scholarly journals Transgenerational effects in DNA methylation, genotoxicity and reproductive phenotype by chronic arsenic exposure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lydia Enith Nava-Rivera ◽  
Nadia Denys Betancourt-Martínez ◽  
Rodrigo Lozoya-Martínez ◽  
Pilar Carranza-Rosales ◽  
Nancy Elena Guzmán-Delgado ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Life ◽  
Chronic Exposure ◽  
Sperm Quality ◽  
Arsenic Exposure ◽  
Environmental Toxicants ◽  
Reproductive Parameters ◽  
Transgenerational Effects ◽  
Chronic Arsenic Exposure ◽  
Reproductive Phenotype

AbstractAn emerging concern is the influences of early life exposure to environmental toxicants on offspring characteristics in later life. Since recent evidence suggests a transgenerational transference of aberrant phenotypes from exposed-parents to non-exposed offspring related to adult-onset diseases including reproductive phenotype. The transgenerational potential of arsenic a well know genotoxic and epigenetic modifier agent has not been assessed in mammals until now. In this experimental study, we evaluated the transgenerational effects of arsenic in a rat model with chronic exposure to arsenic. Rats chronically exposed to arsenic in drinking water (1 mg As2O3/mL) (F0) were mated to produce the arsenic lineage (F1, F2, and F3). The arsenic toxic effects on were evaluated over the four generations by analyzing the DNA methylation percentage, genotoxicity in WBC and physical and reproductive parameters, including sperm quality parameters and histopathological evaluation of the gonads. Chronic exposure to arsenic caused genotoxic damage (F0–F3) different methylation patterns, alterations in physical and reproductive parameters, aberrant morphology in the ovaries (F0 and F1) and testicles (F1–F3), and a decrease in the quality of sperm (F0–F3, except F2). Parental chronic arsenic exposure causes transgenerational genotoxicity and changes in global DNA methylation which might be associated with reproductive defects in rats. Combined with recent studies reveal that disturbances in the early life of an individual can affect the health of later generations.

Transgenerational inheritance of abnormal spermatogenesis with Igf2/H19 epigenetic alteration in CD1 mouse induced by in utero arsenic exposure

2020 ◽  
Author(s):  
Guoying Yin ◽  
Liting Xia ◽  
Yaxing Hou ◽  
Yaoyan Li ◽  
Deqing Cao ◽  
...  
Keyword(s):  
Sperm Quality ◽  
Methylation Status ◽  
Arsenic Exposure ◽  
Male Offspring ◽  
Control Group ◽  
Environmental Toxicants ◽  
Transgenerational Inheritance ◽  
Developmental Exposure ◽  
Reproductive Disease ◽  
Untreated Female

AbstractDevelopmental exposure to environmental toxicants can induce transgenerational reproductive disease phenotypes through epigenetic mechanisms. However, little is known about the transgenerational effects of arsenic exposure. We hypothesize that prenatal arsenic exposure may result in impaired spermatogenesis in subsequent generations of male mice. To test our hypothesis, we treated pregnant CD-1 (F0) mice with drinking water containing sodium arsenite (85 ppm) from days 8 to 18 of gestation. Male offspring were bred with untreated female mice until the F3 generation was produced. Our results revealed that transient exposure of the F0 gestating female to arsenic can result in decreased sperm quality and histological abnormalities in testes of male offspring in the F1 and F3 generations. The overall methylation status of Igf2 DMR2 and H19 DMR was significantly lower in the arsenic-exposed group than that of the control group in both F1 and F3 generations. The relative mRNA expression levels of Igf2 and H19 in arsenic-exposed males were significantly higher than in the control males in both F1 and F3 generations. This study indicates that ancestral exposure to arsenic may result in transgenerational inheritance of an impaired spermatogenesis phenotyping involving both epigenetic alterations and the abnormal expression of Igf2 and H19.

scholarly journals DNA Methylation Patterns in the Round Goby Hypothalamus Support an On-The-Spot Decision Scenario for Territorial Behavior

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 219 ◽  
Author(s):  
Vincent Somerville ◽  
Michaela Schwaiger ◽  
Philipp E. Hirsch ◽  
Jean-Claude Walser ◽  
Karen Bussmann ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Life ◽  
Life Experiences ◽  
Round Goby ◽  
High Growth ◽  
Neogobius Melanostomus ◽  
Epigenetic Mechanism ◽  
Fish Model ◽  
Methylation Patterns ◽  
Reproductive Phenotype

