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Epigenetic Effects and Toxicity of Environmental Pollutants
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Epigenetic Effects and Toxicity of Environmental Pollutants

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 17418

Special Issue Editors

Dr. Antonietta Santoro

E-Mail Website
Guest Editor
Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy
Interests: the effects of environmental pollutants on human health; the role of the endocannabinoid system in the processes of carcinogenicity, inflammation, neurogenesis and neuronal differentiation
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Giovanna Della Porta

E-Mail Website
Guest Editor
Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy
Interests: drug delivery; micro/nano carriers; new technologies for drug carriers development; innovative drug carriers; biopolymers; liposomes; nanogels
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Environmental pollutants including chemical and physical agents, dietary components, and endocrine disruptors, can have long-lasting adverse effects on human health, by affecting reproduction, development and metabolism, even in subsequent generations. Although the underlying mechanisms remain largely unknown, new insights are emerging, which suggest that chronic exposure to environmental pollutants can affect cell metabolism and induce genetic damage and biological adverse effects at both peripheral and central levels, playing a key role in inducing epigenetic changes that could have a trans-generational inheritance in the offspring. From this point of view, it is emerging that environmental pollutants (pesticides, endocrine disruptors and natural/synthetic products also used as cosmetics, nutraceuticals and/or nanomaterials for drug delivery) could be toxic and associated with an increased risk of neurological disorders, reduced fertility and cancer. Therefore, this Special Issue welcomes reviews and research papers which aim to provide an up-to-date report on the adverse effects of environmental pollutants on human health, with particular attention on new pollutants and their emerging epigenetic effects, and molecular interactions in experimental model systems.

Prof. Antonietta Santoro
Prof. Giovanna Della Porta
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • environmental pollutants
  • carcinogens
  • pesticides
  • endocrine disruptors
  • electromagnetic fields
  • nutraceuticals
  • cosmetics
  • nanoparticles
  • epigenetics effects
  • cytotoxicity
  • DNA damage
  • inflammation
  • neurological effects
  • immune system alterations
  • nanotoxicology

Published Papers (5 papers)

