Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an “obesogenic” phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.

The rise of obesity in humans is a major health concern of our times, affecting an increasing proportion of the population worldwide. It is now evident that this phenomenon is not only associated with the lack of exercise and a balanced diet, but also due to environmental factors, such as exposure to environmental chemicals that interfere with lipid homeostasis. These chemicals, also known as obesogens, are present in a wide range of products of our daily life, such as cosmetics, paints, plastics, food cans and pesticide-treated food, among others. A growing body of evidences indicates that their action is not limited to mammals. Obesogens also end up in the aquatic environment, potentially affecting its ecosystems. In fact, reports show that some environmental chemicals are able to alter lipid homeostasis, impacting weight, lipid profile, signaling pathways and/or protein activity, of several taxa of aquatic animals. Such perturbations may give rise to physiological disorders and disease. Although largely unexplored from a comparative perspective, the key molecular components implicated in lipid homeostasis have likely appeared early in animal evolution. Therefore, it is not surprising that the obesogen effects are found in other animal groups beyond mammals. Collectively, data indicates that suspected obesogens impact lipid metabolism across phyla that have diverged over 600 million years ago. Thus, a consistent link between environmental chemical exposure and the obesity epidemic has emerged. This review aims to summarize the available information on the effects of putative obesogens in aquatic organisms, considering the similarities and differences of lipid homeostasis pathways among metazoans, thus contributing to a better understanding of the etiology of obesity in human populations. Finally, we identify the knowledge gaps in this field and we set future research priorities.

In this study, the effects of two environmental endocrine disruptors, the synthetic pharmaceutical estrogen (ethynylestradiol, EE2) and antifoulant (tributyltin, TBT) representing two different modes of action on the endocrine system, were studied on brain steroidogenic pathway of juvenile Atlantic salmon (Salmo salar). Neurosteroidogenesis was studied using brain aromatase gene isoforms and enzyme activity, in parallel with typical xenoestrogen responses, such as brain estrogen receptor (ERalpha) and plasma vitellogenin (Vtg) levels. Fish were exposed to nominal waterborne EE2 (5 and 50 ng/l) and TBT (50 and 250 ng/l) concentrations dissolved in dimethyl sulfoxide (DMSO), singly and in combination. Gene expressions were quantified using real-time PCR with gene-specific primers, aromatase activity was analyzed using the tritiated water-release assay, and plasma Vtg was analyzed using competitive ELISA. Our data show that EE2 induced a concentration-specific modulation of P450aromA, P450aromB, and aromatase activity in addition to ERalpha and plasma Vtg levels in juvenile salmon at day 3 postexposure. TBT exposure caused both the elevation and inhibition of P450aromA, P450aromB, and aromatase activity levels, depending on concentration, at day 7 postexposure. TBT elevated and inhibited ERalpha and plasma Vtg and also antagonized EE2-induced expression of the studied variables at day 7 postexposure. Interestingly, the carrier vehicle DMSO modulated the receptor-mediated and non-receptor-mediated estrogenic responses at day 7 postexposure, compared to day 3. In general, these findings suggest that the exposed animals are experiencing impaired steroidogenesis and modulations of receptor-mediated endocrine responses. Given the integral role of neurosteroids in homeostatic process, growth, metabolism, reproduction, and development of central nervous system and function, these effects may have serious impact on this endocrine pathway and potentially affect organismal reproductive performance and health. In conclusion, the regulation of steroidogenesis is a fundamental mechanism involved in the biosynthesis of important biological compounds, irrespective of organ; therefore, the search for the molecular targets of xenoestrogens, given singly and also in combination, in these pathways will increase our understanding of organismal endocrine disruption and potential consequences.

The regulation of pesticides in the European Union (EU) relies on a network of hard law (legislation and implementing acts) and soft law (non-legally binding guidance documents and administrative and scientific practices). Both hard and soft laws govern how risk assessments are conducted, but a significant role is left to the latter. Europe’s pesticide regulation is one of the most stringent in the world. Its stated objectives are to ensure an independent, objective and transparent assessment of pesticides and achieve a high level of protection for health and environment. However, a growing body of evidence shows that pesticides that have passed through this process and are authorised for use may harm humans, animals and the environment. The authors of the current paper – experts in toxicology, law and policy – identified shortcomings in the authorisation process, focusing on the EU assessment of the pesticide active substance glyphosate. The shortcomings mostly consist of failures to implement the hard or soft laws. But in some instances the law itself is responsible, as some provisions can only fail to achieve its objectives. Ways to improve the system are proposed, requiring changes in hard and soft laws as well as in administrative and scientific practices.

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