Environmental Epigenetics最新文献

{"title":"A new approach to study stochastic epigenetic mutations in sperm methylome of Vietnam war veterans directly exposed to Agent Orange.","authors":"Luigi Corsaro, Davide Sacco, Carlo Corbetta, Davide Gentilini, Alice Faversani, Fulvio Ferrara, Lucy Costantino","doi":"10.1093/eep/dvae020","DOIUrl":"10.1093/eep/dvae020","url":null,"abstract":"<p><p>Among the various environmental pollutants, dioxin, a highly toxic and widely used compound, is associated with numerous adverse health effects, including a potentially toxic multigenerational effect. Understanding the mechanisms by which dioxin exposure can affect sperm epigenetics is critical to comprehending the potential consequences for offspring health and development. This study investigates the possible association between weighted epimutations, hypothesized as markers of epigenetic drift, and dioxin exposure in sperm tissues. We used a public online methylation dataset consisting of 37 participants: 26 Vietnam veterans exposed to Agent Orange, an herbicide contaminated with 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (TCDD), and 11 individuals not directly exposed to TCDD but whose serum dioxin levels are equivalent to the background. In our study, conducted at the gene level, 437 epimutated genes were identified as significantly associated with each single-digit increase in serum dioxin levels. We found no significant association between the rise in total epimutation load and serum dioxin levels. The pathway analysis performed on the genes reveals biological processes mainly related to changes in embryonic morphology, development, and reproduction. Results from our current study suggest the importance of further investigations on the consequences of dioxin exposure in humans with specific reference to germinal tissue and related heredity.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae020"},"PeriodicalIF":4.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intercontinental insights into autism spectrum disorder: a synthesis of environmental influences and DNA methylation.","authors":"George E Kuodza, Ray Kawai, Janine M LaSalle","doi":"10.1093/eep/dvae023","DOIUrl":"https://doi.org/10.1093/eep/dvae023","url":null,"abstract":"<p><p>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by a broad range of symptoms. The etiology of ASD is thought to involve complex gene-environment interactions, which are crucial to understanding its various causes and symptoms. DNA methylation is an epigenetic mechanism that potentially links genetic predispositions to environmental factors in the development of ASD. This review provides a global perspective on ASD, focusing on how DNA methylation studies may reveal gene-environment interactions characteristic of specific geographical regions. It delves into the role of DNA methylation in influencing the causes and prevalence of ASD in regions where environmental influences vary significantly. We also address potential explanations for the high ASD prevalence in North America, considering lifestyle factors, environmental toxins, and diagnostic considerations. Asian and European studies offer insights into endocrine-disrupting compounds, persistent organic pollutants, maternal smoking, and their associations with DNA methylation alterations in ASD. In areas with limited data on DNA methylation and ASD, such as Africa, Oceania, and South America, we discuss prevalent environmental factors based on epidemiological studies. Additionally, the review integrates global and country-specific prevalence data from various studies, providing a comprehensive picture of the variables influencing ASD diagnoses over region and year of assessment. This prevalence data, coupled with regional environmental variables and DNA methylation studies, provides a perspective on the complexities of ASD research. Integrating global prevalence data, we underscore the need for a comprehensive global understanding of ASD's complex etiology. Expanded research into epigenetic mechanisms of ASD is needed, particularly in underrepresented populations and locations, to enhance biomarker development for diagnosis and intervention strategies for ASD that reflect the varied environmental and genetic landscapes worldwide.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae023"},"PeriodicalIF":4.