There is a large body of evidence that when a developing foetus is exposed to environmental chemicals (ECs), its future reproductive potential may well be reduced. These ECs include endocrine disrupting compounds (EDCs), and their adverse effects are seen in wildlife, domestic species and humans. Currently scientists and medical doctors think that such exposure to ECs is part of the mechanism increasing the rates of reproductive defects and infertility in males and females. Just one example is the 2% annual increase in EU breast cancer rates. Studies on a wide range of ECs, including the plasticisers, phthalates, and many other chemicals (e.g. PCBs, BPA and dioxins), show that the female reproductive tract is sensitive to damaging effects of chemicals. In the past, many studies have focused on single or small numbers of ECs, on short-lived rodent species, and have used high doses of the chemicals. These patterns of exposure to chemicals is completely different from how humans are exposed to ECs. We will use two different animal models in REEF. The sheep, exposed to sewage sludge treated pastures, provides a model of real-life exposure to a broad range of ECs at low/environmental concentrations. Sheep are long-lived and have many reproductive similarities with humans. The mouse will be used to study the mechanisms by which ECs interfere with reproduction. We will use both models to study whether the effects of chemicals on a developing foetus are passed on to her offspring in turn. We already know that di-2-ethylhexylphthalate and two PCBs accumulate in the sheep foetus following exposure of their mothers. We will therefore investigate effects of combinations of these chemicals on both the foetal sheep and mouse ovaries. EC-sensitive genes and proteins identified in our animal studies will act like signposts for studies of normal second trimester human foetal ovaries, in order to better understand the risks of ECs on human female reproductive development in the womb.