The question as to how early life experiences are stored on a molecular level and affect traits later in life is highly topical in ecology, medicine, and epigenetics. In this study, we use a fish model to investigate whether DNA methylation mediates early life experiences and predetermines a territorial male reproductive phenotype. In fish, adult reproductive phenotypes frequently depend on previous life experiences and are often associated with distinct morphological traits. DNA methylation is an epigenetic mechanism which is both sensitive to environmental conditions and stably inherited across cell divisions. We therefore investigate early life predisposition in the round goby Neogobius melanostomus by growth back-calculations and then study DNA methylation by MBD-Seq in the brain region controlling vertebrate reproductive behavior, the hypothalamus. We find a link between the territorial reproductive phenotype and high growth rates in the first year of life. However, hypothalamic DNA methylation patterns reflect the current behavioral status independently of early life experiences. Together, our data suggest a non-predetermination scenario in the round goby, in which indeterminate males progress to a non-territorial status in the spawning season, and in which some males then assume a specialized territorial phenotype if current conditions are favorable.

scholarly journals Integrative Analysis of Gene-Specific DNA Methylation and Untargeted Metabolomics Data from the ELEMENT Cohort

2020 ◽  
Vol 13 ◽  
pp. 251686572097788
Author(s):  
Jaclyn M Goodrich ◽  
Emily C Hector ◽  
Lu Tang ◽  
Jennifer L LaBarre ◽  
Dana C Dolinoy ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Life ◽  
Regulatory Networks ◽  
Tanner Stage ◽  
Later Life ◽  
Untargeted Metabolomics ◽  
Environmental Toxicants ◽  
Blood Leukocytes ◽  
Cross Sectional ◽  
Metabolomics Data

Epigenetic modifications, such as DNA methylation, influence gene expression and cardiometabolic phenotypes that are manifest in developmental periods in later life, including adolescence. Untargeted metabolomics analysis provide a comprehensive snapshot of physiological processes and metabolism and have been related to DNA methylation in adults, offering insights into the regulatory networks that influence cellular processes. We analyzed the cross-sectional correlation of blood leukocyte DNA methylation with 3758 serum metabolite features (574 of which are identifiable) in 238 children (ages 8-14 years) from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study. Associations between these features and percent DNA methylation in adolescent blood leukocytes at LINE-1 repetitive elements and genes that regulate early life growth ( IGF2, H19, HSD11B2) were assessed by mixed effects models, adjusting for sex, age, and puberty status. After false discovery rate correction (FDR q < 0.05), 76 metabolites were significantly associated with LINE-1 DNA methylation, 27 with HSD11B2, 103 with H19, and 4 with IGF2. The ten identifiable metabolites included dicarboxylic fatty acids (five associated with LINE-1 or H19 methylation at q < 0.05) and 1-octadecanoyl-rac-glycerol ( q < 0.0001 for association with H19 and q = 0.04 for association with LINE-1). We then assessed the association between these ten known metabolites and adiposity 3 years later. Two metabolites, dicarboxylic fatty acid 17:3 and 5-oxo-7-octenoic acid, were inversely associated with measures of adiposity ( P < .05) assessed approximately 3 years later in adolescence. In stratified analyses, sex-specific and puberty-stage specific (Tanner stage = 2 to 5 vs Tanner stage = 1) associations were observed. Most notably, hundreds of statistically significant associations were observed between H19 and LINE-1 DNA methylation and metabolites among children who had initiated puberty. Understanding relationships between subclinical molecular biomarkers (DNA methylation and metabolites) may increase our understanding of genes and biological pathways contributing to metabolic changes that underlie the development of adiposity during adolescence.

scholarly journals Gene-Specific Differential DNA Methylation and Chronic Arsenic Exposure in an Epigenome-Wide Association Study of Adults in Bangladesh

2015 ◽  
Vol 123 (1) ◽  
pp. 64-71 ◽  
Author(s):  
Maria Argos ◽  
Lin Chen ◽  
Farzana Jasmine ◽  
Lin Tong ◽  
Brandon L. Pierce ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Association Study ◽  
Arsenic Exposure ◽  
Chronic Arsenic Exposure

scholarly journals DNA methylation patterns in the round goby hypothalamus support an on-the-spot decision scenario for territorial behaviour

2018 ◽  
Author(s):  
Irene Adrian-Kalchhauser ◽  
Vincent Somerville ◽  
Michaela Schwaiger ◽  
Philipp Hirsch ◽  
Karen Bussmann ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Life ◽  
Life Experiences ◽  
Round Goby ◽  
High Growth ◽  
Reproductive Behaviour ◽  
Neogobius Melanostomus ◽  
Epigenetic Mechanism ◽  
Methylation Patterns ◽  
Reproductive Phenotype

How early life experiences are stored on a molecular level and affect behavioural phenotypes later in life is not well understood. In fish, reproductive phenotypes are often easily discernible and frequently depend on previous life experiences. DNA methylation is an epigenetic mechanism which is both sensitive to environmental conditions and stable across cell divisions. In this study, we therefore investigate whether DNA methylation mediates early life experiences and predetermines the territorial male reproductive phenotype in the round goby, Neogobius melanostomus. We investigate early life predisposition by growth back-calculations and then study DNA methylation by MBD-Seq in the round goby hypothalamus as the brain region controlling vertebrate reproductive behaviour. We find that the territorial reproductive phenotype is linked to a high growth rate in the first year of life. Hypothalamic DNA methylation patterns, however, reflect the current behavioural status independently of early life experiences. Together, our data suggest a non-predetermination scenario in which indeterminate males progress to a non-territorial status in the spawning season, and in which some males then assume a specialized territorial phenotype if current conditions are favourable.