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic biomarker for preeclampsia-associated preterm birth and potential preventative medicine.","authors":"Eric E Nilsson, Paul Winchester, Cathy Proctor, Daniel Beck, Michael K Skinner","doi":"10.1093/eep/dvae022","DOIUrl":"10.1093/eep/dvae022","url":null,"abstract":"<p><p>Preterm birth (PTB) has dramatically increased within the population (i.e. >10%) and preeclampsia is a significant sub-category of PTB. Currently, there are no practical clinical parameters or biomarkers which predict preeclampsia induced PTB. The current study investigates the potential use of epigenetic (DNA methylation) alterations as a maternal preeclampsia biomarker. Non-preeclampsia term births were compared to preeclampsia PTBs to identify DNA methylation differences (i.e. potential epigenetic biomarker). Maternal buccal cell cheek swabs were used as a marker cell for systemic epigenetic alterations in the individuals, which are primarily due to environmentally induced early life or previous generations impacts, and minimally impacted or associated with the disease etiology or gestation variables. A total of 389 differential DNA methylation regions (DMRs) were identified and associated with the presence of preeclampsia. The DMRs were genome-wide and were predominantly low CpG density (<2 CpG/100 bp). In comparison with a previous PTB buccal cell epigenetic biomarker there was a 15% (60 DMR) overlap, indicating that the majority of the DMRs are unique for preeclampsia. Few previously identified preeclampsia genes have been identified, however, the DMRs had gene associations in the P13 K-Akt signaling pathway and metabolic gene family, such as phospholipid signaling pathway. Preliminary validation of the DMR use as a potential maternal biomarker used a cross-validation analysis on the samples and provided 78% accuracy. Although prospective expanded clinical trials in first trimester pregnancies and clinical comparisons are required, the current study provides the potential proof of concept a preeclampsia epigenetic biomarker may exist. The availability of a preeclampsia PTB maternal susceptibility biomarker may facilitate clinical management and allow preventative medicine approaches to identify and treat the preeclampsia condition prior to its occurrence.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae022"},"PeriodicalIF":4.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal mitochondrial DNA copy number and methylation as possible predictors of pregnancy outcomes in a Michigan pregnancy cohort.","authors":"Maria E Cinzori, Megan Nicol, Alisa L Dewald, Jaclyn M Goodrich, Zheng Zhou, Joseph C Gardiner, Jean M Kerver, Dana C Dolinoy, Nicole Talge, Rita S Strakovsky","doi":"10.1093/eep/dvae021","DOIUrl":"10.1093/eep/dvae021","url":null,"abstract":"<p><p>Little is understood about the roles of mitochondria in pregnancy-related adaptations. Therefore, we evaluated associations of maternal early-to-mid pregnancy mitochondrial DNA copy number (mtDNAcn) and mtDNA methylation with birth size and gestational length. Michigan women (<i>n</i> = 396) provided venous bloodspots at median 11 weeks gestation to quantify mtDNAcn marker NADH-ubiquinone oxidoreductase chain 1 (<i>ND1</i>) using real-time quantitative PCR and mtDNA methylation at several regions within four mitochondria-specific genes using pyrosequencing: <i>MTTF</i> (mitochondrially encoded tRNA phenylalanine), <i>DLOOP</i> (D-loop promoter region, heavy strand), <i>CYTB</i> (cytochrome b), and <i>LDLR</i> (D-loop promoter region, light strand). We abstracted gestational length and birthweight from birth certificates and calculated birthweight <i>z</i>-scores using published references. We used multivariable linear regression to evaluate associations of mtDNAcn and mtDNA methylation with birthweight and birthweight <i>z</i>-scores. Cox Proportional Hazards Models (PHMs) and quantile regression characterized associations of mitochondrial measures with gestational length. We also considered differences by fetal sex. Using linear regression and Cox PHMs, mtDNAcn was not associated with birth outcomes, whereas associations of mtDNA methylation with birth outcomes were inconsistent. However, using quantile regression, mtDNAcn was associated with shorter gestation in female newborns at the upper quantiles of gestational length, but with longer gestational length in males at the lower quantiles of gestational length. Maternal <i>LDLR, DLOOP</i>, and <i>MTTF</i> methylation was associated with longer gestational length in females at the upper quantiles and in males at lower gestational length quantiles. Maternal mtDNAcn and mtDNA methylation were associated with gestational length in babies born comparatively early or late, which could reflect adaptations in mitochondrial processes that regulate the length of gestation.