Modifications épigénétiques associées aux effets physiopathologiques de l'exposition au plomb

Aperçu: G.M.

L'exposition au plomb (Pb) à différents stades de développement a montré des résultats physiopathologiques en fonction de la dose, de la durée, du sexe et des tissus, en raison d'une modification de la régulation épigénétique via (a) la méthylation de l'ADN, (b) les modifications d'histone, (c) les miARN et (d ) accessibilité de la chromatine. 

L'altération de la régulation épigénétique induite par le plomb entraîne des conséquences physiopathologiques neurotoxiques et extra-neurotoxiques. Les effets neurotoxiques du Pb comprennent le dysfonctionnement de la mémoire et de l'apprentissage, les troubles du comportement, le trouble du déficit de l'attention avec hyperactivité, les "troubles du spectre de l'autisme" , le vieillissement, la maladie d'Alzheimer, la tauopathie et la neurodégénérescence. Les effets extra-neurotoxiques du Pb comprennent une modification du poids corporel, des troubles métaboliques, des troubles cardiovasculaires, des troubles hématopoïétiques et des troubles de la reproduction. L'exposition au Pb, soit tôt dans la vie, soit à n'importe quel stade de développement, entraîne des effets pathophysiologiques indésirables qui tendent à se apparaître et à se maintenir toute la vie.

J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2019 Aug 12:1-53. doi: 10.1080/10590501.2019.1640581. [Epub ahead of print]

Epigenetic modifications associated with pathophysiological effects of lead exposure

Khalid M¹, Abdollahi M^1,2.

Author information

1

a Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences (TUMS) , Tehran , Iran.

2

b Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran.

Abstract

Lead (Pb) exposure during different stages of development has demonstrated dose, duration, sex, and tissue-specific pathophysiological outcomes due to altered epigenetic regulation via (a) DNA methylation, (b) histone modifications, (c) miRNAs, and (d) chromatin accessibility. Pb-induced alteration of epigenetic regulation causes neurotoxic and extra-neurotoxic pathophysiological outcomes. Neurotoxic effects of Pb include dysfunction of memory and learning, behavioral disorder, attention deficit hyperactivity disorder, autism spectrum disorder, aging, Alzheimer's disease, tauopathy, and neurodegeneration. Extra-neurotoxic effects of Pb include altered body weight, metabolic disorder, cardiovascular disorders, hematopoietic disorder, and reproductive impairment. Pb exposure either early in life or at any stage of development results in undesirable pathophysiological outcomes that tends to sustain and maintain for a lifetime.

PMID:31402779

DOI:10.1080/10590501.2019.1640581

Toxicologie foetale

Aperçu: G.M.a

Les produits chimiques toxiques, d'origine naturelle ou artificielle, sont omniprésents dans notre environnement. Beaucoup de produits chimiques synthétiques rendent la vie plus confortable et la production continue donc de croître. Simultanément à l’augmentation de la production, une augmentation des troubles du développement neurologique a été observée. Certains produits chimiques ne sont pas biodégradables ou ont une très longue période de demi-vie et, malgré le fait que leur production a été fortement réduite, ils sont encore omniprésents dans l'environnement. 

L'exposition fœtale à des produits chimiques toxiques dépend de l'exposition de la mère à ces produits chimiques et du stade de développement du fœtus. La neurodégénérescence humaine a été étudiée dans divers neurotoxiques (alcool, particules fines, métaux et substances chimiques perturbant le système endocrinien). 

Les données suggèrent que la présence d'alcool, de MeOH, de pesticides organochlorés et d'OPP, de biphényles polychlorés, de biphényles polychlorés, de biphényles polychlorés, de biphényles polychlorés, de biphényles polychlorés et d'éthers de biphényles polychlorés (PBDE) , PBDE et bisphénol A augmentent le risque de développer soit un déficit de l'attention / hyperactivité et / ou des "troubles du spectre de l'autisme". 

