31 research outputs found

    Plasticizers as endocrine disruptors: the case of the endocannabinoid system in teleost species

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    Plasticizers, as Bisphenol A (BPA) and Di-isononyl phthalate (DiNP), are chemicals added to the plastics to improve their performance, which recently, turned into a ubiquitous in the environment due to the high rate of use and manufacture of plastic, and hence, of the plasticizers. BPA and DiNP have been found in all environmental matrices, being bioavailable for organisms and reported as endocrine-disrupting chemicals (EDCs). On the other hand, the endocannabinoid system (ECS), a novel lipid signaling system lately defined, has been proposed as a new target for the potential effects of the EDCs. The ECS has been described in several species and it has an essential role for the well-being of the organisms. For that, the main goal of the present project was to assess the effects of BPA and DiNP in the ECS of Danio rerio and Sparus aurata. To accomplish this objective D. rerio and S. aurata were chronically treated (3 weeks) with BPA and DiNP, separately, via water or via food respectively. Generally, the results for both species, showed a deregulation of the ECS at central (brain) and peripheral level (liver and gonads) at mRNA and protein level, the alteration of the hepatic lipid metabolism and the biochemical composition of liver in both species. In the gonads, the reproductive performance measured as fertility rate, the gonadal morphology and sexual hormone levels were also altered by the treatments of both pollutants. In conclusion, the chronic exposure to environmental concentrations of BPA and DiNP induced alterations at the ECS pathway in Danio rerio and Sparus aurata. Finally, the ECS can be considered as new target for EDCs such as BPA and DiNP

    Endocrine-disrupting chemicals in aquatic environment: what are the risks for fish gametes?

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    Over the past 25 years, extensive research in vertebrate species has identified several genomic pathways altered by exposures to anthropogenic chemicals with hormone-like activity mediated by their interaction with nuclear receptors. In addition, many pollutants have been shown to interfere with non-genomic (non-classical) pathways, but this mechanism of endocrine disruption is still poorly understood. Recently, the number of publications describing the effects of Endocrine disrupting chemicals (EDCs) on fish reproduction, focusing on the deregulation of the hypothalamus-pituitary-gonadal axis as well as on gamete quality, significantly increased. Depending on their ability to mimic endogenous hormones, the may differently affect male or female reproductive physiology. Inhibition of gametogenesis, development of intersex gonads, alteration of the gonadosomatic index, and decreased fertility rate have been largely documented. In males, alterations of sperm density, motility, and fertility have been observed in several wild species. Similar detrimental effects were described in females, including negative outcomes on oocyte growth and maturation plus the occurrence of apoptotic/autophagic processes. These pathways may affect gamete viability considered as one of the major indicators of reproductive endocrine disruption. Pollutants act also at DNA level producing DNA mutations and changes in epigenetic pathways inducing specific mechanisms of toxicity and/or aberrant cellular responses that may affect subsequent generation(s) through the germline. In conclusion, this review summarizes the effects caused by EDC exposure on fish reproduction, focusing on gametogenesis, giving a general overview of the different aspects dealing with this issue, from morphological alteration, deregulation of steroidogenesis, hormonal synthesis, and occurrence of epigenetic process

    Effects of diisononyl phthalate on Danio rerio reproduction

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    Di-isononyl phthalate (DiNP) is a high molecular weight phthalate commonly used as a plasticizer. It was introduced as a replacement for bis (2-ethylhexyl) phthalate (DEHP) which is used in the production of plasticized polyvinyl chloride (PVC). The purpose of this study was to investigate for the first time the effect of DiNP on female reproductive physiology in Danio rerio. Fish were exposed to five different doses of DiNP plus control (0 μg/L; 0.42 μg/L; 4.2 μg/L; 42 μg/L; 420 μg/L; 4200 μg/L) for a period of 21 days. We evaluated fish fecundity, oocyte growth, autophagic and apoptotic processes, as well as changes in morphological and biochemical composition of oocytes, using, qPCR analysis, histology and Fourier transform infrared imaging. The results demonstrate a non-monotonic dose response to DiNP. Greater differences were observed at the lowest (0.42 μg/L) and higher concentrations (420 μg/L; 4200 μg/L) of DiNP. The findings provide evidence that exposure to DiNP adversely affect oocytes growth and maturation, leading to abnormal gonadal development and reproduction in zebrafish

