Proteomic profile of the effects of low-dose bisphenol A on zebrafish ovaries

• Published in: Food and chemical toxicology 2021-10, Vol.156, p.112435, Article 112435
• Main Authors: Molina, Ana M., Abril, Nieves, Lora, Antonio J., Huertas-Abril, Paula V., Ayala, Nahum, Blanco, Carmen, Moyano, M.Rosario
• Format: Article
• Language: English
• Subjects: Animals; Benzhydryl Compounds - administration & dosage; Benzhydryl Compounds - toxicity; Bisphenol-A; DNA Methylation - drug effects; Dose-Response Relationship, Drug; Female; Ovary; Ovary - drug effects; Ovary - metabolism; Oxidative Stress - drug effects; Phenols - administration & dosage; Phenols - toxicity; Proteomic; Proteomics - methods; Proteostasis; Proteostasis - drug effects; Zebrafish
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2021.112435

Human exposure to bisphenol-A (BPA) is largely unavoidable because BPA is an environmental contaminant found in soil, water, food and indoor dust. The safety of authorized BPA amounts in consumer products is under question because new studies have reported adverse effects of BPA at doses far below that previously established by the NOAEL (50 μg/kg per day). To protect public health, the consequences of low-dose BPA exposure in different organs and organismal functions must be further studied to generate relevant data. This study attempted to investigate the effects and potential molecular mechanisms of short-term exposure to 1 μg/L BPA on zebrafish ovarian follicular development. We observed only minor changes at the histopathological level with a small (3 %) increase in follicular atresia. However, a shotgun proteomics approach indicated deep alterations in BPA-exposed ovarian cells, including induction of the oxidative stress response, metabolic shifts and degradome perturbations, which could drive oocytes towards premature maturation. Based on these results, it could be suggested that inadvertent exposure to small concentrations of BPA on a continuous basis causes alteration in biological processes that are essential for healthy reproduction. [Display omitted] •Exposure to 1 μg/L BPA activates the NRF2-mediated oxidative stress response in zebrafish ovaries.•Changes in the one-carbon metabolism pathway might alter DNA methylation patterns.•Ovarian cells prevent damage by promoting GSH and NADPH availability.•Cholesterol trafficking results may have affected and hindered steroid synthesis.•Low-dose BPA alters proteostasis and may promote follicle maturation and atresia.