Rapid fluorescent detection of (anti)androgens with spiggin-gfp medaka

Environ Sci Technol. 2014 Sep 16;48(18):10919-28. doi: 10.1021/es5030977. Epub 2014 Aug 29.

Abstract

Widespread environmental antiandrogen contamination has been associated with negative impacts on biodiversity and human health. In particular, many pesticides are antiandrogenic, creating a need for robust and sensitive environmental monitoring. Our aim was to develop a sensitive and specific transgenic medaka (Oryzias latipes) model bearing an androgen responsive fluorescent reporter construct for whole organism-based environmental screening of pro- and antiandrogens. We analyzed the 5' regions of the androgen responsive three-spined stickleback (Gasterosteus aculeatus) spiggin genes in silico, revealing conserved blocks of sequence harboring androgen response elements. Identified putative promoters were cloned upstream of GFP. Germinal transgenesis with spg1-gfp led to stable medaka lines. GFP induction was exclusive to the kidney, the site of spiggin protein production in sticklebacks. Significant GFP expression was induced by three or four-day androgen treatment of newly hatched fry, but not by estrogens, mineralocorticoids, glucocorticoids or progestogens. The model responded dose-dependently to androgens, with highest sensitivity to 17MT (1.5 μg/L). In addition to flutamide, the biocides fenitrothion, vinclozolin and linuron significantly inhibited 17MT-induced GFP induction, validating the model for detection of antiandrogens. The spg1-gfp medaka model provides a sensitive, specific, and physiologically pertinent biosensor system for analyzing environmental androgen activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / metabolism*
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Cloning, Molecular
  • Fish Proteins / metabolism*
  • Fluorescence
  • Green Fluorescent Proteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Oryzias / genetics
  • Oryzias / metabolism*
  • Promoter Regions, Genetic / genetics
  • Receptors, Androgen / metabolism
  • Smegmamorpha

Substances

  • Androgen Antagonists
  • Fish Proteins
  • Receptors, Androgen
  • spiggin
  • Green Fluorescent Proteins