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Research

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19 pages, 3763 KiB  
Article
Multi-Systemic Alterations by Chronic Exposure to a Low Dose of Bisphenol A in Drinking Water: Effects on Inflammation and NAD+-Dependent Deacetylase Sirtuin1 in Lactating and Weaned Rats
by Antonietta Santoro, Marika Scafuro, Jacopo Troisi, Giuseppe Piegari, Paola Di Pietro, Elena Mele, Donato Cappetta, Marianna Marino, Antonella De Angelis, Carmine Vecchione, Orlando Paciello, Silvia Fasano, Riccardo Pierantoni, Andrea Viggiano and Rosaria Meccariello
Int. J. Mol. Sci. 2021, 22(18), 9666; https://doi.org/10.3390/ijms22189666 - 07 Sep 2021
Cited by 11 | Viewed by 2835
Abstract
Bisphenol A (BPA) is largely used as a monomer in some types of plastics. It accumulates in tissues and fluids and is able to bypass the placental barrier, affecting various organs and systems. Due to huge developmental processes, children, foetuses, and neonates could [...] Read more.
Bisphenol A (BPA) is largely used as a monomer in some types of plastics. It accumulates in tissues and fluids and is able to bypass the placental barrier, affecting various organs and systems. Due to huge developmental processes, children, foetuses, and neonates could be more sensitive to BPA-induced toxicity. To investigate the multi-systemic effects of chronic exposure to a low BPA dose (100 μg/L), pregnant Wistar rats were exposed to BPA in drinking water during gestation and lactation. At weaning, newborn rats received the same treatments as dams until sex maturation. Free and conjugated BPA levels were measured in plasma and adipose tissue; the size of cerebral ventricles was analysed in the brain; morpho-functional and molecular analyses were carried out in the liver with a focus on the expression of inflammatory cytokines and Sirtuin 1 (Sirt1). Higher BPA levels were found in plasma and adipose tissue from BPA treated pups (17 PND) but not in weaned animals. Lateral cerebral ventricles were significantly enlarged in lactating and weaned BPA-exposed animals. In addition, apart from microvesicular steatosis, liver morphology did not exhibit any statistically significant difference for morphological signs of inflammation, hypertrophy, or macrovesicular steatosis, but the expression of inflammatory cytokines, Sirt1, its natural antisense long non-coding RNA (Sirt1-AS LncRNA) and histone deacetylase 1 (Hdac1) were affected in exposed animals. In conclusion, chronic exposure to a low BPA dose could increase the risk for disease in adult life as a consequence of higher BPA circulating levels and accumulation in adipose tissue during the neonatal period. Full article
(This article belongs to the Special Issue Epigenetic Effects and Toxicity of Environmental Pollutants)
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19 pages, 4403 KiB  
Article
Individual DNA Methylation Pattern Shifts in Nanoparticles-Exposed Workers Analyzed in Four Consecutive Years
by Andrea Rossnerova, Katerina Honkova, Irena Chvojkova, Daniela Pelclova, Vladimir Zdimal, Jaroslav A. Hubacek, Lucie Lischkova, Stepanka Vlckova, Jakub Ondracek, Stepanka Dvorackova, Jan Topinka and Pavel Rossner, Jr.
Int. J. Mol. Sci. 2021, 22(15), 7834; https://doi.org/10.3390/ijms22157834 - 22 Jul 2021
Cited by 7 | Viewed by 1773
Abstract
A DNA methylation pattern represents an original plan of the function settings of individual cells and tissues. The basic strategies of its development and changes during the human lifetime are known, but the details related to its modification over the years on an [...] Read more.
A DNA methylation pattern represents an original plan of the function settings of individual cells and tissues. The basic strategies of its development and changes during the human lifetime are known, but the details related to its modification over the years on an individual basis have not yet been studied. Moreover, current evidence shows that environmental exposure could generate changes in DNA methylation settings and, subsequently, the function of genes. In this study, we analyzed the effect of chronic exposure to nanoparticles (NP) in occupationally exposed workers repeatedly sampled in four consecutive years (2016–2019). A detailed methylation pattern analysis of 14 persons (10 exposed and 4 controls) was performed on an individual basis. A microarray-based approach using chips, allowing the assessment of more than 850 K CpG loci, was used. Individual DNA methylation patterns were compared by principal component analysis (PCA). The results show the shift in DNA methylation patterns in individual years in all the exposed and control subjects. The overall range of differences varied between the years in individual persons. The differences between the first and last year of examination (a three-year time period) seem to be consistently greater in the NP-exposed subjects in comparison with the controls. The selected 14 most differently methylated cg loci were relatively stable in the chronically exposed subjects. In summary, the specific type of long-term exposure can contribute to the fixing of relevant epigenetic changes related to a specific environment as, e.g., NP inhalation. Full article
(This article belongs to the Special Issue Epigenetic Effects and Toxicity of Environmental Pollutants)
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13 pages, 1099 KiB  
Article
Glyphosate and AMPA Induce Alterations in Expression of Genes Involved in Chromatin Architecture in Human Peripheral Blood Mononuclear Cells (In Vitro)
by Ewelina Woźniak, Edyta Reszka, Ewa Jabłońska, Jaromir Michałowicz, Bogumiła Huras and Bożena Bukowska
Int. J. Mol. Sci. 2021, 22(6), 2966; https://doi.org/10.3390/ijms22062966 - 15 Mar 2021
Cited by 11 | Viewed by 2620
Abstract
We have determined the effect of glyphosate and aminomethylphosphonic acid (AMPA) on expression of genes involved in chromatin architecture in human peripheral blood mononuclear cells (PBMCs). The cells were incubated with glyphosate and AMPA in the concentrations ranging from 0.5 to 100 μM [...] Read more.
We have determined the effect of glyphosate and aminomethylphosphonic acid (AMPA) on expression of genes involved in chromatin architecture in human peripheral blood mononuclear cells (PBMCs). The cells were incubated with glyphosate and AMPA in the concentrations ranging from 0.5 to 100 μM and from 0.5, to 250 μM, respectively. The expression profile of the following genes by quantitative Real-Time PCR was evaluated: Genes involved in the DNA methylation (DNMT1, DNMT3A) and DNA demethylation process (TET3) and those involved in chromatin remodeling: genes involved in the modification of histone methylation (EHMT1, EHMT2) and genes involved in the modification of histone deacetylation (HDAC3, HDAC5). Gene profiling showed that glyphosate changed the expression of DNMT1, DMNT3A, and HDAC3, while AMPA changed the expression of DNMT1 and HDAC3. The results also revealed that glyphosate at lower concentrations than AMPA upregulated the expression of the tested genes. Both compounds studied altered expression of genes, which are characteristic for the regulation of transcriptionally inactive chromatin. However, the unknown activity of many other proteins involved in chromatin structure regulation prevents to carry out an unambiguous evaluation of the effect of tested xenobiotics on the studied process. Undoubtedly, we have observed that glyphosate and AMPA affect epigenetic processes that regulate chromatin architecture. Full article
(This article belongs to the Special Issue Epigenetic Effects and Toxicity of Environmental Pollutants)
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19 pages, 1956 KiB  
Article
The Endocrine Disruptor Bisphenol A (BPA) Affects the Enteric Neurons Immunoreactive to Neuregulin 1 (NRG1) in the Enteric Nervous System of the Porcine Large Intestine
by Kamila Szymańska, Krystyna Makowska, Jarosław Całka and Sławomir Gonkowski
Int. J. Mol. Sci. 2020, 21(22), 8743; https://doi.org/10.3390/ijms21228743 - 19 Nov 2020
Cited by 8 | Viewed by 2285
Abstract
The enteric nervous system (ENS), located in the wall of the gastrointestinal (GI) tract, is characterized by complex organization and a high degree of neurochemical diversity of neurons. One of the less known active neuronal substances found in the enteric neurons is neuregulin [...] Read more.
The enteric nervous system (ENS), located in the wall of the gastrointestinal (GI) tract, is characterized by complex organization and a high degree of neurochemical diversity of neurons. One of the less known active neuronal substances found in the enteric neurons is neuregulin 1 (NRG1), a factor known to be involved in the assurance of normal development of the nervous system. During the study, made up using the double immunofluorescence technique, the presence of NRG1 in the ENS of the selected segment of porcine large intestine (caecum, ascending and descending colon) was observed in physiological conditions, as well as under the impact of low and high doses of bisphenol A (BPA) which is commonly used in the production of plastics. In control animals in all types of the enteric plexuses, the percentage of NRG1-positive neurons oscillated around 20% of all neurons. The administration of BPA caused an increase in the number of NRG1-positive neurons in all types of the enteric plexuses and in all segments of the large intestine studied. The most visible changes were noted in the inner submucous plexus of the ascending colon, where in animals treated with high doses of BPA, the percentage of NRG1-positive neurons amounted to above 45% of all neuronal cells. The mechanisms of observed changes are not entirely clear, but probably result from neurotoxic, neurodegenerative and/or proinflammatory activity of BPA and are protective and adaptive in nature. Full article
(This article belongs to the Special Issue Epigenetic Effects and Toxicity of Environmental Pollutants)
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Review

