Authors
Richard M. Sharpe

Title
Environment, lifestyle and male infertility

Journal
Bailliere's Clinical Endocrinology and Metabolism 14(3) 2000

Summary
The objective of this paper is to review some of the environmental and lifestyle factors affecting sperm count and fertility. The extreme variation in sperm count and ejaculate between individuals in the general population has posed a constraint in studying the relationship between a particular environmental factor, lifestyle or occupation and a reduced sperm count and/or fertility in the human male. Due to this variation, a large number of subjects would need to be studied, thus increasing costs and ruling out many studies.

The enormous variation in sperm count among men is related to the number of Sertoli cells in the testes. These unique cells control the development of germ cells into spermatozoa. Each Sertoli cell supports a fixed number of germ cells by providing an environment within the seminiferous tubules in which germ cells develop and by providing a physical and nutritional support for these cells. A simple linear relationship between Sertoli cell number and daily sperm production has been established. However, Sertoli cell number varied more than 50-fold among the men. The factors involved in Sertoli cell number variation remains unknown; however, the neonatal (0-9 months) and the peri-pubertal periods are the most crucial times for Sertoli development. In this regard, early life events are potentially important in determining male reproductive development and function. In addition, genetic differences among men may also play a role, as evidenced in studies of infertility and low sperm count in brothers.

The organization of the stages of spermatogenesis in human males is different from that of species with highly efficient spermatogenesis. The poor efficiency ('efficiency' referring to the number of germ cells that each Sertoli cell supports) of spermatogenesis in the human male may make him more susceptible than other species to the adverse effects of environmental factors. Under normal conditions, human males also produce a high proportion (>50%) of morphologically abnormal sperm incapable of fertilizing. Primates (i.e. chimpanzees) that have an organization of spermatogenesis similar to that of the human also have a reduced efficiency of spermatogenesis. Since it is not just man who exhibits this phenomenon, it can be said that lifestyle and environmental factors do not affect spermatogenesis efficiency.

A study conducted in Denmark compared the sperm count in two groups of nearly 200 young men, one group from a rural and one from an urban population. A higher median sperm count (24%) was found in men from the rural group than in those from the urban group. In addition, blood levels of follicle-stimulating hormone (FSH) and inhibin B (a hormone influenced by alterations in Sertoli cell number) were also significantly different in the two groups (the inhibin B level bein higher and the FSH level lower in the group with the highest sperm count). Thus, a well-designed study involving a large number of men and measuring a combination of blood hormone and sperm count may be a more accurate approach to establish the relationship between occupation/environment and human testis function.

A significant relationship between scrotal temperature and sperm count has been established in recent years. The sedentary lifestyle of men of all ages may impair the ability of the scrotum to thermoregulate. Men with more sedentary lifestyles or occupations have higher average scrotal temperature. In turn, an elevation of scrotal temperature to normal core body temperature results in a failure of spermatogenesis. This effect is probably at its worst in paraplegic men. A study of normal young men showed that an elevation of scrotal temperature by as little as 0.7C for 75% of the working day was sufficient to significantly impair semen quality. A rise in scrotal temperature may increase the number of abnormal sperm, decrease sperm motility and/or decrease the number of sperm in the ejaculate. These effects may lead to impaired fertility and can affect implantation and early embryo development as the miscarriage rate is significantly elevated in female animals after mating with an "affected" male.

Events occurring during fetal and neonatal development of the testis are believed to be critical in determining reproductive abnormalities, including low sperm count and infertility. For example, testicular germ cell cancer (approximately 90% of cases occurring in the age range of 15-45 years) originates from abnormal gonocytes in the testis that developed in fetal life and activated to grow into a tumour post-pubertally. In addition, developmental disorders of the reproductive system, such as cryptorchidism and hypospadias, and factors such as low birth weight, are important risk factors of testicular cancer. In this context, testicular cancer is associated with reduced semen quality and reduced fertility, both of which are evident long before tumour development. The neonatal rather than fetal life may be more important as the period of most rapid Sertoli cell proliferation in the first 6-9 months postnatally. Since the number of Sertoli cells is so critical in determining sperm production, it is possible that events in the first year of life will likely influence sperm production in adulthood by affecting Sertoli cell proliferation.

The incidence of testicular cancer has increased significantly throughout much of the world over the past 50-100 years century. This clearly suggests that lifestyle and/or environmental factors are having a profound negative effect on early male reproductive development. For example, a high level of a range of pesticides is detectable in human adipose tissue. Lipid-soluble pesticides accumulating in fat raises concerns regarding the transmission of such compounds from the mother to the breast-feeding infant. Indeed, the first-born infants of older mothers would be those most highly exposed in this way. However, it is unknown whether this is a contributing factor towards human reproductive development or function.

Given the central role that hormones play in guiding the development of the reproductive system, it is not surprising that a major focus of endocrine disruption research has been on reproductive health. Over the last decade, a large number of hormonally active compounds have been discovered. Not only are more compounds involved, but more hormone systems are now known to be vulnerable and new mechanisms of interaction between compounds and receptor systems have been explored to understand the way(s) by which a compound exerts its effects. Until recently, research has been focused on the oestrogenic activity of various chemicals in plastics (i.e. phthalates), pesticides (i.e. DDT), products of combustion (dioxins), polychlorinated biphenyls (PCBs) and many more. Most of these compounds appear to be very weak oestrogens that it is unlikely that they pose a significant risk to sperm count or fertility.

The nematocide dibromochloropropane (DBCP) is the only pesticide that has been unequivocally shown to lead to a major decrease in sperm count and infertility after human exposure. While this compound is still being used in some developing countries it is important to note that its effects on semen quality are not believed to be through an endocrine mechanism but rather involves direct toxicity to the spermatogonia. Animal studies have resulted in conflicting conclusions regarding the relationship between endocrine disruptors and the incidence of testicular cancer and decreased sperm production. However, it has recently been determined that several phthalates are potent anti-androgens and thus of concern considering the key role of androgens in male reproductive development. A recent study has reported that PCBs, at a very low concentration, can prolong the bio-activity of endogenously produced estrogens by inhibiting oestrogen sulphotransferase, a key enzyme that inactivates oestrogens in the body. Since the human male fetus develops in an environment consisting of oestrogens, any changes in the production, action or metabolism of endogenous hormones as a result of exogenous chemical exposure could potentially alter endogenous oestrogen exposure by the fetus.