Pancreatic Beta Cells Are a Sensitive Target of Embryonic Exposure to Butylparaben in Zebrafish (Danio Rerio)

Background: Butylparaben (butyl p-hydroxybenzoic acid) is a common cosmetic and pharmaceutical preservative reported to induce oxidative stress and endocrine disruption. Embryonic development is sensitive to oxidative stress, with redox potentials playing critical roles in progenitor cell fate decisions. Because pancreatic beta cells have been reported to have low antioxidant gene expression, they may be sensitive targets of oxidative stress. We tested the hypotheses that butylparaben causes oxidative stress in the developing embryo, and that pancreatic beta cells are a sensitive target of butylparaben embryotoxicity.

Methods: Transgenic insulin:GFP zebrafish embryos (Danio rerio) were treated daily with 0, 250, 500, 1,000, and 3,000 nM butylparaben. Pancreatic islet and whole embryo development were examined though 7 days postfertilization, and gene expression was measured by quantitative real-time PCR. Glutathione (GSH) and cysteine redox content were measured at 28 hr postfertilization using HPLC.

Results: Butylparaben exposure caused intestinal effusion, pericardial edema, and accelerated yolk utilization. At 250 nM, beta cell area increased by as much as 55%, and increased incidence of two aberrant morphologies were observed-fragmentation of the islet cluster and ectopic beta cells. Butylparaben concentrations of 500 and 1,000 nM increased GSH by 10 and 40%, respectively. Butylparaben exposure downregulated transcription factor pdx1, as well as genes involved in GSH synthesis, while upregulating GSH-disulfide reductase (gsr).

Conclusions: The endocrine pancreas is a sensitive target of embryonic exposure to butylparaben, which also causes developmental deformities and perturbs redox conditions in the embryo.