Plant Protection Products, more commonly referred to as pesticides and biocides, are used to control a wide range of yield-reducing pests including insects, fungi, nematodes, and weeds. Concern has ...been raised that some pesticides may act as endocrine disrupting chemicals (EDCs) with the potential to interfere with the hormone systems of non-target invertebrates and vertebrates, including humans. EDCs act at low doses and particularly vulnerable periods of exposure include pre- and perinatal development. Of critical concern is the number of pesticides with the potential to interfere with the developing nervous system and brain, notably with thyroid hormone signaling. Across vertebrates, thyroid hormone orchestrates metamorphosis, brain development, and metabolism. Pesticide action on thyroid homeostasis can involve interference with TH production and its control, displacement from distributor proteins and liver metabolism. Here we focused on thyroid endpoints for each of the different classes of pesticides reviewing epidemiological and experimental studies carried out both in
and
. We conclude first, that many pesticides were placed on the market with insufficient testing, other than acute or chronic toxicity, and second, that thyroid-specific endpoints for neurodevelopmental effects and mixture assessment are largely absent from regulatory directives.
Thyroid hormones (THs) play critical roles in profound changes in many vertebrates, notably in mammalian neurodevelopment, although the precise molecular mechanisms of these fundamental biological ...processes are still being unravelled. Environmental and health concerns prompted the development of chemical safety testing and, in the context of endocrine disruption, identification of thyroid hormone axis disrupting chemicals (THADCs) remains particularly challenging. As various molecules are known to interfere with different levels of TH signalling, screening tests for THADCs may not rely solely on in vitro ligand/receptor binding to TH receptors. Therefore, alternatives to mammalian in vivo assays featuring TH-related endpoints that are more sensitive than circulatory THs and more rapid than thyroid histopathology are needed to fulfil the ambition of higher throughput screening of the myriad of environmental chemicals. After a detailed introduction of the context, we have listed current assays and parameters to assess thyroid disruption following a literature search of recent publications referring to non-mammalian models. Potential THADCs were mostly investigated in zebrafish and the frog Xenopus laevis, an amphibian model extensively used to study TH signalling.
•Testing for thyroid hormone (TH) disruptors is particularly challenging due to the lack of validated in vitro assays.•In contrast to rodent models, amphibian and teleost embryos or larvae are amenable to higher throughput screening.•Xenopus laevis is employed in several validated and standardized assays to investigate the effects of TH axis disrupting chemicals.•The zebrafish (Danio rerio) is a promising alternative vertebrate model to examine disruption of TH signalling.•Further studies are needed to implement neurodevelopmental and behavioural endpoints mediated by TH signalling.
•Concerns about microplastic pollution in aquatic environment is recent.•Sampling to monitor microplastic pollution temporal dynamic are sporadic and recent.•Natural History Collection time series ...are useful for biota microplastic monitoring.•Natural History Collection have specificities to reckon with to perform such studies.•Bioindicator species can be determined from Natural History Collections specimens.
Microplastic pollution has risen to such a level that concerns are being raised regarding its consequences on the environment, especially the marine environment. Understanding microplastic pollution temporal dynamics is critical but requires time-series. However, concerns about microplastic pollution being recent, long term monitoring programs have only started very recently and remain scarce. Natural History Collections that represent archives from the past can constitute time-series. Although underused, they have evinced their success to study various stressors including pollutants, in particular when using bioindicators. Bioindicator species should be defined with regards to the studied environmental disturbance according to established criteria. Those criteria include occurring frequently, being sensitive to the pollutant, and allowing, via their monitoring, a summary of the pollutant’s impacts at molecular, organismal or population levels. However, to analyse bioindicator species in Natural History Collection time-series, several specificities need to be considered. Starting from a review of articles that utilised such collections to study microplastic evolution in a given ecosystem, and focusing on their methodologies, we emphasise Natural History Collection features that need to be taken into account when choosing the most adequate taxon and extraction techniques. In particular we discuss four collection features: sampling heterogeneity, taxonomic misidentification, past environmental contamination and specimen destruction and provide leads to address these issues. We believe that combining the concept of bioindicator with valuable samples from Natural History Collections is of particular interest to monitor past microplastic pollution and better predict future trends. This constitutes a necessary step in assessing the basal level and the continuing evolution of this ever-increasing pollution.
•We transiently exposed pregnant mice to 2 and 200 µg bisphenol F/kg/day from E15-P21.•Both doses did not alter serum thyroid hormone levels at P15, P21 and P60.•RNA-seq showed dysregulated ...neurodevelopmental genes in the P15 subventricular zone.•The highest dose permanently decreased SVZ-neurogenesis but not oligodendrogenesis at P60.•P60 mice perinatally exposed to the highest BPF dose memorized odours less well.
