Abstract

Estrogen-specific endocrine disrupting compounds (EDCs) are potent modulators of neural and visual development and common environmental contaminants. Using zebrafish, we examined the long-term impact of abnormal estrogenic signaling by testing the effects of acute, early exposure to bisphenol-A (BPA), a weak estrogen agonist, on later visually guided behaviors. Zebrafish aged 24 h postfertilization (hpf), 72 hpf, and 7 days postfertilization (dpf) were exposed to 0.001 μM or 0.1 μM BPA for 24 h, and then allowed to recover for 1 or 2 weeks. Morphology and optomotor responses (OMRs) were assessed after 1 and 2 weeks of recovery for 24 hpf and 72 hpf exposure groups; 7 dpf exposure groups were additionally assessed immediately after exposure. Increased notochord length was seen in 0.001 μM exposed larvae and decreased in 0.1 μM exposed larvae across all age groups. Positive OMR was significantly increased at 1 and 2 weeks post-exposure in larvae exposed to 0.1 μM BPA when they were 72 hpf or 7 dpf, while positive OMR was increased after 2 weeks of recovery in larvae exposed to 0.001 μM BPA at 72 hpf. A time-delayed increase in eye diameter occurred in both BPA treatment groups at 72 hpf exposure; while a transient increase occurred in 7 dpf larvae exposed to 0.1 μM BPA. Overall, short-term developmental exposure to environmentally relevant BPA levels caused concentration- and age-dependent effects on zebrafish visual anatomy and function.

Highlights

  • Endocrine disrupting compounds (ECDs) are exogenous chemicals of natural and synthetic origin that affect hormonal function, synthesis, and/or downstream signaling pathways [1,2]

  • While endocrine disrupting compounds (EDCs) are most noted for their influence on reproductive physiology, especially on estrogens and estrogenic pathways, developmentally irregular estrogen synthesis is associated with thinning [10] and apoptosis in retina [11], corneal thinning [12], and abnormal and delayed eye growth [13]

  • Age-related estrogen level changes in humans are associated with neurodegenerative retinal diseases [14] and estrogen modulation as a clinical treatment for breast cancer has been linked to retinal hemorrhaging [15], macular edema [16], and color perception changes [15], underscoring the role of estrogen-specific EDCs in more than reproductive development

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Summary

Introduction

Endocrine disrupting compounds (ECDs) are exogenous chemicals of natural and synthetic origin that affect hormonal function, synthesis, and/or downstream signaling pathways [1,2]. While EDCs are most noted for their influence on reproductive physiology, especially on estrogens and estrogenic pathways, developmentally irregular estrogen synthesis is associated with thinning [10] and apoptosis in retina [11], corneal thinning [12], and abnormal and delayed eye growth [13]. Age-related estrogen level changes in humans are associated with neurodegenerative retinal diseases [14] and estrogen modulation as a clinical treatment for breast cancer has been linked to retinal hemorrhaging [15], macular edema [16], and color perception changes [15], underscoring the role of estrogen-specific EDCs in more than reproductive development. Despite the viable connection between estrogen and vision, we still know very little about the long-term impact of altered estrogenic signaling on visual sensation, perception, and system development

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