Fig. 11: Summary of BPA effects observed in adult retinas.

Schematic diagrams show the effects of low BPA (left) and high BPA (right) on estrogen signaling pathways when exposure occurred at 72 hpf (A) and 7 dpf (B). A Exposure to low (0.001 µM) BPA at 72 hpf activated both genomic and non-genomic estrogen signaling. Low BPA binding to intracellular ER increased cyp19a1b expression. In contrast, low BPA binding to ERβ was antagonistic, decreasing ERβ protein levels. Low BPA binding to GPER (dark blue) reduced p-ERK levels (−); while low BPA binding to membrane bound ER increased p-JNK levels (+). Functionally, low BPA exposure was associated with increased ERG responses, changes in GAD and TH protein levels, and reduced OMRs. High BPA (0.1 µM) exposure at 72 hpf (right) in contrast, lead to reduced p-ERK levels only, suggesting a specific effect on non-genomic pathways. This result was associated with increased GAD and TH levels in retinal homogenates, increased photoreceptor, but decreased ON-bipolar cell responses. B Exposure to low (0.001 µM) BPA at 7 dpf activated both genomic and non-genomic estrogen signaling. Low BPA binding to intracellular ER increased ERβ protein levels. Low BPA binding to GPER (dark blue), in contrast, reduced p-ERK (−) and p-AKT (−) levels. High BPA exposure at 7 dpf (right) activated non-genomic pathways only, increasing p-JNK (+) and p-AKT (+) levels. Functionally high BPA exposure at 7 dpf caused physiological changes in adult zebrafish retinas by increasing ON-bipolar cell responses, reducing OFF-bipolar cell responses and quickening both OFF-bipolar and photoreceptor responses. High BPA exposure was also associated with the lowest positive OMRs in adults. For both A and B, the timeline at the top indicates exposure age (yellow box) and when assessments were made (3–4 months of age).