Could hormone residues be involved?

In this issue, Swan et al. report finding a relationship between the amount of beef consumed by women during pregnancy and subsequent sperm concentration in their sons in adulthood. There is extensive evidence that maternal nutrition and maternal consumption of specific nutrients, drugs and chemicals present in food during pregnancy and lactation can have consequences for subsequent pathophysiology of offspring. This has been demonstrated experimentally in animals, and the developmental origins of human health and disease (DoHAD) hypothesis also has considerable support from the epidemiological literature (Fowden et al., 2006; Gluckman et al., 2007). Only recently have researchers interested in fetal nutrition and metabolic diseases become aware of findings relating developmental exposure to the class of environmental chemicals known as endocrine disruptors to metabolic and reproductive disorders in males. Specifically, Skakkebaek et al. (2001) have identified that a cluster of reproductive abnormalities in males (sperm quality and testicular cancer) is associated with conditions identifiable at or shortly after birth (cryptorchidism, hypospadias), which they have named the ‘testicular dysgenesis syndrome (TDS)’. This cluster of abnormalities of male reproductive development is proposed to be due, at least in part, to fetal/neonatal exposure to environmental estrogens (EE) [one example of such an EE is bisphenol A, the chemical used to make polycarbonate plastic and the resin lining of metal cans (vom Saal and Hughes, 2005)] and chemicals with antiandrogenic activity [one example would be phthalates used in PVC plastic and many other products (Swan et al., 2005)]. Skakkebaek’s hypothesis is thus that developmental disorders identifiable at birth are predictive of subsequent male reproductive system pathologies, such as reduced fertility due to low sperm count as well as testicular cancer. Although there are a number of potential factors that could account for the association reported in the current study by Swan et al., these authors suggest based on the Skakkebaek TDS hypothesis that the association between the number of beef meals eaten per week during pregnancy and sperm concentration in male offspring might be due to exposure to hormonal residues in beef. This hypothesis is plausible because during the years this cohort of fertile men were in utero (median year of birth was 1970), beef cattle in North America (where the majority of study participants were born) were routinely treated with the growth-promoting anabolic steroids. For example, the drug diethylstilbestrol (DES) was widely administered to beef cattle in the USA between 1954 and 1979 (Raun and Preston, 2002). Although the use of hormones to promote an increase in lean muscle mass in beef cattle has not been legal in Europe since 1989, and while DES was banned in 1979, administration of combinations of other hormonally active drugs to beef cattle has continued to be a common practice in the USA and Canada. The International Joint Food and Agricultural Organization’s World Health Organization Expert Committee on Food Additives (JECFA) published acceptable (tolerable) daily intake ADIs (TDIs) for all hormones in current use as growth promoters in beef cattle, although the assumptions used by JECFA to determine ‘safe’ daily human exposure levels in their 1988 report have been challenged (Andersson and Skakkebaek, 1999). There has been a trade dispute over the safety of hormone residues in beef going on for many years, with the European Union opposing importing hormonetreated beef from the USA and Canada. The position of the USA and Canada is that hormone residues in beef pose no threat to human health; this position is based primarily on research concerning the mutagenic activity of estradiol. Over the past decade, there has been a shift in the focus of research in endocrinology, cancer and developmental biology based on findings that hormones, hormonally active drugs and *In autumn 2006, the author served on the science advisory committee of the European Union regarding low-dose effects of xenobiotic estrogenic chemicals in food.

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