Environmental contaminants and mammalian reproductive health Event

Declining fertility in humans and animals has been attributed to exposure to anthropogenic environmental chemicals which are ubiquitous in the environment. In the human, increasing incidences of testicular cancer, cryptorchidism, hypospadias and declining sperm counts, collectively referred to as testicular dysgenesis syndrome (TDS), have been recorded in recent decades. The rationale behind the linkage of these problems lies in the fact that they occur, together, in specific geographical areas. Evidence is also beginning to emerge that female reproductive health may also be affected with studies claiming a link between exposure to environmental chemicals and breast cancer, precocious puberty, PCOS, infertility and endometriosis. Many of the chemicals interfere with the endocrine system and are referred to as endocrine disrupting chemicals (EDCs). However a wide range of other biological and physiological systems appear to be perturbed, many of which are crucial for reproductive development. Indeed, the periods of fetal and post-natal development are particularly sensitive to exposure. Studying the effects of these contaminants in the human requires the use of suitable animal models. We have used two sheep models where pregnant ewes are exposed to environmental concentrations of chemicals. In the first model, pregnant ewes are exposed to a “cocktail” of chemicals contained within sewage sludge pellets spread on pasture as a fertiliser. This is therefore representative of “real life” exposure. In the second model, pregnant ewes were exposed to selected chemicals known to accumulate in ovine fetuses from the first model. In both paradigms, we have shown marked effects on the developing fetal hypothalamic pituitary gonadal axis and in relation to the sewage sludge model, a subset of ram offspring have shown altered testicular morphology and behavioural changes. Although the sheep is an excellent experimental model, the dog is a sentinel for human exposure to contaminants since it occupies the same environment. A decline in semen quality from stud dogs used for a breeding program at the Guide Dogs for the Blind Association (UK) parallels that reported in the human and is also thought to be environmental rather than genetic. In support of this we have detected chemicals with known endocrine disrupting activity in food and in testes obtained from routine castrations. Our data support the hypothesis that environmental concentrations of EDCs perturb mammalian reproductive health and fertility and that the combined use of experimental and sentinel animal models is essential in determining the reproductive consequences of endocrine disruption.