Effects of in-utero exposure to environmental chemicals via maternal pasture ingestion on fetal development. (360G-Wellcome-080388_Z_06_Z)

Current understanding of possible detrimental effects of exposure to environmental chemicals (ECs) on fetal reproductive development relies on toxicological studies of short-lived rodents exposed to high doses of single/small numbers of compounds. We will employ a long-lived species, the sheep, to investigate effects on fetal development of a real-life , chronic, low-level exposure of ewes to a relevant cocktail of ECs, including endocrine disrupting compounds (EDCs and heavy metals. Ewes will be maintained on pastures fertilised with either inorganic fertiliser (Control) or sewage sludge (EC cocktail). Maternal and fetal EC levels will be measured and related to endocrine systems and hypothalamo-pituitary and gonadal development and function at 55 & 110 days of gestation, and in adult offspring. Specific effects of fetal exposure via continuing maternal intake of ECs will be distinguished from those solely due to mobilisation of maternal EC loads. This will be done by switching Contr ol ewes to sewage sludge-fertilised pastures, and vice versa, immediately prior to mating, with slaughter at 110 days of gestation and measurements as above. Our key goals are to determine the extent to which EC exposure (1) disrupts fetal development, (2) compromises adult reproductive function and (3) relies on mobilization of maternal EC loads.