Le développement psychomoteur semble être moins affecté. Cependant, les données ne sont pas concluantes, ce qui peut dépendre de l'évaluation de l'exposition et du niveau d'exposition, entre autres facteurs.

Handb Clin Neurol. 2019;162:31-55. doi: 10.1016/B978-0-444-64029-1.00002-3.

Fetal toxicology

van de Bor M¹.

Author information

1

Department of Environment and Health, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. Electronic address: margot.vande.bor@vu.nl.

Abstract

Toxic chemicals, either from natural sources or man-made, are ubiquitous in our environment. Many of the synthetic chemicals make life more comfortable and therefore production continues to grow. Simultaneously with the increase in production, an increase in neurodevelopmental disorders has been observed. Some chemicals are not biodegradable or have a very long half-life time and, despite the fact that production of a number of those chemicals has been severely reduced, they are still ubiquitous in the environment. Fetal exposure to toxic chemicals is dependent on maternal exposure to those chemicals and the developing stage of the fetus. Human evidence from epidemiologic studies is described with regard to the effect of prenatal exposure to various groups of neurotoxicants (alcohol, particulate fine matter, metals, and endocrine disrupting chemicals) on neurobehavior development. Data indicate that prenatal exposure to alcohol, polycyclic aromatic hydrocarbons, lead, methylmercury (MeHg), organophosphate pesticides (OPPs), and polychlorinated biphenyl ethers (PBDEs) impair cognitive development, whereas exposure to alcohol, MeHg, organochlorine pesticides and OPPs, polychlorinated biphenyls, PBDEs, and bisphenol A increases the risk of developing either attention deficit/hyperactivity and/or autism spectrum disorders. Psychomotor development appears to be less affected. However, data are not conclusive, which may depend on the assessment of exposure and the exposure level, among other factors.

Copyright © 2019 Elsevier B.V. All rights reserved.

PMID:31324317

DOI: 10.1016/B978-0-444-64029-1.00002-3

La dérégulation foetal et postnatale des métaux dans l'autisme

Aperçu: G.M.

Des facteurs génétiques et environnementaux contribuent aux étiologies du "trouble du spectre de l'autisme" (TSA) mais les preuves d'expositions environnementales spécifiques et de fenêtres de sensibilité sont limitées. Ici, l'équipe étudie des jumeaux monozygotes et dizygotiques discordants pour le TSA afin de vérifier si la dysrégulation des métaux du foetus et postnatale augmente le risque de TSA. 

Des divergences significatives sont apparentes dans l'absorption de métal entre les cas de TSA et leurs frères et sœurs témoins, mais seulement pendant des périodes de développement isolées.

Les cas ont réduit l'absorption d'éléments essentiels de manganèse et de zinc et ont augmenté l'absorption de neurotoxine. Le manganèse et le plomb sont également corrélés avec la sévérité du TSA et des traits autistiques. Cette étude suggère que l'absorption toxique des métaux et la carence en éléments essentiels lors de fenêtres de développement spécifiques augmentent le risque et la gravité des TSA, en soutenant l'hypothèse d'une dysrégulation élémentaire systémique dans les TSA.  

 

Nat Commun. 2017 Jun 1;8:15493. doi: 10.1038/ncomms15493.

Fetal and postnatal metal dysregulation in autism

Arora M¹, Reichenberg A^1,2, Willfors C^3,4, Austin C¹, Gennings C¹, Berggren S^3,4, Lichtenstein P⁵, Anckarsäter H⁶, Tammimies K^3,4, Bölte S^3,4.

Author information

1

Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1057, New York, New York 10029, USA.

2

Seaver Autism Center for Research and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1230, New York, New York 10029, USA.

3

Department of Women's and Children's Health, Center of Neurodevelopmental Disorders (KIND), Karolinska Institutet, Floor 8, Gävlegatan 22, SE-11330 Stockholm, Sweden.

4

Center for Psychiatry Research, Stockholm County Council, Norra Stationsgatan 69, Floor 7, SE-11364 Stockholm, Sweden.

