Chemical Exposures and Infertility

Warren Foster, Ph.D., and Elaine Moore, R.N.B.A.

Fall 2008

 

The prevalence of human infertility is thought by many to be increasing. There is also a perception held by many Canadians that their health has been adversely affected by exposure to environmental contaminants. However, the impact of exposure to environmental contaminants on the reproductive capacity of Canadians is poorly understood. Moreover, while there is a general perception that the prevalence of infertility has increased in recent years, several studies conducted in the United States and Canada have been unable to show an increase in infertility rates. Although the literature does not support the conclusion that infertility rates are increasing across the overall population, this does not mean that environmental contaminants are not involved as underlying causal factors in the infertility of some couples. We do know that both naturally occurring chemicals and chemical contaminants present in our environment can disrupt reproductive function in wildlife and experimental animals. However, applying generalized results obtained from animal studies to humans is difficult, and reports in the media are often sensationalized and misleading. Furthermore, it is difficult to obtain access to credible, unbiased and authoritative information. The objective of this article is to provide a brief overview of the extensive information pertaining to the association between exposure to environmental chemicals including dietary factors and impaired human fertility.

 

First, it must be appreciated that chemicals are part of our everyday life. All living organisms are composed of chemicals and indeed, life itself is the consequence of many highly regulated and complex chemical interactions. Moreover, we are exposed daily to vast numbers of chemicals through food, air and water, most of which are essential to our existence. Some chemical exposures are wanted or even needed as in the case of chemicals that make up our food and medications. For the most part, these chemicals are regarded as safe or, as in the case of medications, it is considered that their benefits exceed their risks. Even so, there are some medications that are known to represent a hazard to human reproductive health and include, but are not limited to, routine use of non-steroidal anti-inflammatory medications, corticosteroids, and oral contraceptives. Even some dietary components have been linked with adverse effects on reproduction. For example, phytoestrogens, estrogenic chemicals present in plants such as soy proteins, have been linked to fertility problems in sheep and parrots, although there are no similar problems reported for the human population. In contrast, consumption of large amounts of vegetables and fruits containing b-carotene, a chemical present in carrots, sweet potatoes, squash, spinach, broccoli, mangos, and cantaloupe, has been linked with impaired fertility in a small group of women. Thus, some medications and even some natural constituents of our diet, not normally thought to be a source of potential problems, if present at high enough concentration or consumed consistently for protracted periods of time, can pose a risk to human reproductive function.

 

Cigarette smoking represents a significant and established risk to human fertility. Exposure to tobacco smoke includes both intentional (smoker) and unintentional (second hand smoke) exposures. Epidemiological studies have demonstrated that female smokers enter menopause approximately two years ahead of non-smokers. In men that smoke, there is a greater risk of sexual dysfunction and decreased semen quality. My laboratory has also shown that fertility rates in women who are exposed to second hand smoke are similar to those of women who smoke, and the fertility rates in both groups of women are about half as high as the pregnancy rates seen in non-smokers. Therefore, the conclusion is that exposure to tobacco smoke has a negative impact on human fertility, an effect that appears to extend to women with second hand smoke exposure as well. Tobacco smoke is composed of a vast number of chemicals and only a few have been studied for their effects on the reproductive system. Animal experiments have shown that some chemicals present in tobacco smoke, such as benzo[a]pyrene, nicotine, and cadmium, are toxic to the development of sperm, eggs, and embryos. Whereas dietary chemicals represent one end of the spectrum, and cigarette smoke constitutes the other end, the evidence for environmental contaminants places them somewhere in between these two groups in terms of their effect on fertility.

 

Numerous studies of semen quality have appeared in recent years, but there is no conclusive evidence that semen quality has changed over time. In Canada, we have shown that there are some regions where semen quality is lower than others, but no studies have been undertaken to explore potential causal relationships. Indeed, there is very little information to be found relating changes in semen quality with direct measurements of exposure to chemical contaminants, and thus it is not possible to draw any conclusions about the potential role of environmental contaminants in changes in human semen quality. Regardless, occupational exposure to pesticides has been linked with decreased semen quality, infertility, and spontaneous abortion. Conclusive results have been demonstrated for occupational exposure to some chemicals where the exposure is well defined. The pesticide Dibromochloropropane was convincingly linked to decreased semen quality and infertility in a population of workers exposed to this compound through manufacturing. In a Canadian study, exposure to a mixture of pesticides was associated with an increased risk of spontaneous abortion. However, other studies exploring the association between exposure to pesticides and reproductive function have failed to find a positive association. Results are highly conflicted, with some studies finding adverse effects whilst others find none. Reasons for failure to detect any relationship may be related to the small sample size of the studies, as well as the low frequency of the adverse outcomes being studied. Hence, the effect of pesticides on human reproduction remains controversial.

