Xavier Coumoul

Université de Paris · INSERM UMR-S 1124

The aryl hydrocarbon receptor (AHR) is a sensor of low-molecular-weight molecule signals that originate from environmental exposures, the microbiome, and host metabolism. Building upon initial studies examining anthropogenic chemical exposures, the list of AHR ligands of microbial, diet, and host metabolism origin continues to grow and has provided...

Human placenta is a multifunctional interface between maternal and fetal blood. Studying the impact of pollutants on this organ is crucial because many xenobiotics in maternal blood can accumulate in placental cells or pass into the fetal circulation. Benzo(a)pyrene (BaP) and cerium dioxide nanoparticles (CeO2 NP), which share the same emission sou...

Background: Acrylamide is classified as a probable human carcinogen by the IARC but epidemiological evidence on the carcinogenicity of acrylamide from dietary sources is limited. This study aimed to investigate the associations between dietary acrylamide and breast cancer risk in the NutriNet-Santé cohort. Methods: This prospective cohort study inc...

Since the initial development of the exposome concept, much of the effort has been devoted to the characterization of the exposome through analytical, epidemiological, and toxicological/mechanistical studies. There is now an urgent need to link the exposome to human diseases and to include exposomics in the characterization of environment-linked pa...

Background: Prenatal exposure to persistent organic pollutants (POPs) may contribute to the development of childhood obesity and metabolic disorders. However, little is known about whether the maternal nutritional status during pregnancy can modulate these associations. Objectives: The main objective was to characterize the joint associations an...

Breast cancer is a major public health issue and the role of pollutants in promoting breast cancer progression has recently been suggested. We aimed to assess if a mixture of pollutants, cigarette smoke, could favor the aggressivity of breast cancer cells. We also evaluated the impact of the tumor micro-environment, largely represented by adipocyte...

Parkinson's disease is a severe neurodegenerative disease. Several environmental contaminants such as pesticides have been suspected to favor the appearance of this pathology. The protein DJ-1 (or Park7) protects against the development of Parkinson's disease. Thus, the possible inhibitory effects of about a hundred pesticides on human DJ-1 have be...

Blood is the most widely used matrix for biomonitoring of persistent organic pollutants (POPs). It is assumed that POPs are homogenously distributed within body lipids at steady state; however, the variability underlying the partitioning of POPs between fat compartments is poorly understood. Hence, the objective of this study was to review the stat...

For more than a decade, there has been a wide debate about the branched-chain amino acids (BCAA) leucine, valine, and isoleucine, with, on the one hand, the supporters of their anabolic effects and, on the other hand, those who suspect them of promoting insulin resistance. Indeed, the role of leucine in the postprandial activation of protein synthe...

Persistent organic pollutants (POPs) accumulate in the organisms due to their hydrophobicity and resistance to xenobiotic metabolism. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of most representative POPs. Its pathophysiological effects have been extensively studied on many types of tissues but not on muscles. In this study, female C57BL/6J...

The emergence and circulation of a novel coronavirus (2019-nCoV)-Severe acute respiratory syndrome coronavi-rus 2 (SARS-CoV-2)-set off a global health crisis. SARS-CoV-2 spreads faster than its two ancestors, SARS-CoV and MERS-CoV. Several modes of transmission have been identified: via respiratory droplets, contact with infected people or contamin...

Introduction Breast cancer (BC) is frequent with a poor prognosis in case of metastasis. The role of the environment has been poorly evaluated in its progression. We searched to assess whether a mixture of pollutants could be responsible of BC aggressiveness. Methods Patients undergoing surgery for their BC were prospectively included in the METAP...

Background Food additive emulsifiers are found in thousands of industrial foods and may exert deleterious effects on gut microbiota and carcinogenesis according to experimental studies. However, their associations with cancer risk has not been investigated yet. This study aimed to investigate these associations in a large population-based prospecti...

Background Acrylamide is classified as a probable human carcinogen by the IARC but epidemiological evidence on the carcinogenicity of acrylamide from dietary sources is limited. This study aimed to investigate the associations between dietary acrylamide and breast cancer risk in the NutriNet-Santé cohort. Methods This prospective cohort study incl...