5

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.

6

Institute of Neuroscience and Physiology, University of Gothenburg, Box 430, SE-405 30 Göteborg, Sweden.

Abstract

Genetic and environmental factors contribute to the etiologies of autism spectrum disorder (ASD), but evidence of specific environmental exposures and susceptibility windows is limited. Here we study monozygotic and dizygotic twins discordant for ASD to test whether fetal and postnatal metal dysregulation increases ASD risk. Using validated tooth-matrix biomarkers, we estimate pre- and post-natal exposure profiles of essential and toxic elements. Significant divergences are apparent in metal uptake between ASD cases and their control siblings, but only during discrete developmental periods. Cases have reduced uptake of essential elements manganese and zinc, and higher uptake of the neurotoxin lead. Manganese and lead are also correlated with ASD severity and autistic traits. Our study suggests that metal toxicant uptake and essential element deficiency during specific developmental windows increases ASD risk and severity, supporting the hypothesis of systemic elemental dysregulation in ASD. Independent replication in population-based studies is needed to extend these findings.

PMID:28569757

DOI:10.1038/ncomms15493

Proximité résidentielle prénatale de l'utilisation de pesticides agricoles et QI chez les enfants de 7 ans

Aperçu: G.M.

La proximité résidentielle de l'utilisation de pesticides agricoles a été associée à des anomalies du tube neural et à l'autisme, mais des résultats plus subtils comme la cognition n'ont pas été étudiés.

L'étude a évalué la relation entre la proximité résidentielle prénatale à l'utilisation agricole de pesticides potentiellement neurotoxiques et le développement neurologique chez les enfants de 7 ans. 

Les chercheurs ont mis en évidence une diminution de 2,2 points [intervalle de confiance de 95% (IC): dans le QI à pleine échelle et 2,9 points (IC 95%) dans la compréhension verbale pour chaque augmentation de l'écart type de l'utilisation pondérée par la toxicité des pesticides organophosphorés.

Ils ont donc identifié des relations potentielles entre la proximité résidentielle maternelle de  l'utilisation agricole de pesticides neurotoxiques et le développement neurologique atténué chez les enfants .

Cliquer ICI pour accéder à l'intégralité de l'article en anglais

Environ Health Perspect. 2017 May 25;125(5):057002. doi: 10.1289/EHP504.

Prenatal Residential Proximity to Agricultural Pesticide Use and IQ in 7-Year-Old Children

Gunier RB¹, Bradman A¹, Harley KG¹, Kogut K¹, Eskenazi B¹.

Author information

1

School of Public Health, University of California, Berkeley , Berkeley, California, USA.

Abstract

BACKGROUND:

Residential proximity to agricultural pesticide use has been associated with neural tube defects and autism, but more subtle outcomes such as cognition have not been studied.

OBJECTIVES:

We evaluated the relationship between prenatal residential proximity to agricultural use of potentially neurotoxic pesticides and neurodevelopment in 7-year-old children.

METHODS:

Participants included mothers and children ([Formula: see text]) living in the agricultural Salinas Valley of California enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study. We estimated agricultural pesticide use within 1 km of maternal residences during pregnancy using a geographic information system, residential location, and California's comprehensive agricultural Pesticide Use Report data. We used regression models to evaluate prenatal residential proximity to agricultural use of five potentially neurotoxic pesticide groups (organophosphates, carbamates, pyrethroids, neonicotinoids, and manganese fungicides) and five individual organophosphates (acephate, chlorpyrifos, diazinon, malathion, and oxydemeton-methyl) and cognition in 7-year-old children. All models included prenatal urinary dialkyl phosphate metabolite concentrations.

RESULTS:

We observed a decrease of 2.2 points [95% confidence interval (CI): [Formula: see text], [Formula: see text]] in Full-Scale IQ and 2.9 points (95% CI: [Formula: see text], [Formula: see text]) in Verbal Comprehension for each standard deviation increase in toxicity-weighted use of organophosphate pesticides. In separate models, we observed similar decrements in Full-Scale IQ with each standard deviation increase of use for two organophosphates (acephate and oxydemeton-methyl) and three neurotoxic pesticide groups (pyrethroids, neonicotinoids, and manganese fungicides).