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae021"},"PeriodicalIF":4.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EV-miRNA associated with environmental air pollution exposures in the MADRES cohort.","authors":"Helen Bermudez Foley, Sandrah P Eckel, Tingyu Yang, Mario Vigil, Xinci Chen, Carmen Marsit, Shohreh F Farzan, Theresa M Bastain, Rima Habre, Carrie V Breton","doi":"10.1093/eep/dvae019","DOIUrl":"10.1093/eep/dvae019","url":null,"abstract":"<p><p>Air pollution is a hazardous contaminant, exposure to which has substantial consequences for health during critical periods, such as pregnancy. MicroRNA (miRNA) is an epigenetic mechanism that modulates transcriptome responses to the environment and has been found to change in reaction to air pollution exposure. The data are limited regarding extracellular-vesicle (EV) miRNA variation associated with air pollution exposure during pregnancy and in susceptible populations who may be disproportionately exposed. This study aimed to identify EV-miRNA expression associated with ambient, residential exposure to PM_2.5, PM₁₀, NO₂, O₃ and with traffic-related NO_x in 461 participants of the MADRES cohort, a low income, predominantly Hispanic pregnancy cohort based in Los Angeles, CA. This study used residence-based modeled air pollution data as well as Nanostring panels for EVmiRNA extracted with Qiagen exoRNeasy kits to evaluate 483 miRNA in plasma in early and late pregnancy. Average air pollution exposures were considered separately for 1-day, 1-week, and 8-week windows before blood collection in both early and late pregnancy. This study identified 63 and 66 EV-miRNA significantly associated with PM_2.5 and PM₁₀, respectively, and 2 miRNA associated with traffic-related NO_X (False Discovery Rate-adjusted <i>P</i>-value < .05). Of 103 unique EV-miRNA associated with PM, 92% were associated with lung conditions according to HMDD (Human miRNA Disease Database) evidence. In particular, EV-miRNA previously identified with air pollution exposure also associated with PM_2.5 and PM₁₀ in this study were: miR-126, miR-16-5p, miR-187-3p, miR200b-3p, miR486-3p, and miR-582-3p. There were no significant differences in average exposures in early vs late pregnancy. Significant EV-miRNAs were only identified in late pregnancy with an 8-week exposure window, suggesting a vulnerable timeframe of exposure, rather than an acute response. These results describe a wide array of EV-miRNA for which expression is affected by PM exposure and may be in part mediating the biological response to ambient air pollution, with potential for health implications in pregnant women and their children.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae019"},"PeriodicalIF":4.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: To live or let die? Epigenetic adaptations to climate change-a review.","authors":"","doi":"10.1093/eep/dvae016","DOIUrl":"https://doi.org/10.1093/eep/dvae016","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/eep/dvae009.].</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae016"},"PeriodicalIF":4.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation correlates with transcriptional noise in response to elevated pCO₂ in the eastern oyster (<i>Crassostrea virginica</i>).","authors":"Yaamini R Venkataraman, Ariana S Huffmyer, Samuel J White, Alan Downey-Wall, Jill Ashey, Danielle M Becker, Zachary Bengtsson, Hollie M Putnam, Emma Strand, Javier A Rodríguez-Casariego, Shelly A Wanamaker, Katie E Lotterhos, Steven B Roberts","doi":"10.1093/eep/dvae018","DOIUrl":"10.1093/eep/dvae018","url":null,"abstract":"<p><p>Ocean acidification significantly affects marine calcifiers like oysters, warranting the study of molecular mechanisms like DNA methylation that contribute to adaptive plasticity in response