Endocrine disrupting chemical impacts on eukaryotes

Endocrine Disrupting Chemicals (EDCs) are exogenous substances or mixtures that might lead to endocrine disruption in humans and wildlife. Bispheriol (BPA) was chosen as a model EDC and assessed for its toxic impacts on two eukaryotic test systems: (1) A fungal test system - white-rot basidiomycete, Trametes versicolor T. versicolor was tolerant of high concentrations of BPA (up to 300 ppm). The ligninolytic enzymes produced by the fungi were stimulated by 300 ppm of BPA. Of the three ligninolytic enzyme encoding genes examined, lignin peroxidase showed the greatest increase in expression in the presence ofBPA. (2) A mammalian test system - mouse Leydig tumor cell lines (mLTC-l) Time- and dose-responses of the cells stimulated with gonadotrophin to BPA demonstrated the clearest response in the expression of the steroidogenic genes without a marked effect on cell viability. The studies on the response of global gene expression to BPA by microarray analysis of mLTC-l cells showed 24 genes were differentially expressed in the presence of BPA (8 were increased and 16 were decreased). Several of these genes were related to steroid/cholesterol metabolism, transport and cell cycle regulation. In addition a study of male reproductive impairment was carried out to understand the reproductive toxicity of EDCs and likely effects on male infertility - one of the serious effects caused by EDCs. Human testicular tissues from fertile and infertile patients were examined by a microarray and 2642 genes were differentially expressed between the testes of fertile and infertile patients (955 genes were increased and 1687 genes were decreased in infertile patients). These genes are related to steroidogenesis, Leydig cell function, spermatid metamorphosis, cell cycle, and ribosome function. The array data exhibited phenotype-specific gene expression patterns. The most significant gene expression differences between fertile and infertile. patients were observed in spermatocyte- and spermatid- stages. Though further analysis is required, it is thought that BPA has weak modulatory impacts on eukaryotic test systems used in this study, however, its reproductive toxicity may not be negligible.EThOS - Electronic Theses Online ServiceGBUnited Kingdo