CONCLUSIONS:

This study identified potential relationships between maternal residential proximity to agricultural use of neurotoxic pesticides and poorer neurodevelopment in children. https://doi.org/10.1289/EHP504.

BACKGROUND:

Residential proximity to agricultural pesticide use has been associated with neural tube defects and autism, but more subtle outcomes such as cognition have not been studied.

OBJECTIVES:

We evaluated the relationship between prenatal residential proximity to agricultural use of potentially neurotoxic pesticides and neurodevelopment in 7-year-old children.

METHODS:

Participants included mothers and children ([Formula: see text]) living in the agricultural Salinas Valley of California enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study. We estimated agricultural pesticide use within 1 km of maternal residences during pregnancy using a geographic information system, residential location, and California’s comprehensive agricultural Pesticide Use Report data. We used regression models to evaluate prenatal residential proximity to agricultural use of five potentially neurotoxic pesticide groups (organophosphates, carbamates, pyrethroids, neonicotinoids, and manganese fungicides) and five individual organophosphates (acephate, chlorpyrifos, diazinon, malathion, and oxydemeton-methyl) and cognition in 7-year-old children. All models included prenatal urinary dialkyl phosphate metabolite concentrations.

RESULTS:

We observed a decrease of 2.2 points [95% confidence interval (CI): [Formula: see text], [Formula: see text]] in Full-Scale IQ and 2.9 points (95% CI: [Formula: see text], [Formula: see text]) in Verbal Comprehension for each standard deviation increase in toxicity-weighted use of organophosphate pesticides. In separate models, we observed similar decrements in Full-Scale IQ with each standard deviation increase of use for two organophosphates (acephate and oxydemeton-methyl) and three neurotoxic pesticide groups (pyrethroids, neonicotinoids, and manganese fungicides).

CONCLUSIONS:

This study identified potential relationships between maternal residential proximity to agricultural use of neurotoxic pesticides and poorer neurodevelopment in children. https://doi.org/10.1289/EHP504.

PMID: 28557711

DOI: 10.1289/EHP504

Mercure, arsenic, cadmium et plomb dans le sang chez les enfants avec un diagnostic de trouble du spectre de l'autisme

Aperçu: G.M.

Les facteurs environnementaux ont été impliqués dans l'étiologie du trouble du spectre de l'autisme  (TSA); Cependant, le rôle des métaux lourds n'a pas été entièrement défini. Cette étude a permis de déterminer si les concentrations sanguines de mercure, d'arsenic, de cadmium et de plomb chez les enfants avec un diagnostic de TSA diffèrent sensiblement de celles des témoins appariés selon l'âge et le sexe.

Cent quatre-vingts enfants non apparentés avec un diagnostic de TSA et 184 contrôles sans TSA ont été recrutés. Les données ont montré que les enfants avec un diagnostic de TSA avaient des niveaux significativement plus élevés de mercure et d'arsenic et un taux de cadmium inférieur.  

Les niveaux de plomb n'ont pas varié de manière significative entre les groupes. 

Les résultats de cette étude sont cohérents avec de nombreuses études antérieures, qui montrent un rôle important pour l'exposition aux métaux lourds, en particulier le mercure, dans l'étiologie des TSA.  

Biol Trace Elem Res. 2017 May 8. doi: 10.1007/s12011-017-1002-6.

Blood Mercury, Arsenic, Cadmium, and Lead in Children with Autism Spectrum Disorder

Li H¹, Li H², Li Y¹, Liu Y¹, Zhao Z^3,4.

Author information

1

Children's Hospital of Zhejiang University School of Medicine, Hangzhou, People's Republic of China.

2

Laboratory of Neuroinflammation, StVincent's Centre for Applied Medical Research and University of New South Wales, Sydney, NSW, Australia.

