Long-term molecular effects of developmental estrogen signaling manipulation in the zebrafish retina

<p>The steroid hormone estradiol (E2), the biologically relevant estrogen, plays a crucial role in visual system development and maintenance. We hypothesized that manipulation to E2 signaling during critical periods of visual system development would cause long-term changes in the expression and activation of E2 transcriptional and intracellular targets in the adult zebrafish retina. Zebrafish larvae (72hpf and 7dpf) and adults were transiently exposed to two environmentally relevant concentrations of bisphenol A (BPA), an estrogen mimic and ubiquitous environmental chemical, and the long-term impacts of developmental exposure were compared to immediate effects in adults. RT-qPCR and Western blotting techniques were used to assess changes in gene expression of neural aromatase (AroB) and estrogen receptors (ERs) and the activation of E2-initiated MAPK and PI3K/Akt signaling cascades in retina of adults, respectively. Exposure to low BPA concentrations (0.001μM), but not high (0.1μM), at 72hpf significantly increased AroB and decreased ERβ gene expression, increased ERβ expression at 7dpf, and had no significant effect at adulthood. Phosphorylation of Akt and MAPKs ERK and JNK was also exposure age-dependent, where BPA at 72hpf decreased phosphorylation of Akt and ERK but increased JNK phosphorylation at 7dpf. Results were compared in brain, which further revealed concentration and exposure-age dependent effects of developmental BPA exposure. Further, the patterns of BPA-induced E2 pathway dysregulation in retina were unique to those in brain, highlighting the significance of studies examining E2 signaling in retina.</p>