Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio , as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay.

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 in vivo and in vitro. 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.

Introduction: An early diagnosis is crucial in reducing mortality among people who have breast cancer (BC). There is a shortfall of characteristic early clinical symptoms in BC patients, highlighting the importance of investigating new methods for its early detection. A promising novel approach is the analysis of volatile organic compounds (VOCs) produced and emitted through the metabolism of cancer cells. Methods: The purpose of this systematic review is to outline the published research regarding BC-associated VOCs. For this, headspace analysis of VOCs was explored in patient-derived body fluids, animal model-derived fluids, and BC cell lines to identify BC-specific VOCs. A systematic search in PubMed and Web of Science databases was conducted according to the PRISMA guidelines. Results: Thirty-two studies met the criteria for inclusion in this review. Results highlight that VOC analysis can be promising as a potential novel screening tool. However, results of in vivo, in vitro and case-control studies have delivered inconsistent results leading to a lack of inter-matrix consensus between different VOC sampling methods. Discussion: Discrepant VOC results among BC studies have been obtained, highly due to methodological discrepancies. Therefore, methodological issues leading to disparities have been reviewed and recommendations have been made on the standardisation of VOC collection and analysis methods for BC screening, thereby improving future VOC clinical validation studies.

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.

Background: Remote medical scent detection of cancer and infectious diseases with dogs and rats has been an increasing field of research these last 20 years. If validated, the possibility of implementing such a technique in the clinic raises many hopes. This systematic review was performed to determine the evidence and performance of such methods and assess their potential relevance in the clinic. Methods: Pubmed and Web of Science databases were independently searched based on PRISMA standards between 01/01/2000 and 01/05/2021. We included studies aiming at detecting cancers and infectious diseases affecting humans with dogs or rats. We excluded studies using other animals, studies aiming to detect agricultural diseases, diseases affecting animals, and others such as diabetes and neurodegenerative diseases. Only original articles were included. Data about patients’ selection, samples, animal characteristics, animal training, testing configurations, and performances were recorded. Results: A total of 62 studies were included. Sensitivity and specificity varied a lot among studies: While some publications report low sensitivities of 0.17 and specificities around 0.29, others achieve rates of 1 sensitivity and specificity. Only 6 studies were evaluated in a double-blind screening-like situation. In general, the risk of performance bias was high in most evaluated studies, and the quality of the evidence found was low. Conclusions: Medical detection using animals’ sense of smell lacks evidence and performances so far to be applied in the clinic. What odors the animals detect is not well understood. Further research should be conducted, focusing on patient selection, samples (choice of materials, standardization), and testing conditions. Interpolations of such results to free running detection (direct contact with humans) should be taken with extreme caution. Considering this synthesis, we discuss the challenges and highlight the excellent odor detection threshold exhibited by animals which represents a potential opportunity to develop an accessible and non-invasive method for disease detection.