to environmental change. However, a consensus has not been reached on the extent to which methylation modules gene expression, and in turn plasticity, in marine invertebrates. In this study, we investigated the impact of pCO₂ on gene expression and DNA methylation in the eastern oyster, <i>Crassostrea virginica</i>. After a 30-day exposure to control (572 ppm) or elevated pCO₂ (2827 ppm), whole-genome bisulfite sequencing (WGBS) and RNA-seq data were generated from adult female gonad tissue and male sperm samples. Although differentially methylated loci (DMLs) were identified in females (89) and males (2916), there were no differentially expressed genes and only one differentially expressed transcript in females. However, gene body methylation impacted other forms of gene activity in sperm, such as the maximum number of transcripts expressed per gene and changes in the predominant transcript expressed. Elevated pCO₂ exposure increased gene expression variability (transcriptional noise) in males but decreased noise in females, suggesting a sex-specific role of methylation in gene expression regulation. Functional annotation of genes with changes in transcript-level expression or containing DMLs revealed several enriched biological processes potentially involved in elevated pCO₂ response, including apoptotic pathways and signal transduction, as well as reproductive functions. Taken together, these results suggest that DNA methylation may regulate gene expression variability to maintain homeostasis in elevated pCO₂ conditions and could play a key role in environmental resilience in marine invertebrates.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae018"},"PeriodicalIF":4.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bronchial cell epigenetic aging in a human experimental study of short-term diesel and ozone exposures.","authors":"Jamaji C Nwanaji-Enwerem, Anne K Bozack, Cavin Ward-Caviness, David Diaz-Sanchez, Robert B Devlin, Marie-Abèle C Bind, Andres Cardenas","doi":"10.1093/eep/dvae017","DOIUrl":"10.1093/eep/dvae017","url":null,"abstract":"<p><p>Blood-based, observational, and cross-sectional epidemiological studies suggest that air pollutant exposures alter biological aging. In a single-blinded randomized crossover human experiment of 17 volunteers, we examined the effect of randomized 2-h controlled air pollution exposures on respiratory tissue epigenetic aging. Bronchial epithelial cell DNA methylation 24 h post-exposure was measured using the HumanMethylation450K BeadChip, and there was a minimum 2-week washout period between exposures. All 17 volunteers were exposed to ozone, but only 13 were exposed to diesel exhaust. Horvath DNAmAge [Pearson coefficient (r) = 0.64; median absolute error (MAE) = 2.7 years], GrimAge (r = 0.81; MAE = 13 years), and DNAm Telomere Length (DNAmTL) (r = -0.65) were strongly correlated with chronological age in this tissue. Compared to clean air, ozone exposure was associated with longer DNAmTL (median difference 0.11 kb, Fisher's exact <i>P</i>-value = .036). This randomized trial suggests a weak relationship of ozone exposure with DNAmTL in target respiratory cells. Still, causal relationships with long-term exposures need to be evaluated.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae017"},"PeriodicalIF":4.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal exposure to maternal smoking and adult lung cancer risk: a nested case-control study using peripheral blood leukocyte DNA methylation prediction of exposure.","authors":"Meng Ru, Dominique S Michaud, Naisi Zhao, Karl T Kelsey, Devin C Koestler, Jiayun Lu, Elizabeth A Platz, Christine M Ladd-Acosta","doi":"10.1093/eep/dvae015","DOIUrl":"10.1093/eep/dvae015","url":null,"abstract":"<p><p>A prior study reported no association between prenatal smoking methylation scores and adult lung cancer risk adjusting for methylation-predicted adult smoking, without considering maternal smoking trends by birth cohort. To address this gap, we examined the association between prenatal smoking methylation scores and adult lung cancer, independent of methylation-predicted adult packyears and by birth cohort, in a study nested in CLUE II. Included were 208 incident lung cancer cases ascertained by cancer registry linkage and 208 controls matched on age, sex, and smoking. DNA methylation was measured in prediagnostic blood. We calculated two prenatal smoking scores, using 19 (Score-19) and 15 (Score-15) previously identified CpGs and a methylation-predicted adult packyears score. