| Androgen disrupting chemicals (ADCs), namely androgens and antiandrogens, are endocrine disrupting chemicals (EDCs) that mimic or antagonize the effect of physiological androgens, respectively. The objective of this dissertation was to link ADC-induced alterations revealed by different biomarkers to obtain a gene signature for the effects of a short-term exposure to ecologically relevant levels of three ADCs [11-ketotestosterone (11-KT), flutamide (FLU) and vinclozolin (VIN)], on a sensitive fish model. Early development stages of the Sacramento perch, a native California fish, were characterized from fertilization and organogenesis until the onset of exogenous feeding to evaluate its potential as a model for androgen disruption screening and testing. There were no sexually dimorphic characteristics on the early life stages of the Sacramento perch. Hence, Qurt strain medaka was considered more amenable for further studies. One-week-old medaka larvae were exposed to 11-KT and FLU to evaluate effects on survival, growth and tissue structure through gross morphology and histopathological biomarkers. There was no significant acute mortality, except for males treated with FLU (96h-LC50 = 1.92 mg/l). Gender-specific effects in growth were identified after 11-KT and FLU treatments. Histopathological alterations including thyroid follicular hyperplasia, germ cell necrosis, ovarian atresia, and testis-ova were observed in medaka at 90-d post-exposure. The lowest observed effective concentration (LOEC) for testis-ova induction in Qurt medaka males was 0.320 mg/l. Biologically effective concentrations (BECs) for 11--KT (100 mug/l), FLU (1000 mug/l), and VIN (100 mug/l) were first determined in range-finding studies. The identified BECs were used as exposure concentrations for characterizing the microarray-based response to each ADC. A custom medaka oligonucleotide microarray, coupled with robust statistical techniques, was used to identify a diagnostic set of genes that generate a distinctive pattern for androgenic and anti-androgenic substances. An initial screening using VIN as a test compound revealed that it followed an antiandrogenic pattern of gene expression. In addition, there was differential expression of 14 out of 50 gene transcripts with putative roles in sex determination, sex differentiation and growth in medaka and other vertebrates. |
