Bisphenol A analogues induce a feed-forward estrogenic response in zebrafish

Area of Science:

• Environmental Toxicology
• Endocrinology
• Molecular Biology

Background:

• Bisphenol A (BPA) exposure is linked to adverse health effects in humans and wildlife.
• BPA analogues are synthesized as potential replacements, necessitating evaluation of their endocrine-disrupting potential.
• Understanding the estrogenic activity of BPA and its analogues is crucial for risk assessment.

Purpose of the Study:

• To assess the estrogenic activity of BPA and five analogues (BPAF, BPE, BPC, BPC-Cl, BPS) using zebrafish models.
• To compare in vivo and in vitro estrogenic responses across different bisphenol compounds.
• To identify potential biomarkers for estrogenicity in zebrafish larvae.

Main Methods:

• Utilized transgenic estrogen reporter (5xERE:GFP) zebrafish for in vivo assessment of agonistic effects.
• Employed reporter cells expressing zebrafish estrogen receptors for in vitro estrogenicity testing.
• Conducted quantitative PCR to analyze the expression of estrogen target genes (vtg1, esr1, cyp19a1b, f13a1a).

Main Results:

• BPA, BPAF, BPE, and BPC induced GFP expression in zebrafish reporter fish, primarily in heart valves and liver.
• BPC-Cl activated GFP expression mainly in the liver, while BPS showed minimal activity.
• In vitro assays revealed differential activation of zebrafish estrogen receptors (Esr1 and Esr2a) by the tested compounds.
• The f13a1a gene was strongly activated by all tested bisphenols, suggesting its utility as a biomarker.
• Exposure to BPAF and BPC-Cl increased estradiol (E2) levels in zebrafish larvae.

Conclusions:

• BPA and its analogues exhibit varying degrees of estrogenic activity in zebrafish.
• The f13a1a mRNA is a promising biomarker for detecting estrogenicity in larval fish.
• Observed increases in E2 levels suggest a feed-forward mechanism amplifying estrogenic effects.