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for adult packyears score and batch effects. Score-15 was positively associated with lung cancer (per standard deviation, OR = 1.40, 95% CI = 1.10-1.79, <i>P</i>-trend = .006), especially in the 1930-1938 birth cohort (OR = 3.43, 95% CI = 1.55-7.60, <i>P</i>-trend = .002). Score-19 was associated only in the 1930-1938 birth cohort (OR = 2.12, 95% CI = 1.15-3.91). Participants with both prenatal scores below the median (vs all other combinations) had lower risk (OR = 0.44, 95% CI = 0.27-0.72), especially in the 1930-1938 birth cohort (OR = 0.16, 95% CI = 0.04-0.62). Among ever smokers, participants with higher prenatal smoking scores had higher risk, irrespective of adult packyears (low: OR = 2.81, 95% CI = 1.38-5.72, high: OR = 2.67, 95% CI = 1.03-6.95). This prospective study suggests a positive association between prenatal smoking exposure and adult lung cancer risk, especially in the 1930-1938 birth cohort, independent of active smoking. Future studies with multiple birth cohorts are needed.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae015"},"PeriodicalIF":4.8,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic transgenerational inheritance of toxicant exposure-specific non-coding RNA in sperm.","authors":"Hayden McSwiggin, Rubens Magalhães, Eric E Nilsson, Wei Yan, Michael K Skinner","doi":"10.1093/eep/dvae014","DOIUrl":"10.1093/eep/dvae014","url":null,"abstract":"<p><p>Environmentally induced epigenetic transgenerational inheritance of phenotypic variation and disease susceptibility requires the germ cell (sperm or egg) transmission of integrated epigenetic mechanisms involving DNA methylation, histone modifications, and non-coding RNA (ncRNA) actions. Previous studies have demonstrated that transgenerational exposure and disease-specific differential DNA methylation regions (DMRs) in sperm are observed and that ncRNA-mediated DNA methylation occurs. The current study was designed to determine if transgenerational exposure-specific ncRNAs exist in sperm. Specifically, toxicants with distinct mechanisms of action including the fungicide vinclozolin (anti-androgenic), pesticide dichlorodiphenyltrichloroethane (estrogenic), herbicide atrazine (endocrine disruptor at cyclic adenosine monophosphate level), and hydrocarbon mixture jet fuel (JP8) (aryl hydrocarbon receptor disruptor) were used to promote transgenerational disease phenotypes in F3 generation outbred rats. New aliquots of sperm, previously collected and used for DNA methylation analyses, were used in the current study for ncRNA sequencing analyses of nuclear RNA. Significant changes in transgenerational sperm ncRNA were observed for each transgenerational exposure lineage. The majority of ncRNA was small noncoding RNAs including piwi-interacting RNA, tRNA-derived small RNAs, microRNAs, rRNA-derived small RNA, as well as long ncRNAs. Although there was some overlap among the different classes of ncRNA across the different exposures, the majority of differentially expressed ncRNAs were exposure-specific with no overlapping ncRNA between the four different exposure lineages in the transgenerational F3 generation sperm nuclear ncRNAs. The ncRNA chromosomal locations and gene associations were identified for a small number of differential expressed ncRNA. Interestingly, an overlap analysis between the transgenerational sperm DMRs and ncRNA chromosomal locations demonstrated small populations of overlapping ncRNA, but a large population of non-overlapping ncRNAs. Observations suggest that transgenerational sperm ncRNAs have both exposure-specific populations within the different classes of ncRNA, as well as some common populations of ncRNAs among the different exposures. The lack of co-localization of many of the ncRNAs with previously identified transgenerational DMRs suggests a distal integration of the different epigenetic mechanisms. The potential use of ncRNA analyses for transgenerational toxicant exposure assessment appears feasible.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae014"},"PeriodicalIF":4.8,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}