Gene signatures for endocrine disruptors
Chemicals that are classed as endocrine disruptors can cause deleterious effects on health as a whole by changes in endocrine or hormonal function. If the reproductive system is affected, this is not only significant for the individual but for its progeny as results of possible gene deregulation may be passed onto future generations. The nature of endocrine disruptors and their use in industry is very varied. Five endocrine disruptors (EDs) including the insecticide lindane and an oestrogen mycotoxin were tested. The chemicals were administered to mice in their drinking water at three different concentrations. To assess the effects of the EDs at various stages of development, the dosages were given to the mothers before mating, during pregnancy and maintained for four weeks after the birth. To analyse the extent of endocrine disruption, the resulting transcriptomes were analysed. This gives a pattern of data based on how gene expression may have been changed by the chemical. Comparative analysis of all the data yielded gene expression signatures. It was found that most of the EDs under study gave a distinctive array indicating a specific pattern of gene deregulation. In particular, oestradiol (the female hormone), monoester of ethyl hexyl phthalate (a plasticiser) and zearalenone (the oestrogenic mycotoxin) showed defined arrays. To utilise these results on a commercial scale, and to facilitate the analysis of the effects of EDs in general, microarrays can be constructed using data of this nature. After validation of results obtained from microarray analysis, a selection of specific genes can be processed to create a specific GENDISRUPT microarray. This could be patented and used in the assessment of chemicals suspected of endocrine disruption in animal models.
