Reproduction in Domestic Animals

Reprod Dom Anim 43 (Suppl. 2), 15–22 (2008); doi: 10.1111/j.1439-0531.2008.01138.xISSN 0936-6768Endocrine Disruptors and Other Food-contaminating Environmental Pollutants asRisk Factors in Animal ReproductionSM RhindMacaulay Institute, Aberdeen, UKContentsPollutants of many chemical classes, derived primarily fromanthropogenic activities, are ubiquitous in the environment,persistent, biologically available and can exert adverse effectson the reproductive and other, indirectly related, physiologicalsystems. Food is generally considered to be the major route ofanimal exposure in vertebrate species but the relative contributionsof other routes of exposure such as through lungs, gillsor skin are not well studied and may be of importance forcertain animal groups, depending on their immediate environment.Animals are particularly sensitive to exposure duringdevelopmental stages but the pattern of exposure to chemicalsis likely to be different to that of adults. Quantification of therisk posed by the ingestion of pollutants in food is complexand depends on many factors including species, diet composition,duration of exposure to the food, efficiency of pollutantabsorption, subsequent metabolism, sensitivity of targetorgans and stage of development. While the effects of highdoses of single chemicals are proven, dietary exposure topollutants generally involves prolonged, low-level exposure toa large number of compounds, each of which has differentchemical characteristics, exerts different biological effects andis present at varying concentrations. Thus, while exposure topollutants through feed is undoubtedly a significant risk factorfor many species and may be the most important one for manyterrestrial vertebrates, other routes of exposure may be moreimportant in other groups.IntroductionExposure to pollutants, and in particular to endocrinedisrupting compounds (EDCs) and potentially toxicmetals (PTMs) can induce adverse physiological changesin animals of every group so far studied, from bacteria(Fox 2004) to humans (Toppari et al. 1996) and animalsof many phyla in between (Institute for Environmentand Health 1999). Many of the effects pertain to thereproductive system (Toppari et al. 1996; Paul et al.2005; Uzumcu and Zachow 2007, Fowler et al. 2008) butother physiological systems can be perturbed by exposure.These include the thyroid gland (Hansen 1998),neuroendocrine system (Lein et al. 2007) and thereforebehaviour (Erhard and Rhind 2004), the immune system(Vine et al. 2000; Daniel et al. 2001) and systems thatcontrol adipogenesis and nutrient partitioning (Newboldet al. 2007); disruption of these physiologicalsystems may also impinge on reproductive fitness.Evidence of relationships between exposure to pollutantsand reproductive effects is derived from observationalstudies of wildlife exposed, unintentionally, topollutants (Smith 1981; Guillette et al. 1994; Institutefor Environment and Health 1999) and from empiricalstudies of laboratory and domestic animals or cellcultures (Gray et al. 2000; Meerts et al. 2001; Evanset al. 2004). The reproductive systems of animals ofmany phyla have been found to be perturbed throughmany mechnisms (Table 1). The first type of studyserved to demonstrate associations between EDC exposureand adverse effects on reproductive function whilethe latter has begun to elucidate mechanisms of action.However, even if they have involved administration ofchemicals in feed, some controlled studies are poorrepresentations of normal real-world exposure throughfood, being based on single chemicals, often at very highconcentrations, and administered for short periods.The aim of this paper is to review what is known ofthe risks of exposure to pollutants through the diet andto identify some principles that pertain to their effects onreproductive function in general, irrespective of speciesand habitat.What Classes of Chemical are Involved andHow Do They Operate?The acute toxicity of high levels of PTMs has probablybeen recognized since metals were first smelted. However,recent reports indicate that they may also exertmore subtle effects and that very low, environmentallyrelevant, concentrations of cadmium, copper, cobalt,nickel, lead, tin and mercury can each activate theoestrogen receptor a (Martin et al. 2003; Henson andChedrese 2004) while methyl mercury can disrupt nonsteroidalreceptors (Klaper et al. 2006) and copper cancompromise olfactory or other senses in fish (Sandahlet al. 2007). Thus, each has the potential to disruptreproductive function.Organic EDCs, unlike PTMs which can also actthrough endocrine disruption, are primarily anthropogenicin nature and have been produced in largeamounts only for approximately 60 years, only. Classesand sources of EDCs have been described previously(Rhind 2005). They seldom induce an acute toxic effectbut can affect reproductive function at concentrationsmany orders of magnitude below the toxic dose. Theseeffects are expressed through many mechanisms includingbinding to the androgen receptor (DDT metabolites;Kelce et al. 1998), oestrogen receptor [alkyl phenols andpolychlorinated biphenyls (PCBs); Dodge 1998] and arylhydrocarbon receptor [polycyclic aromatic hydrocarbons(PAHs); Haque et al. 2005]. In addition, PCBs canact directly on cellular systems via non-receptor-mediatedsystems (Li and Hansen 1996). It is noteworthy thatthe DNA of the oestrogen receptor appears to be highlyconserved over a very wide range of phyla and species,suggesting that it is evolutionarily ancient (ThorntonÓ 2008 Macaulay Land Use Research Institute