Background Acrylamide is classified as a probable human carcinogen by the International Agency for Research on Cancer but epidemiologic evidence on the carcinogenicity of acrylamide from dietary sources is limited. Objectives This study aimed to investigate the associations between dietary acrylamide and breast cancer risk in the NutriNet-Santé co...

The role of the environment in breast cancer (BC) progression has recently been suggested. We aimed to assess if a mixture of pollutants, cigarette smoke, could favor its aggressivity. We also evaluated the impact of the micro-environment, largely represented by adipocytes, in mediating this. BC cells lines MCF-7 were cultured using a transwell co-...

https://www.sciencedirect.com/science/article/pii/S0006295222002386

The prevalence of metabolic diseases, such as obesity, diabetes, metabolic syndrome, and chronic liver diseases among others, has been rising for several years. Epidemiology and mechanistic (in vivo, in vitro and in silico) toxicology have recently provided compelling evidence implicating the chemical environment in the pathogenesis of these diseas...

Investigation of the toxicity triggered by chemicals on the human brain has traditionally relied on approaches using rodent in vivo models and in vitro cell models including primary neuronal cultures and cell lines from rodents. The issues of species differences between humans and rodents, the animal ethical concerns and the time and cost required...

The aryl hydrocarbon receptor (AHR) regulates the expression of numerous genes in response to activation by agonists including xenobiotics. Although it is well appreciated that environmental signals and cell intrinsic features may modulate this transcriptional response, how it is mechanistically achieved remains poorly understood. We show that hexo...

Adverse outcome pathways (AOPs) are formalized and structured linear concepts that connect one molecular initiating event (MIE) to an adverse outcome (AO) via different key events (KE) through key event relationships (KER). They are mainly used in eco-toxicology toxicology, and regulatory health issues. AOPs must respond to specific guidelines from...

Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obe...

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor whose activity can be modulated by polyphenols, such as curcumin. AhR and curcumin have evolutionarily conserved effects on aging. Here, we investigated whether and how the AhR mediates the anti-aging effects of curcumin across species. Using a combination of in vivo, in...

Caenorhabditis elegans is an important model used for many aspects of biological research. Its genome contains 76 genes coding for cytochromes P450 (P450s), and few data about the biochemical properties of those P450s have been published so far. However, an increasing number of articles have appeared on their involvement in the metabolism of xenobi...

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor whose activity can be modulated by polyphenols such as curcumin. AhR and curcumin have evolutionarily conserved effects on aging. Here, we investigated whether and how the AhR mediates the anti-aging effects of curcumin across species. Using a combination of in vivo, in...

The exposome concept encourages holistic consideration of the non-genetic factors (environmental exposures including lifestyle) that influence an individual’s health over their life course. However, disconnect between the concept and practical application has promoted divergent interpretations of the exposome across disciplines and reinforced separ...

Aryl hydrocarbon receptor (AhR) ligands are recognized as aggravating factors in cardiovascular diseases but little is known about the role of the AhR in atherosclerosis considering the effects of age and gender. We exposed male and female ApoE knock-out mice, a model to study the pathogenesis of atherosclerosis, to a potent AhR ligand, 2,3,7,8-tet...

The aryl hydrocarbon receptor (AhR) is a transcriptional factor that regulates multiple functions following its activation by a variety of ligands, including xenobiotics, natural products, microbiome metabolites, and endogenous molecules. Because of this diversity, the AhR constitutes an exposome receptor. One of its main functions is to regulate s...

Environmental factors including diet, sedentary lifestyle and exposure to pollutants largely influence human health throughout life. Cellular and molecular events triggered by an exposure to environmental pollutants are extremely variable and depend on the age, the chronicity and the doses of exposure. Only a fraction of all relevant mechanisms inv...

The development of the exposome concept has been one of the hallmarks of environmental and health research for the last decade. The exposome encompasses the life course environmental exposures including lifestyle factors, from the prenatal period onwards. It has inspired many research programs and is expected to influence environmental and health r...

We hypothesized that an interplay between aryl hydrocarbon receptor (AhR) and cysteine-related thiolome at the kidney cortex underlies the mechanisms of (mal)adaptation to chronic intermittent hypoxia (CIH), promoting arterial hypertension (HTN). Using a rat model of CIH-HTN, we investigated the impact of short-term (1 and 7 days), mid-term (14 and...