Neural stem cells in the murine subventricular zone (SVZ) reactivate during postnatal development to generate neurons and glia throughout adulthood. We previously demonstrated that a postnatal thyroid hormone (TH) peak orchestrates this remodelling, rendering this process vulnerable to endocrine disruption. We exposed mice to 2 or 200 µg/kg bw/day of the bisphenol A-replacement and suspected TH-disruptor bisphenol F (BPF) in the drinking water, from embryonic day 15 to postnatal day 21 (P21). In parallel, one group was exposed to the TH-synthesis blocker propylthiouracil (0.15 % PTU). In contrast to PTU, BPF exposure did not affect serum TH levels at P15, P21 or P60. RNA-seq on dissected SVZs at P15 revealed dysregulated neurodevelopmental genes in all treatments, although few overlapped amongst the conditions. We then investigated the phenotype at P60 to analyse long-term consequences of transient developmental exposure. As opposed to hypothyroid conditions, and despite dysregulated oligodendrogenesis-promoting genes in the P15 SVZ exposed to the highest dose of BPF, immunostainings for myelin and OLIG2/CC1 showed no impact on global myelin content nor oligodendrocyte maturation in the P60 corpus callosum, apart from a reduced thickness. The highest dose did reduce numbers of newly generated SVZ-neuroblasts with 22 %. Related to this were behavioural alterations. P60 mice previously exposed to the highest BPF dose memorized an odour less well than control animals did, although they performed better than PTU-exposed animals. All mice could discriminate new odours, but all exposed groups showed less interest in social odours. Our data indicate that perinatal exposure to low doses of BPF disrupts postnatal murine SVZ remodelling, and lowers the adult neuron/oligodendroglia output, even after exposure had been absent for 40 days. These anomalies warrant further investigation on the potential harm of alternative bisphenol compounds for human foetal brain development.
This review covers recent findings on the main categories of thyroid hormone–disrupting chemicals and their effects on brain development. We draw mostly on epidemiological and experimental data ...published in the last decade. For each chemical class considered, we deal with not only the thyroid hormone–disrupting effects but also briefly mention the main mechanisms by which the same chemicals could modify estrogen and/or androgen signalling, thereby exacerbating adverse effects on endocrine-dependent developmental programmes. Further, we emphasize recent data showing how maternal thyroid hormone signalling during early pregnancy affects not only offspring IQ, but also neurodevelopmental disease risk. These recent findings add to established knowledge on the crucial importance of iodine and thyroid hormone for optimal brain development. We propose that prenatal exposure to mixtures of thyroid hormone–disrupting chemicals provides a plausible biological mechanism contributing to current increases in the incidence of neurodevelopmental disease and IQ loss.
With an increasing collective awareness of the rapid environmental changes, questions and theories regarding the adaptability of organisms are emerging. Global warming as well as chemical and ...non-chemical pollution have been identified as triggers of these adaptative changes, but can we link different kinds of stressors to certain phenotypic traits? The physiological adaptation, and particularly endocrine system adaptation, of living beings to urban environments is a fascinating way of studying urban endocrinology, which has emerged as a research field in 2007. In this paper, we stress how endocrine disruption in humans and environment can be studied in the urban environment by measuring the levels of pollution, endocrine activities or adversity. We broaden the focus to include not only exposure to the chemicals that have invaded our private spheres and their effects on wild and domestic species but also non-chemical effectors such as light, noise and climate change. We argue that taking into account the various urban stress factors and their effects on the endocrine system would enable the adoption of new approaches to protect living organisms.
•Urban settings pose challenges for humans and animals. They share the same environment and can serve as sentinels.•Challenges in urban environments include pollution, artificial light, electromagnetic waves, noise, climate change, sedentary lifestyle, lack of nature, and endocrine effects.•The endocrine system is vital for organisms' adaptation to their surroundings and has remained consistent throughout evolution.•Considering urban stressors' impact on the endocrine system can lead to new approaches for protecting living organisms.•Comprehensive studies should integrate multiple levels of information and adopt a translational, holistic "One Health" perspective.
Reference genes are essential for gene expression analysis when using real-time quantitative PCR (RT-qPCR). Xenopus laevis is a popular amphibian model for studying vertebrate embryogenesis and ...development. Further, X. laevis is ideal for studying thyroid signaling due to its thyroid dependent metamorphosis, a stage comparable to birth in humans. When using PCR based studies, a primary concern is the choice of reference genes. Commonly used references are eef1a1, odc1, rpl8, and actnB, although there is a lack of ad hoc reference genes for X. laevis. Here, we used previously published RNA-seq data on different X. laevis stages and identified the top 14 candidate genes with respect to their expression levels as a function of developmental stage and degree of variation. We further evaluated the stability of these and other candidate genes using RT-qPCR on various stages including the unfertilised eggs, whole embryos during early development and brains during late development. We used four different statistical software packages: deltaCT, geNorm, NormFinder and BestKeeper. We report optimized reference gene pair combinations for studying development (early whole embryos), brains at later stages (metamorphosis and adult), and thyroid signalling. These reference gene pairs are suitable for studying different aspects of X. laevis development and organogenesis.
