Acute developmental exposure to 4-hydroxyandrostenedione has a long-term effect on visually-guided behaviors

Neurotoxicol Teratol. 2017 Nov:64:45-49. doi: 10.1016/j.ntt.2017.10.003. Epub 2017 Oct 12.

Abstract

Estrogenic and anti-estrogenic endocrine disrupting compounds (EDCs) are recognized as critical modulators of neural development, including sensory system development. Using the zebrafish model, we tested the effect of transient developmental exposure to a known anti-estrogenic EDC on adult visually-guided behavior. In particular, we exposed zebrafish aged 24-hour post-fertilization (hpf), 72 hpf, or 7-days post-fertilization (dpf) to the aromatase inhibitor 4-hydroxyandrostenedione (4-OH-A) for 24h. After this time, the fish were removed from treatment, placed into control conditions, and reared until adulthood (3-4months) when visually-guided optomotor responses (OMR) were assessed. Our results show significant decreases in positive OMR in adults exposed to 4-OH-A at 72 hpf and 7 dpf. These deficits were not accompanied by changes in overall swimming behaviors and startle responses, suggesting 4-OH-A specifically effected the visual system. Overall, this study identified long-term, quantifiable effects in visually-guided adult behaviors resulting from transient developmental exposure to the anti-estrogenic EDC, 4-OH-A. Further, these effects were noted when 4-OH-A exposure occurred after hatching, suggesting estrogen signaling is important for visual system maturation.

Keywords: 4-OH-A; EDCs; Endocrine disruptors; OMR; Optomotor response; Zebrafish.

MeSH terms

  • Androstenedione / administration & dosage
  • Androstenedione / analogs & derivatives*
  • Animals
  • Aromatase Inhibitors / administration & dosage*
  • Behavior, Animal / drug effects
  • Embryo, Nonmammalian / drug effects
  • Embryonic Development / drug effects*
  • Endocrine Disruptors / administration & dosage*
  • Photic Stimulation
  • Psychomotor Performance / drug effects*
  • Vision, Ocular / drug effects*
  • Visual Perception / drug effects
  • Zebrafish

Substances

  • Aromatase Inhibitors
  • Endocrine Disruptors
  • Androstenedione
  • formestane