Endocrine disruptors: WHAT ARE WE TALKING ABOUT AND WHAT NEW MECHANISMS OF TOXICITY DO THEY BRING INTO PLAY? Endocrine disruptors (EDs) are chemicals that can interfere with the functioning of the endocrine system and thereby cause an adverse event. They are suspected of being toxic to the environment and to humans and to increase the risk of deve...

WHAT IS KNOWN ABOUT THE ACTION OF ENDOCRINE DISRUPTORS ON THE IMMUNE SYSTEM? The immune system (innate and adaptive immunity), involves different tissues and cell types to defend the body against external aggressions. This physiological mechanism involves some hormonal systems for its proper functioning. Moreover, new relationships between the immu...

Pesticides: WHAT IS KNOWN OR SUSPECTED ABOUT THEIR HARMFUL EFFECTS ON HEALTH Pesticides are molecules of various kinds used to combat harmful organisms (insects, weeds, fungi…). Their non-specificity means that they also have an impact on human health at many levels (cancers, Parkinson's disease, developmental problems in children), as shown by th...

Les populations humaines, quel que soit le contexte socioéconomique, sont exposées à de nombreuses molécules polluantes et/ou contaminantes tout au long de leur vie. Cette exposition à des mélanges potentiellement variables tout au long de la vie d’un individu a été résumée sous le concept d’exposome (qui inclut à la fois les environnements chimiqu...

Growing epidemiological evidence suggests that organochlorine chemicals (OCCs), including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may play a role in the pathogenesis of endometriosis. Objectives: We aimed to systematically review the experimental evidence (in vivo and in vitro) on the associations between exposure to OCCs and endometriosis-rel...

Background: Exposure to endocrine disrupting chemicals (EDCs) represents a critical public health threat. Several adverse health outcomes (e.g., cancers, metabolic and neurocognitive/neurodevelopmental disorders, infertility, immune diseases and allergies) are associated with exposure to EDCs. However, the regulatory tests that are currently emplo...

Background: Breast cancer (BC) is a major public health concern, and its prognosis is very poor once metastasis occurs. The tumor microenvironment and chemical pollution have been suggested recently to contribute, independently, to the development of metastatic cells. The BC microenvironment consists, in part, of adipocytes and preadipocytes in wh...

Low levels of the neurotransmitter serotonin have been associated with the onset of depression. While traditional treatments include antidepressants, physical exercise has emerged as an alternative for patients with depressive disorders. Yet there remains the fundamental question of how exercise is sensed by the brain. The existence of a muscle–bra...

Preeclampsia, a hypertensive disorder occurring during pregnancy, is characterized by excessive oxidative stress and trophoblast dysfunction with dysregulation of soluble Fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) production. Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase (Nox) is the major source of placent...

Aims To explore exposure to 22 persistent organic pollutants (POPs) and incident type 2 diabetes in a population-based, prospective cohort. Methods This case-cohort study on 753 participants without type 2 diabetes at baseline, was followed-up over nine years, as part of the French D.E.S.I.R. cohort. We measured 22 POPs in fasting serum at baselin...

Teaching has taken many forms in history, from the dialectical style between the teacher and her/his fellows (in Ancient Greece) to lectures in amphitheaters in front of large audiences. The latter form has been traditionally used in universities, but it is hard to imagine using methods on young audiences (e.g., kindergarten). Instead, other techni...

Research has shown how the blended learning approach leads to enhanced learning for students due to the combination of web-based technology such as video production with face-to-face teacher-led training. One aspect explored in this study is the use of a lightboard in video production to solve the challenges of a traditional whiteboard setup for ed...

Breast cancer (BC) is one of the most common causes of cancer in the world and the second leading cause of cancer deaths among women. Mortality is associated mainly with the development of metastases. Identification of the mechanisms involved in metastasis formation is, therefore, a major public health issue. Among the proposed risk factors, chemic...

Human malignant glioblastoma (GBM) is a highly invasive and lethal brain tumor. Targeting of integrin downstream signaling mediators in GBM such as focal adhesion kinase (FAK) seems reasonable and recently demonstrated promising results in early clinical studies. Herein, we report the structure-guided development of a series of covalent inhibitors...