3

Children's Hospital of Zhejiang University School of Medicine, Hangzhou, People's Republic of China. zhaozy@zju.edu.cn.

4

Department of Pediatric Health Care, Children's Hospital of Zhejiang University School of Medicine, 57 Zhuganxiang Road, Hangzhou, People's Republic of China, 310003. zhaozy@zju.edu.cn.

Abstract

Environmental factors have been implicated in the etiology of autism spectrum disorder (ASD); however, the role of heavy metals has not been fully defined. This study investigated whether blood levels of mercury, arsenic, cadmium, and lead of children with ASD significantly differ from those of age- and sex-matched controls. One hundred eighty unrelated children with ASD and 184 healthy controls were recruited. Data showed that the children with ASD had significantly (p < 0.001) higher levels of mercury and arsenic and a lower level of cadmium. The levels of lead did not differ significantly between the groups. The results of this study are consistent with numerous previous studies, supporting an important role for heavy metal exposure, particularly mercury, in the etiology of ASD. It is desirable to continue future research into the relationship between ASD and heavy metal exposure.

PMID: 28480499

DOI: 10.1007/s12011-017-1002-6

Relation entre le sélénium, le plomb et le mercure dans les globules rouges des enfants autistes saoudiens

Aperçu: G.M.

Les données obtenues démontrent une élévation significative du Hg et du Pb ainsi qu'une diminution significative des taux de Se dans les globules rouges des patients avec TSA par rapport aux témoins sans TSA.

Metab Brain Dis. 2017 Mar 21. doi: 10.1007/s11011-017-9996-1.

Relationship between selenium, lead, and mercury in red blood cells of Saudi autistic children

El-Ansary A^1,2,3, Bjørklund G⁴, Tinkov AA^5,6,7, Skalny AV^6,7,8,9, Al Dera H^10,11.

Author information

1

Central Laboratory, Center for Female Scientific and Medical Colleges, King Saud University, Riyadh, Saudi Arabia.

2

Autism Research and Treatment Center, Riyadh, Saudi Arabia.

3

Medicinal Chemistry Department, National Research Centre, Dokki, Cairo, Egypt.

4

Council for Nutritional and Environmental Medicine, Toften 24, 8610, Mo i Rana, Norway. bjorklund@conem.org.

5

Orenburg State University, Orenburg, Russia.

6

Orenburg State Medical University, Orenburg, Russia.

7

Yaroslavl State University, Yaroslavl, Russia.

8

RUDN University, Moscow, Russia.

9

All-Russian Research Institute of Medicinal and Aromatic Plants, Moscow, Russia.

10

Basic Medical Science Department, College of Medicine, King Saud bin Abdul Aziz University for Health Sciences, Riyadh, Saudi Arabia.

11

King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause significant social, communication and behavioral challenges. Environmental contribution to ASD is due in large part to the sensitivity of the developing brain to external exposures such as lead (Pb), and mercury (Hg) as toxic heavy metals or due to a poor detoxification ability as the phenotype of this disorder. Selenium (Se) as an antioxidant element that counteracts the neurotoxicity of Hg, and Pb, presumably through the formation of nontoxic complexes. In the present study, Pb, Hg, and Se were measured in red blood cells (RBCs) of 35 children with ASD and 30 age- and gender-matched healthy control children using atomic absorption spectrometry. Receiver Operating Characteristics (ROC) analysis of the obtained data was performed to measure the predictive value of their absolute and relative concentrations. The obtained data demonstrates a significant elevation of Hg and Pb together with a significant decrease in the Se levels in RBCs of patients with ASD when compared to the healthy controls. The ratios of Se to both Pb and Hg were remarkably altered, being indicative of heavy metal neurotoxicity in patients with ASD. In conclusion, the present study indicates the importance of Se for prevention and/or therapy of heavy metal neurotoxicity.

PMID: 28326463

DOI: 10.1007/s11011-017-9996-1