm maturation from the secondary spermatocytes to the mature spermatids. Spermatids are capable of surviving and fertilizing an egg even in the presence of Y chromosome mutations or in the absence of the Y chromosome, suggesting that lethal mutations on the Y chromosome may be involved in reducing the sex ratio at birth.
2. Review in (KEN McELREAVEY and LLUIS QUINTANA-MURCI, APMIS, 2003) Studies have demonstrated increased frequency of testicular dysgenesis syndrome, which is potentially attributed to in-utero exposure to environmental pollutants and results in mutations in the fragile Y chromosome. This involves a decline in human male reproductive health, which includes a high incidence of cryptorchidism and hypospadias, low semen quality and lower testosterone levels, and an increasing incidence of testicular cancer. Studies find that the genetic background of the Y chromosome can influence the frequency of testicular dysgenesis. While the presence of the somatic mutations in an infant could result in reduced sperm quality or even testicular cancer, it is possible that sperm with Y chromosome mutations can not be tolerated during embryogenesis. This is supported by the high number of male fetal deaths among the same population that result in an increase in the female newborn over the male.
3. Other possibilities could also include the potential lethal combination of androgen activation and environmental toxins.

Isn’t it true that men are facing other reproductive health problems aside from these issues you have described?

Yes. Testicular cancer rates have grown about 50% in most industrial countries, according to the World Health Organization. The Spanish province of Grenada, consists of 4 % of the nation’s land area, and used about 60% of all the country’s pesticides. Boys born in Grenada had significantly higher rates of undescended testes that required surgical correction.   In Western Minnesota, areas with the highest rates of pesticide spraying had the highest rates of birth defects in males, with rates peaking nine months after peak spraying time. In Sarnia, Canada in Ontario, and in Falkirk Scotland, very low proportions of baby boys have been found in areas with heavy industrial pollution.

Taking this all into consideration, what is the big picture?

All of this is part of a complicated puzzle, but could be part of a larger syndrome of male reproductive health. The same things that are increasing testicular cancer, lowering sperm count and testosterone, could also be involved in reducing the odds that baby boys will be conceived and born. 

What are some of the sources of these environmental toxins?

One is a persistent chlorinated pesticide called dibromochloropropane (DBCP). In the 1970s and more recently, men who worked to produce it fathered significantly fewer baby boys, and some of them became sterile. In the 1950s, lab experiments showed that this compound shrank the testes of male rats. In Minimata, Japan, men with the highest exposures to mercury from the water and fish, fathered significantly fewer boys. In Italy, an explosion of a chemical plant scattered traces of dioxin throughout the small mountain community of Seveso in 1976. Within a decade, a dismaying impact of the Seveso explosion became evident. Men who were young at the time of the explosion have fathered far fewer boy babies, even when married to women from outside the affected areas. Between April 1977 and December 1984 (the period corresponding to dioxin’s half-life, or the amount of time it takes for half of the body’s dioxin to be naturally eliminated) 74 children were born to parents in the zone of greatest exposure. Of these, 48 were female and 26 male. The stored serum samples taken from the exposed populations in 1976 were analyzed using a new technology in 1984. Not a single baby boy was born to the nine couples with dioxin levels above 100 parts per trillion.

Are mercury and plastics causes for concern, as well?

Mercury, in the United States, comes primarily from seafood. Fish and other varieties of seafood are exposed to mercury from a combination of industrial uses and power plants, which emit mercury when they burn coal. So, burning coal is a problem.

Not all plastics are bad, though some of the wrappings for meats and cheeses are made with polyvinyl chloride, which can be released into the food.

Couldn’t increased psychological stress be the cause of the sex ratio changing?

