Transcriptional responses in male Japanese medaka exposed to antiandrogens and antiandrogen/androgen mixtures

• DOI: 10.1002/tox.22163
• Publication Date: 2015-06-22T11:44:52Z
• Authors: Liwei Sun; Tao Peng; Fang Liu; Lin Ren; Zuhua Peng; Guorong Ji; Yinfang Zhou; Zhengwei Fu
• Keywords: Male; Transcription, Genetic; Oryzias; Androgen Antagonists; Endocrine Disruptors; 01 natural sciences; Androgens; Animals; 14. Life underwater; Gonads; Water Pollutants, Chemical; 0105 earth and related environmental sciences

ABSTRACTThe occurrence of androgenic endocrine disrupting chemicals (EDCs) in water is thought to be linked to deviation from normal male developmental and reproductive functions in exposed aquatic organisms. Because aquatic environments represent a chemically complex medium, the combined effects of androgenic EDCs require urgent attention. In the present study, the effects of two model androgen receptor (AR) antagonists, flutamide (FLU), and vinclozolin (VIN), were first determined individually in male Japanese medaka using the transcriptional response for genes associated with the hypothalamic‐pituitary‐gonadal axis. The fish were further exposed to binary mixtures of VIN and 17β‐trenbolone (TRE, AR agonist) to confirm the theoretical opposing effects of the AR antagonist and agonist. The results showed that exposure to FLU or VIN alone induced very similar transcriptional responses, demonstrating that gene transcription analysis could be successfully employed in identifying the action of single chemicals. For example, both exposures increased the transcription of cyp17b but decreased that of cyp19b in the gonad, demonstrating the compensatory response for AR blockage. However, in the case of exposure to mixtures, although the joint antagonistic action of TRE and VIN affected the most genes, the transcription profiles after exposure to mixtures were not consistent with expectations based on the results for individual chemicals, such as hepatic vtg, and star or cyp19a in gonads. Therefore, the limitation of gene transcription analyses in exposures to mixtures, as well as the potential for the extrapolation of single chemicals, should be considered in future studies. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1591–1599, 2016.