Pyrethroid metabolites are widely detectable in urine from the general population, including pregnant women and children. Pyrethroids are neurotoxic and suggested endocrine disruptors. Exposure ...during vulnerable developmental time windows may have long-term impacts on neurodevelopment.
To evaluate the epidemiological evidence for neurodevelopmental effects related to prenatal and childhood pyrethroid exposure in a systematic review and to assess biological plausibility by evaluating mechanistic evidence.
We searched PubMed and Web of Science up to September 1, 2021 and included original studies published in English in which pyrethroid exposure was measured or estimated during pregnancy or childhood and associations with neurodevelopmental outcomes in the children were investigated. The Navigation Guide Systematic Review Methodology was used to evaluate the epidemiological evidence. For mechanistic evidence, we focused on relevant key events (KEs) suggested in Adverse Outcome Pathways (AOPs) using the OECD-supported AOP-wiki platform. A systematic search combining the KEs with pyrethroids, including 26 individual compounds, was performed in the ToxCast database.
Twenty-five epidemiological studies met the inclusion criteria, 17 presented findings on prenatal exposure, 10 on childhood exposure and two on both exposure windows. The overall body of evidence was rated as “moderate quality” with “sufficient evidence” for an association between prenatal pyrethroid exposure and adverse neurodevelopment. For childhood exposure, the overall rating was “low quality” with “limited evidence” because of cross-sectional study design. Regarding mechanistic evidence, we found that pyrethroids are able to interfere with neurodevelopmental KEs included in established AOPs for adverse neurodevelopmental. The evidence was strongest for interference with thyroid hormone (TH) function.
Pyrethroids are probably human developmental neurotoxicants and adverse impacts of pyrethroid exposure on neurodevelopment are likely at exposure levels occurring in the general population. Preventive measures to reduce exposure among pregnant women and children are warranted.
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•Studies in humans and experimental animals have evidenced thyroid system disruption by lithium.•Lithium has neurodevelopmental effects on animals.•Lithium fulfils the WHO’s ...definition of a thyroid system disruptor.•The increasing use of lithium in industry raises health concerns.
Lithium is a key medication for the treatment of psychiatric disorders and is also used in various industrial applications (including battery production and recycling). Here, we review published data on the endocrine-disrupting potential of lithium, with a particular focus on the thyroid hormone system. To this end, we used PubMed and Scopus databases to search for, select and review primary research addressing human and animal health endpoints during or after lithium exposure at non-teratogenic doses. Given the key role of thyroid hormones in neurodevelopmental processes, we focused at studies of the neural effects of developmental exposure to lithium in humans and animals. Our results show that lithium meets the World Health Organization’s definition of a thyroid hormone system disruptor – particularly when used at therapeutic doses. When combined with knowledge of adverse outcome pathways linking molecular initiating events targeting thyroid function and neurodevelopmental outcomes, the neurodevelopmental data reported in animal experiments prompt us to suggest that lithium influences neurodevelopment. However, we cannot rule out the involvement of additional modes of action (i.e. unrelated to the thyroid hormone system) in the described neural effects.
Given the increasing use of lithium salts in new technologies, attention must be paid to this emerging pollutant – particularly with regard to its potential effects at environmental doses on the thyroid hormone system and potential consequences on the developing nervous system.
Pesticides are used worldwide with potential harmful effects on both fauna and flora. The Kibale National Park in Uganda, a site renowned for its biodiversity is surrounded by tea, banana and ...eucalyptus plantations as well as maize fields and small farms. We previously showed presence of pesticides with potential endocrine disruptive effects in the vicinity. To further investigate the water pollution linked to agricultural pressure in this protected area, we implemented a complementary monitoring strategy based on: analytical chemistry, effects based methods and the deployment of Polar Organic Chemical Integrative Samplers (POCIS). Chemical analysis of the POCIS extracts revealed the presence of 13 pesticides: carbofuran, DEET, 2.4-D amine, carbaryl, ametryn, isoproturon, metolachlor, terbutryn, dimethoate, imidacloprid, picaridin, thiamethoxam, carbendazim, with the first three being present in the largest quantities. Water samples collected at the POCIS sampling sites exhibited thyroid and estrogen axis disrupting activities in vivo, in addition to developmental and behaviour effects on Xenopus laevis tadpoles model. Based on our observations, for the health of local human and wildlife populations, further monitoring as well as actions to reduce agrochemical use should be considered in the Kibale National Park and in regions exposed to similar conditions.
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•The Kibale national park (KNP) in Uganda is a hotspot of biodiversity.•Wildlife in the northern part of KNP is threatened by the presence of phytochemicals.•Chemical analysis of local river water revealed the presence of 13 pesticides.•Local river water exhibited thyroid and estrogen disrupting activities in vivo.•Further monitoring and pesticide usage reduction should be considered in KNP.
Water collected in Kibale national park in Uganda contains 13 pesticides and exhibits thyroid and estrogen axis disruption in aquatic larvae.
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