Stress can do a lot of things, but it's unlikely that with populations of over 400 million people you're going to get stress alone explaining these things. One of the most important clues to all of this comes from research in Sarnia, Ontario, Canada, where a community complained about the lack of boys being born.  A collaborative PAR process between the Occupational Health Clinics for Ontario Workers (OHCOW) and the Aamjiwnaang Environment Committee carried out a study and found that this community had the lowest rate of baby boys ever found in the modern world. Unfortunately, it was the classic problem of public health research. The town is a mixture of all different sorts of pollutants, including asbestos and other air pollutants, solvents, and dusts. There seem to be too many factors involved to pinpoint the cause. But at least we've created a framework for which to ask the question.

Why is the sex ratio for African-Americans holding more steadily as the whites’ declines?

The short answer is: we don't know. But the fact is, there are proportionally fewer black boys born than white boys in the first place. And the fetal death rate of males, in the year 2000, was more than twice what it was for whites--so perhaps that's accounting for some of this. There are also higher testosterone levels in black women than in white women, and black men do not get testicular cancer at the same rate that white males do. So if we conclude that whatever is causing the rise in testicular cancer is also associated with lower birth rates, you could make the argument that it may not apply to blacks. But at this point, we really don't know.

Are the sex ratios in countries other than Japan and the U.S. following this downward trend?

Absolutely. This same pattern has been shown in England and Wales, Bolivia, Denmark and the Netherlands, and a number of other countries. The thing is, it's not always easy to collect this sort of information, which is why we focused on countries with advanced methods of record-keeping, the U.S. and Japan. 

In addition, the polar bears of the Arctic, and frogs of the Nebraska corn fields are showing up as hermaphrodites, with male and female sexual parts. We've got to figure out what lies behind these puzzling patterns.

Tiny amounts of fumes, gases and alcohols hardly seem like strong enough factors to affect a man’s ability to reproduce. 

Fat has been called a natural hazardous waste site, because it attracts chlorinated organic materials, whether they are sloshed onto the skin or inhaled into the lung. One of the fattiest remnants of the human body is seminal fluid, which packages sperm and provides a ready vehicle for continued exposure even after pregnancy has begun. For years, scientific warnings were dismissed that demonstrated that male cigarette smokers and men who snorted cocaine fathered babies that were more sick than usual. Within the past few years, many studies have found residues of these agents in seminal fluid. Indeed, some of the byproducts of cigarette smoke are identical to those found in the industrial workplace and local environment.

What other areas have presented such unusual patterns?

Professor Andrew Watterson of Scotland’s Stirling University reports that for Scotland overall sex ratio has not declined, but within one highly industrialized region of Forth Valley, in Falkirk, some of the lowest sex ratio of births occurred in the most polluted zones in the past twenty years.  In another heavily industrialized area of Sarnia, Ontario, exceptionally high mercury levels were discovered in the sediment, and the sex ratio there is also among the lowest ever found.  Although the numbers observed in these instances are small, they are consistent with other findings, such as the overwhelming data in Minimata, that indicate that changes in sex ratio can signal important environmental factors.

What about smoking, alcohol drinking, or obesity? Couldn’t they account for these trends?

As to the reported observation that smokers have reduced sex ratio in their children, insofar as smoking rates have DECLINED recently in all industrial countries, this seems a highly unlikely explanation of our findings. As to obesity or drinking, or other such behavioral changes, there is not likely to be one simple explanation for something as exquisitely sensitive as sex ratio.  These factors need to be considered along with the increased use of hormone mimicking compounds.  Alcohol and obesity both increase estrogens.  Obesity results from excess nutrition and inadequate activity, but also can be affected by eating foods or drinking alcohol that contains hormonally active compounds.

For further information, these scientists may be contacted:

Nik Vanlarebeke: nicolas.vanlarebeke@ugent.be
Business: 00132. (0) 2.380.14.10

Annie Sasco: annie.sasco@isped.u-bordeaux2.fr
Business:  0033 5 57 57 45 12

Lovell Jones: EXGYN@aol.com
Business: (713) 563-2764

James Brophy: jbrophy@ohcow.on.ca
Business: (302) 831-0795

Andrew Watterson: a.e.watterson@stir.ac.uk

Shanna Swan: shanna_swan@urmc.rochester.edu