The significance of antiandrogens in disrupting sexual function in wild fish in UK rivers.

Up to half of the water flowing in some UK rivers originates from the effluent of wastewater treatment works (WwTW) and this can affect the native wildlife. Several years ago we found that the reproduction in fish living in many UK rivers had been damaged by exposure to chemicals contained in the WwTW effluents that disrupt the body's sex hormone systems. The chemicals identified were oestrogens (female sex hormone) and included natural oestrogen hormones, pharmaceutical oestrogens taken by women as part of the contraceptive pill, and some industrial chemicals that mimic oestrogens because they are similar in structure. Feminised fish in the wild is of concern because we have shown that they have a reduced capacity to breed and this may lead to adverse effects for the population. Disorders in male human reproductive health occur that are very similar in nature to effects seen in wild fish and some of these effects have been associated with exposure to EDCs. Studies in the laboratory with fish have shown that it is possible to induce some of the feminised responses occurring in wild populations with the environmental oestrogens identified. Recently however, we have found that effluents throughout the UK contain anti-androgenic activity in addition to oestrogenic activity / anti-androgenic activity would suppress the normal male sex hormone system (androgens) and thus also feminise males. For some effluents the potency of the anti-androgenic activity was very high and there is an urgency to identify the chemicals of concern, not least because they may have adverse effects for humans too. In this proposal we intend to first identify the chemical structures responsible for the anti-androgenic contamination of UK WwTW effluents. This will be done by fractionating the test effluents and screening the fractions with a cell based assay that can detect anti-androgen activity. The chemicals with anti-androgen activity are ultimately identified using high resolution analytical chemistry techniques. This approach will also be undertaken using bile (a fluid found in a small sac as part of the liver) from fish exposed to WwTW effluent to find out which of the anti-androgens found in the effluents enter the fish and build up in their bodies. Many chemicals taken into the body undergo change (metabolism) and our team (EMH) has considerable expertise in recognising chemical structures derived from other chemicals taken in from the environment. We will then test how potent the anti-androgens identified are in fish by first measuring their ability to inhibit production of an androgen (male sex hormone) dependent protein called spiggin in the stickleback. In the final part of this work we will take the most potent anti-androgen found and expose roach (a fish in which disruption of sex in wild populations in UK rivers is well documented) from embryos and up to 1 year in age and measure a range of endpoints to assess how the chemical effects the development of sex (whether it becomes a male or female fish) and effects on the machinery required to produce eggs (females) and sperm (in males). This work will provide a more informed knowledge of the health impacts of EDCs for the better protection of our aquatic resources and biodiversity. Identification of anti-androgenic compounds in wastewaters, will also likely allow their sources to be identified and facilitate an assessment of exposure and risk to human health. The work will contribute to environmental impact assessments and have importance in the regulation of discharges and thus is of very wide interest to the government regulatory bodies, environment protection groups, industry and the wider public.