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24 pages, 2149 KiB  
Review
Pleiotropic Outcomes of Glyphosate Exposure: From Organ Damage to Effects on Inflammation, Cancer, Reproduction and Development
by Marianna Marino, Elena Mele, Andrea Viggiano, Stefania Lucia Nori, Rosaria Meccariello and Antonietta Santoro
Int. J. Mol. Sci. 2021, 22(22), 12606; https://doi.org/10.3390/ijms222212606 - 22 Nov 2021
Cited by 22 | Viewed by 6939
Abstract
Glyphosate is widely used worldwide as a potent herbicide. Due to its ubiquitous use, it is detectable in air, water and foodstuffs and can accumulate in human biological fluids and tissues representing a severe human health risk. In plants, glyphosate acts as an [...] Read more.
Glyphosate is widely used worldwide as a potent herbicide. Due to its ubiquitous use, it is detectable in air, water and foodstuffs and can accumulate in human biological fluids and tissues representing a severe human health risk. In plants, glyphosate acts as an inhibitor of the shikimate pathway, which is absent in vertebrates. Due to this, international scientific authorities have long-considered glyphosate as a compound that has no or weak toxicity in humans. However, increasing evidence has highlighted the toxicity of glyphosate and its formulations in animals and human cells and tissues. Thus, despite the extension of the authorization of the use of glyphosate in Europe until 2022, several countries have begun to take precautionary measures to reduce its diffusion. Glyphosate has been detected in urine, blood and maternal milk and has been found to induce the generation of reactive oxygen species (ROS) and several cytotoxic and genotoxic effects in vitro and in animal models directly or indirectly through its metabolite, aminomethylphosphonic acid (AMPA). This review aims to summarize the more relevant findings on the biological effects and underlying molecular mechanisms of glyphosate, with a particular focus on glyphosate's potential to induce inflammation, DNA damage and alterations in gene expression profiles as well as adverse effects on reproduction and development. Full article
(This article belongs to the Special Issue Epigenetic Effects and Toxicity of Environmental Pollutants)
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