 

Chemical contaminants are widely distributed in our environment and are commonly measured in our food, air and water. While there is evidence of human exposure to some chemicals, this is not the case for most chemicals in use today. It is important to note that measurement of chemical contaminants in our environment cannot be taken as evidence of human exposure or presence of adverse health effects. Although present in the environment, some chemicals are measured in a small proportion of study subjects and the levels measured tend to be near the limit of instrument detection. Furthermore, many chemicals have inherently low biological activity whereas for others, exposure is thought to be below a threshold needed to induce an adverse health effect. Therefore, we need to be concerned about those chemical contaminants for which exposure is above the threshold needed to cause adverse effects. For the purposes of our discussion we will refer to chemical exposures that include solvents, polyhalogentated aromatic hydrocarbons, pesticides, metals, and plasticizers.

 

The literature is replete with animal studies that demonstrate that exposure to environmental contaminants from several different chemical classes is associated with adverse reproductive outcomes.

  

Of the vast array of environmental contaminants present in our environment, recent concern has focused on those chemicals that demonstrate hormone-like activity. Indeed, it is now well established that some environmental contaminants can mimic hormone effects through several different means that include: mimicking gonadal steroid hormone activity; increased metabolism of gonadal steroids (estrogen, progesterone and testosterone); inhibition of steroid hormone activity; increased production of these hormones; and direct toxicity to cells of the reproductive tract. Examples of chemicals belonging to this group of chemicals include Bisphenol A, phthalates, dioxins, polychlorinated biphenyls and many pesticides. While these compounds have been associated with adverse health effects in wildlife, fish, and experimental animals as noted above, there is much less certainty about their effects in the general human population. For example, while Bisphenol A, a chemical is widely used in the manufacture of plastic bottles, dental sealants, and the lining of tin cans, has received considerable media attention in recent months, there is a paucity of information concerning human exposure. Of greater concern is the conspicuous lack of data on any adverse health effects, despite reports of effects on reproduction in animals. Another point of concern is seeming impossibility of reproducing the results of some of the animal studies. On a reassuring note, other studies have shown that high concentrations of this chemical are needed to produce adverse effects. Chemical contaminants that are emerging as potential health concerns include stain-resistant compounds (perfluorochlorinated chemicals), flame retardants (polybrominated dipheyl ethers), and cosmetics (parabenes). However, the level of potential reproductive hazards and risks associated with exposure to these chemicals is unknown. Of potentially greater concern are several studies that have shown that prescription medications such as anti-inflammatory drugs and oral contraceptives are present in municipal waste-water treatment plant effluent. These data suggest that prescription medications may need to be added to the list of known environmental contaminants. Presence of these chemicals in environmental samples is troubling as they are profoundly more biologically active and potent than chemicals traditionally viewed as environmental contaminants.

 

Finally, in recent years, natural or complementary (alternative) medicines (black cohosh, Echinacea, evening primrose oil, and pregnancy tea, for example) have emerged as major commercial health products. However, their efficacy in many cases has not been proven nor has their safety been examined experimentally. While use of alternative medicines is generally thought to be safe and to pose no threat to human health, studies continue to appear in the scientific and medical literature that cause many scientists concern. The fact that a chemical occurs naturally in the environment cannot be taken as an endorsement of its safety. For example, lead, cadmium, arsenic, copper, cyanide, and aphlatoxin are all naturally occurring chemicals with well-documented health effects, including adverse effects on reproductive physiology. Therefore, even with naturally occurring substances and health products, caution must be exercised. Consulting a physician, pharmacist, registered dietician or toxicologists may be helpful before beginning to use these agents.

 

In order to understand the impact of chemical exposures on human health and fertility, exposures are placed according to whether they pose a hazard or a risk to fertility, relative to all other exposures people may encounter in the course of their daily activities. To address this problem, a 10-point scale is proposed to establish both hazard and risk scores for different contaminants that Canadians may encounter during a regular day. Specifically, it is proposed that no hazard would be scored as zero, whereas an established hazard to fertility would be assigned a value of 10. A similar approach could be taken when estimating risk to human reproductive health. It is possible that, under this system, a chemical could have a high hazard score and a low risk score, reflecting evidence from animal studies of effects on reproduction. However, the absence of evidence of human exposure, and a low potential for adverse effects in people because of differences in mechanism of action or physiology between experimental animals and humans means that the risk for humans is still considered low. Through this approach it is hoped that the reader will be provided with insight into the relative hazard and risk represented by exposure to environmental chemicals. It must be appreciated that scoring chemicals is a complex and difficult task that is accomplished using a weight-of-evidence approach, involving criteria such as consistency of the data, biological plausibility, experimental evidence for an adverse effect on fertility and evidence of exposure. These scores are determined by the most recent data, and they will change as new information becomes available.

 

In summary, despite the commonly held view of a trend towards increased numbers of infertile Canadian couples, recent evidence does not support this notion. Estimates show that environmental contaminants are recognized hazards to reproductive health. However, risk estimates are generally low owing to low potential for human exposure, lack of evidence of exposure, and absence of evidence for effects in humans. Continued investigation of the links between exposure to chemical contaminants, new chemicals and reproductive function will be required to characterize hazards and define health risks associated with these exposures.