scholarly journals Early-Life Exposure to Environmental Contaminants Perturbs the Sperm Epigenome and Induces Negative Pregnancy Outcomes for Three Generations via the Paternal Lineage

Epigenomes ◽  
2021 ◽  
Vol 5 (2) ◽  
pp. 10
Author(s):  
Clotilde Maurice ◽  
Mathieu Dalvai ◽  
Romain Lambrot ◽  
Astrid Deschênes ◽  
Marie-Pier Scott-Boyer ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Pregnancy Outcomes ◽  
Sperm Quality ◽  
The Arctic ◽  
Congenital Defects ◽  
Developmental Defects ◽  
Early Life Exposure ◽  
Sperm Dna ◽  
Inuit Population ◽  
Sperm Dna Methylation

Due to the grasshopper effect, the Arctic food chain in Canada is contaminated with persistent organic pollutants (POPs) of industrial origin, including polychlorinated biphenyls and organochlorine pesticides. Exposure to POPs may be a contributor to the greater incidence of poor fetal growth, placental abnormalities, stillbirths, congenital defects and shortened lifespan in the Inuit population compared to non-Aboriginal Canadians. Although maternal exposure to POPs is well established to harm pregnancy outcomes, paternal transmission of the effects of POPs is a possibility that has not been well investigated. We used a rat model to test the hypothesis that exposure to POPs during gestation and suckling leads to developmental defects that are transmitted to subsequent generations via the male lineage. Indeed, developmental exposure to an environmentally relevant Arctic POPs mixture impaired sperm quality and pregnancy outcomes across two subsequent, unexposed generations and altered sperm DNA methylation, some of which are also observed for two additional generations. Genes corresponding to the altered sperm methylome correspond to health problems encountered in the Inuit population. These findings demonstrate that the paternal methylome is sensitive to the environment and that some perturbations persist for at least two subsequent generations. In conclusion, although many factors influence health, paternal exposure to contaminants plays a heretofore-underappreciated role with sperm DNA methylation contributing to the molecular underpinnings involved.

scholarly journals Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer

2021 ◽  
Author(s):  
Mayukh Banerjee ◽  
Ana Ferragut Cardoso ◽  
Laila Al-Eryani ◽  
Jianmin Pan ◽  
Theodore S. Kalbfleisch ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Mrna Expression ◽  
Hacat Cell ◽  
Arsenic Exposure ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Mesenchymal Transition ◽  
Chronic Arsenic Exposure ◽  
Pathway Analyses ◽  
Time Point

AbstractChronic arsenic exposure causes skin cancer, although the underlying molecular mechanisms are not well defined. Altered microRNA and mRNA expression likely play a pivotal role in carcinogenesis. Changes in genome-wide differential expression of miRNA and mRNA at 3 strategic time points upon chronic sodium arsenite (As3+) exposure were investigated in a well-validated HaCaT cell line model of arsenic-induced cutaneous squamous cell carcinoma (cSCC). Quadruplicate independent HaCaT cell cultures were exposed to 0 or 100 nM As3+ for up to 28-weeks (wk). Cell growth was monitored throughout the course of exposure and epithelial-mesenchymal transition (EMT) was examined employing immunoblot. Differentially expressed miRNA and mRNA profiles were generated at 7, 19, and 28-wk by RNA-seq, followed by identification of differentially expressed mRNA targets of differentially expressed miRNAs through expression pairing at each time point. Pathway analyses were performed for total differentially expressed mRNAs and for the miRNA targeted mRNAs at each time point. RNA-seq predictions were validated by immunoblot of selected target proteins. While the As3+-exposed cells grew slower initially, growth was equal to that of unexposed cells by 19-wk (transformation initiation), and exposed cells subsequently grew faster than passage-matched unexposed cells. As3+-exposed cells had undergone EMT at 28-wk. Pathway analyses demonstrate dysregulation of carcinogenesis-related pathways and networks in a complex coordinated manner at each time point. Immunoblot data largely corroborate RNA-seq predictions in the endoplasmic reticulum stress (ER stress) pathway. This study provides a detailed molecular picture of changes occurring during the arsenic-induced transformation of human keratinocytes.

scholarly journals Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cristian Carmeli ◽  
Zoltán Kutalik ◽  
Pashupati P. Mishra ◽  
Eleonora Porcu ◽  
Cyrille Delpierre ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Regulation ◽  
Cohort Studies ◽  
Early Life ◽  
Life Experiences ◽  
Socioeconomic Disadvantage ◽  
Mediating Role ◽  
The Impact ◽  
The Relationship

AbstractIndividuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.

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