Background Patients at high risk of severe forms of COVID-19 frequently suffer from chronic diseases, but other risk factors may also play a role. Environmental stressors, such as endocrine disrupting chemicals (EDCs), can contribute to certain chronic diseases and might aggravate the course of COVID-19. Objectives To explore putative links betwee...

Background: Patients at high risk of severe forms of COVID-19 frequently suffer from chronic diseases, but other risk factors may also play a role. Environmental stressors, such as endocrine disrupting chemicals (EDCs), can contribute to certain chronic diseases and might aggravate the course of COVID-19. Objectives: To explore putative links betwe...

The human placenta is at the interface between maternal and fetal circulations, and is crucial for fetal development. The nanoparticles of cerium dioxide (CeO2 NPs) from air pollution are an unevaluated risk during pregnancy. Assessing the consequences of placenta exposure to CeO2 NPs could contribute to a better understanding of NPs’ effect on the...

Motivation: Exposure to pesticides may lead to adverse health effects in human populations, in particular vulnerable groups. The main long-term health concerns are neurodevelopmental disorders, carcinogenicity as well as endocrine disruption possibly leading to reproductive and metabolic disorders. Adverse Outcome Pathways (AOP) consist in linear...

Background and purpose: Obstructive sleep apnea (OSA) is associated to a high prevalence of resistant arterial hypertension (HTN) justifying the research on novel targets. Chronic intermittent hypoxia (CIH) is a key feature in the development of OSA comorbidities, including HTN. Experimental approach: We used a rat model of CIH-induced HTN to di...

Exposure to chemical substances that can produce endocrine disrupting effects represents one of the most critical public health threats nowadays. In line with the regulatory framework implemented within the European Union (EU) to reduce the levels of endocrine disruptors (EDs) for consumers, new and effective methods for ED testing are needed. The...

The oral cavity is one of the main route for environmental contaminations associated to many chronic diseases (cancers, fertility and behavior disorders for example) via alimentation, medications and respiration. These environmental factors including, among others, endocrine disruptors and excessive fluoride can disrupt dental development and thus...

La cavité buccale est l’une des voies majeures des contaminations environnementales connues pour être impliquées dans de nombreuses maladies chroniques via l’alimentation, les médications ou même la respiration. D’autres facteurs peuvent également influer sur l’environnement oral, certains endogènes, comme le microbiote, les variations hormonales,...

The oral cavity is one of the main route for environmental contaminations associated to many chronic diseases (cancers, fertility and behavior disorders for example) via alimentation, medications and respiration. These environmental factors including, among others, endocrine disruptors and excessive fluoride can disrupt dental development and thus...

Bisphenol F (BPF) is one of several Bisphenol A (BPA) substituents that is increasingly used in manufacturing industry leading to detectable human exposure. Whereas a large number of studies have been devoted to decipher BPA effects, much less is known about its substituents. In order to support decision making on BPF's safety, we have developed a...

Background: Breast cancer (BC) is a major public health concern with over 2 million new cases diagnosed and over 600,000 deaths in 2018 in women worldwide. When distant metastases are present at diagnosis, the 5-year survival rate is only 26%. Recent studies have suggested that persistent organic pollutants (POPs) that accumulate in adipose tissue...

Individuals as well as entire ecosystems are exposed to mixtures of Persistent Organic Pollutants (POPs). Previously, we showed, by a non-targeted approach, that the expression of several genes involved in carbohydrate metabolism was almost completely inhibited in the human hepatic cell line HepaRG following exposure to a mixture of the organochlor...

Résumé Les maladies métaboliques représentent un problème croissant en termes de santé publique. De nombreux polluants ou contaminants alimentaires sont suspectés de participer à l’émergence de ces pathologies par leur action en tant que perturbateurs endocriniens ou obésogènes. Dans cette revue, nous décrirons les nombreuses voies d’entrée de ces...

In order to help promote instructional change at French‐speaking universities in Europe, we initiated a series of 1‐day events centered on learning innovations. Since 2015, these events have been taking place every 6 months at the Université Paris Descartes, with the moral support of three learned scientific societies, the French Academy of Science...

Background: Available toxicity data can be optimally interpreted if they are integrated using computational approaches such as systems biology modeling. Such approaches are particularly warranted in cases where regulatory decisions have to be made rapidly. Objectives: The study aims at developing and applying a new integrative computational stra...