Endocrine Abstracts

The harmful impact of exposure to ultraviolet (UV) filters is a topic of widespread concern due to human toxicological effects. Exposure to these environmental contaminants has emerged due to their extensive use as ingredients in personal care products and their incomplete removal in wastewater treatment plants. Due to their lipophilicity, UV filters are prone to bioaccumulate in aquatic biota, presenting potential adverse effects on both aquatic organisms and humans. The octinoxate (OMC) is one of the most used UV filters as ingredient in the cosmetic industry. Currently, OMC is included in the Community rolling action plan (CoRAP) list (REACH) and List II (EC/List No. 629-661-9) of substances under evaluation for endocrine-disrupting properties under EU legislation. It is known that OMC is an endocrine-disrupting compound (EDC), which interacts with the Hypothalamus-Pituitary-Thyroid (HPT)-axis. Despite this, the toxicological effects induced by OMC on the thyroid hormone (TH) system are not completely understood. Zebrafish (Danio rerio: Cyprinidae, Teleostei) is one of the most widely used model species in developmental biology and biomedicine for endocrine disruption prediction studies. Several studies have reported the crucial role of TH in normal development and physiological homeostasis during the life cycle of zebrafish, including morphogenesis, neurodevelopment, pigmentation, metabolism, and growth. Due to the highly conserved HPT-axis with humans, zebrafish is a promising alternative model for mechanistic studies of TH regulation. Furthermore, zebrafish embryos can be used as a non-animal alternative up to 5-days post fertilization (dpf) (Directive 2010/63/EU, 2010). In this context, this work aimed to understand if and how the exposure to UV-filter OMC modifies the response to exogenous triiodothyronine (T3) and impairs normal zebrafish embryo development. To achieve this, an integrative approach from apical to transcriptional endpoints was used. Zebrafish embryos were exposed to sub-lethal concentrations of OMC (0.04 – 4 mg/l) during 120 hours in binary mixture with T3 (0.02 mg/l). The endpoints evaluated included fish embryo development (hatching and malformations), heart rate, and behaviour. Moreover, the expression of a suite of genes involved in the HPT axis were also assessed as transcriptional endpoint. By unveiling the thyroid-disrupting effects of OMC in zebrafish-developing embryos, we will contribute to increase the knowledge of the OMC mode of action in order to develop measures to promote human thyroid health.