Abstract
Purpose :
We previously reported that developmental manipulation to estradiol (E2) signaling causes long-term visual deficits in adult zebrafish. Here, we hypothesize that developmental exposure to environmentally relevant concentrations of bisphenol-A (BPA), an estrogen mimic, will cause long-term molecular changes in E2 signaling components within retina, including expression of estrogen receptors (ERs) and neural aromatase (cyp19a1b), similar to what has been well-established in the brain.
Methods :
Zebrafish larvae and adults were transiently exposed to either low BPA (0.001μM), high BPA (0.1μM), vehicle control (DMSO, 0.003%), or water for 24 hours. Larval fish were returned to control conditions and reared until adulthood; adults were immediately sacrificed after exposure. Total RNA was extracted from adult retina and brain (N=2-3/treatment) and used in quantitative reverse transcription PCR (RT-qPCR) to quantify changes in mRNA expression of E2 transcriptional targets. Relative gene expression was determined with the comparative Ct method (2-ΔΔCt).
Results :
Preliminary results show upregulation of cyp19a1b and ERβ mRNA in retina and brain of adults exposed to BPA. Upregulation was concentration dependent in retina whereas low BPA caused the greatest expression in brain tissue, and at a greater overall relative expression than in retina (~300%). Adults developmentally exposed to low BPA, but not high BPA, exhibited upregulation of cyp19a1b (~600%) and ERα (250%) in retina; changes in ERβ expression were not detected in retina at either concentration. Larval exposures did not alter the expression of adult brain ERs or cyp19a1b.
Conclusions :
Our results suggest that developmental disruption to E2 signaling through BPA exposure can have long-term molecular effects in retinal tissue. These differences were also observed in adults acutely exposed, suggesting that the effects of BPA both occur rapidly and sustain. The tissue-dependent differences observed suggest that retinal E2 signaling and regulation is unique to mechanisms well-studied in the brain, highlighting the significance of retinal-specific research on estrogenic pathways and the effects of disruption.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.