    Effects of BPA on zebrafish gonads: Focus on the endocannabinoid system

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    Bisphenol A (BPA), a monomer used for polycarbonate manufacture, has been widely reported as an endocrine-disrupting chemical (EDC). Among other alterations, BPA induces reproductive dysfunctionalities. Changes in the endocannabinoid system (ECS) have been recently shown to be associated with reproductive disorders. The ECS is a lipid-based signaling system (cannabinoid receptors, endocannabinoids and enzymatic machinery) involved in several physiological functions. The main goal of the present study was to assess the effects of two environmental concentrations of BPA (10 and 20 μg/L) on the ECS in 1-year old zebrafish gonads. In males, BPA increased the gonadosomatic index (GSI) and altered testicular levels of endocannabinoids as well as reduced the testicular area occupied by spermatogonia. In male liver, exposure to 20 μg/L BPA significantly increased vitellogenin (vtg) transcript levels. In female zebrafish, BPA altered ovarian endocannabinoid levels, elevated hepatic vtg mRNA levels as well as increased the percentage of vitellogenic oocytes in the ovaries. In conclusion, exposure to two environmentally relevant concentrations of BPA altered the ECS and consequently, gonadal function in both male and female zebrafish

    Endocannabinoid System and Metabolism: The Influences of Sex

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    The endocannabinoid system (ECS) is a lipid signaling system involved in numerous physiological processes, such as endocrine homeostasis, appetite control, energy balance, and metabolism. The ECS comprises endocannabinoids, their cognate receptors, and the enzymatic machinery that tightly regulates their levels within tissues. This system has been identified in various organs, including the brain and liver, in multiple mammalian and non-mammalian species. However, information regarding the sex-specific regulation of the ECS remains limited, even though increasing evidence suggests that interactions between sex steroid hormones and the ECS may ultimately modulate hepatic metabolism and energy homeostasis. Within this framework, we will review the sexual dimorphism of the ECS in various animal models, providing evidence of the crosstalk between endocannabinoids and sex hormones via different metabolic pathways. Additionally, we will underscore the importance of understanding how endocrine-disrupting chemicals and exogenous cannabinoids influence ECS-dependent metabolic pathways in a sex-specific manner

    Zebrafish exposed to a cocktail of pesticides during early development display long-lasting neurobehavioral alterations

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    15 pages, 6 figures, supplementary information https://doi.org/10.1007/s00204-025-04129-6.-- Data availability: Coding generated for this manuscript and additional information are available within Supplementary Material [see Supplementary Information (SI)]. Raw data can be kindly requested to corresponding authorsThe widespread use of pesticides is increasing the presence of environmental contaminants with potential impacts on biodiversity, ecosystems, and human health. Although long-term pesticide effects have been previously studied, the long-term impact of an acute pesticide exposure during critical early developmental periods remains poorly understood. Here, we used zebrafish to examine whether acute exposure to a pesticide mixture at 0.5 μg/L (the maximum allowed in drinking water) during the first 5 days post-fertilisation (dpf) of development has lasting effects at 28 dpf. Zebrafish were assessed behaviourally, morphologically, and molecularly both immediately after exposure at 5 dpf and later at 28 dpf. Our results show alterations in stress-response that start to emerge right after the developmental exposure and are associated with a less anxious-like phenotype at juvenile stages. Interestingly, despite the observed behavioural phenotype at 28 dpf, it did not lead to significant molecular changes in the hypothalamic-pituitary-interrenal (HPI) axis at this stage. On the contrary, a positive control group of juvenile fish subjected to a sustained pesticide exposure throughout the 28 dpf showed both reduced anxiety-like behaviour and HPI alterations. Our study suggests that even an acute exposure to a low-concentration of pesticides during critical developmental periods can result in enduring behavioural changesOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Montpellier Université d'Excellence,MUSE-Pestifish 2017, Nicola Marchi, HORIZON EUROPE Marie Sklodowska-Curie Actions, 101153110, Isabel Forner-Piquer, ANSES-OptoFish, ANSES-OptoFish, Nicola Marchi, National Institute of Health, NIH U01 DA044400-03, Caroline H. Brennan, Ministerio de Ciencia, Innovación y Universidades, RYC2021-034012-I, Jose Vicente Torres-Perez, British Pharmacological Society, 2023 Pickford Award, Jose Vicente Torres-PerezIFP was supported by MUSE-Pestifish 2017 (Programme for Excellence of the University of Montpellier 2017 to NM), IFP also received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant (agreement No 101153110). NM is supported by an ANSES-OptoFish. CHB is supported by National Institute of Health (NIH U01 DA044400-03). JVTP is funded by the Spanish Ministry of Science, Innovation and Universities (MCIN/AEI/https://doi.org/10.13039/501100011033) and the European Union “NextGenerationEU”/PRTR with a Ramón y Cajal contract (Grant RYC2021-034012-I); JVTP is also supported by the 2023 Pickford Award from the British Pharmacological SocietyThis work contributes to the Institut de Ciències del Mar "Severo Ochoa Centre of Excellence" accreditation CEX2024-001494-S funded by AEI 10.13039/501100011033 of the Spanish Ministry of Science and InnovationPeer reviewe
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