Ethinylestradiol (EE2) residues from birth control pills impair nervous system development and swimming behavior of zebrafish larvae

The ubiquitous use of ethinylestradiol (EE2), an active constituent of birth control preparations, results in continuous release of this synthetic estrogen to surface waters. Many studies document the untoward effects of EE2 on the endocrine system of aquatic organisms. Effects of environmental EE2 on the nervous system are still poorly documented. We studied effects of pico- to nanomolar concentrations of EE2 on early nervous system development of zebrafish larvae. EE2 disrupted axonal nerve regeneration and hair cell regeneration up to 50%. Gene expression in larval brain tissues showed significantly upregulated expression of target genes, such as estrogen and progesterone receptors, and aromatase B. In contrast, downregulation of the tyrosine hydroxylase, involved in the synthesis of neurotransmitters, occurred concomitant with diminution of proliferating cells. Overall, the size of exposed fish larvae decreased by 25% and their swimming behavior was modified compared to non-treated larvae. EE2 interferes with nervous system development, both centrally and peripherally, with negative effects on regeneration and swimming behavior. Survival of fish and other aquatic species may be at risk in chronically EE2-contaminated environments. [Display omitted] •EE2 disrupts the axonal nerve regeneration of the lateral line of zebrafish larvae.•EE2 alters hair cell regeneration in the peripheral nervous system.•EE2 alters gene expression and cells in proliferation in the central nervous system.•EE2 leads to the reduction of zebrafish larvae size.•EE2 modify swimming behavior of zebrafish larvae.