Meng Ru, Dominique S Michaud, Naisi Zhao, Karl T Kelsey, Devin C Koestler, Jiayun Lu, Elizabeth A Platz, Christine M Ladd-Acosta
{"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":4.3,"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}
Hayden McSwiggin, Rubens Magalhães, Eric E Nilsson, Wei Yan, Michael K Skinner
{"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}
Elizabeth A Mojica, Kathleen A Petcu, Dietmar Kültz
{"title":"Environmental conditions elicit a slow but enduring response of histone post-translational modifications in Mozambique tilapia.","authors":"Elizabeth A Mojica, Kathleen A Petcu, Dietmar Kültz","doi":"10.1093/eep/dvae013","DOIUrl":"10.1093/eep/dvae013","url":null,"abstract":"<p><p>This study sheds new light on the timescale through which histone post-translational modifications (PTMs) respond to environmental stimuli, demonstrating that the histone PTM response does not necessarily precede the proteomic response or acclimation. After a variety of salinity treatments were administered to Mozambique tilapia (<i>Oreochromis mossambicus</i>) throughout their lifetimes, we quantified 343 histone PTMs in the gills of each fish. We show here that histone PTMs differ dramatically between fish exposed to distinct environmental conditions for 18 months, and that the majority of these histone PTM alterations persist for at least 4 weeks, irrespective of further salinity changes. However, histone PTMs respond minimally to 4-week-long periods of salinity acclimation during adulthood. The results of this study altogether signify that patterns of histone PTMs in individuals reflect their prolonged exposure to environmental conditions.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae013"},"PeriodicalIF":4.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380314","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}
Juliann A Jugan, Kyle B Jackson, Sarah E Elmore, Michele A La Merrill
{"title":"Impaired energy expenditure following exposure to either DDT or DDE in mice may be mediated by DNA methylation changes in brown adipose.","authors":"Juliann A Jugan, Kyle B Jackson, Sarah E Elmore, Michele A La Merrill","doi":"10.1093/eep/dvae011","DOIUrl":"10.1093/eep/dvae011","url":null,"abstract":"<p><p>The insecticide dichlorodiphenyltrichloroethane (DDT) and its persistent metabolite, dichlorodiphenyldichloroethylene (DDE), have been associated with increased adiposity and obesity in multiple generations of rodents and humans. These lipophilic pollutants accumulate in adipose tissue and appear to decrease energy expenditure through the impairment of thermogenesis in brown adipose tissue (BAT). We hypothesized that impaired thermogenesis is due to persistent epigenetic modifications of BAT. To address this, we exposed C57BL/6 J mice to DDT or DDE from gestational day (GD) 11.5 to postnatal day (PND) 5, evaluated longitudinal body temperature, and performed reduced representation bisulfite sequencing and RNA sequencing of BAT from infant and adult offspring. Exposure to DDT or DDE reduced core body temperature in adult mice, and differential methylation at the pathway and gene level was persistent from infancy to adulthood. Furthermore, thermogenesis and biological pathways essential for thermogenic function, such as oxidative phosphorylation and mechanistic target of rapamycin kinase (mTOR) signaling, were enriched with differential methylation and RNA transcription in adult mice exposed to DDT or DDE. PAZ6 human brown preadipocytes were differentiated in the presence of DDT or DDE to understand the brown adipocyte-autonomous effect of these pollutants. <i>In vitro</i> exposure led to limited changes in RNA expression; however, mitochondrial membrane potential was decreased <i>in vitro</i> with 0.1 µM and 1 µM doses of DDT or DDE. These results demonstrate that concentrations of DDT and DDE relevant to human exposure have a significant effect on thermogenesis, the transcriptome, and DNA methylome of mouse BAT and the mitochondrial function of human brown adipocytes.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae011"},"PeriodicalIF":4.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460873","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":"To live or let die? Epigenetic adaptations to climate change-a review.","authors":"Jonas Zetzsche, Manon Fallet","doi":"10.1093/eep/dvae009","DOIUrl":"10.1093/eep/dvae009","url":null,"abstract":"<p><p>Anthropogenic activities are responsible for a wide array of environmental disturbances that threaten biodiversity. Climate change, encompassing temperature increases, ocean acidification, increased salinity, droughts, and floods caused by frequent extreme weather events, represents one of the most significant environmental alterations. These drastic challenges pose ecological constraints, with over a million species expected to disappear in the coming years. Therefore, organisms must adapt or face potential extinctions. Adaptations can occur not only through genetic changes but also through non-genetic mechanisms, which often confer faster acclimatization and wider variability ranges than their genetic counterparts. Among these non-genetic mechanisms are epigenetics defined as the study of molecules and mechanisms that can perpetuate alternative gene activity states in the context of the same DNA sequence. Epigenetics has received increased attention in the past decades, as epigenetic mechanisms are sensitive to a wide array of environmental cues, and epimutations spread faster through populations than genetic mutations. Epimutations can be neutral, deleterious, or adaptative and can be transmitted to subsequent generations, making them crucial factors in both long- and short-term responses to environmental fluctuations, such as climate change. In this review, we compile existing evidence of epigenetic involvement in acclimatization and adaptation to climate change and discuss derived perspectives and remaining challenges in the field of environmental epigenetics. <b>Graphical Abstract</b>.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae009"},"PeriodicalIF":4.8,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975419","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}
Alejandra Manjarres-Suarez, Anne Bozack, Andres Cardenas, Jesus Olivero-Verbel
{"title":"DNA methylation is associated with hair trace elements in female adolescents from two vulnerable populations in the Colombian Caribbean.","authors":"Alejandra Manjarres-Suarez, Anne Bozack, Andres Cardenas, Jesus Olivero-Verbel","doi":"10.1093/eep/dvae008","DOIUrl":"10.1093/eep/dvae008","url":null,"abstract":"<p><p>Exposure to trace elements (TEs) influences DNA methylation patterns, which may be associated with disease development. Vulnerable populations, such as adolescents undergoing maturity, are susceptible to the effects of TE exposure. The aim of this study was to analyze the association of hair TE concentration with DNA methylation in a sample from female adolescents living in two communities in the Colombian Caribbean coast. Hair and blood samples were obtained from 45 females, between 13 and 16 years of age. Seventeen TEs were quantified in hair samples. DNA methylation was measured in leukocytes using the Infinium MethylationEPIC BeadChip. Linear models were employed to identify differentially methylated positions (DMPs) adjusting for age, body mass index, mother's education, and cell type composition. Among the tested elements, vanadium, chromium, nickel, copper, zinc, yttrium, tin, and barium were significantly associated with DMPs (false discovery rate < 0.05), registering 225, 1, 2, 184, 1, 209 189, and 104 hits, respectively. Most of the DMPs were positively associated with TEs and located in open sea regions. The greatest number of DMPs was annotated to the <i>HOXA3</i> and <i>FOXO3</i> genes, related to regulation of gene expression and oxidative stress, respectively. These findings suggest that DNA methylation may be involved in linking exposure to TEs among female adolescents to downstream health risks.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae008"},"PeriodicalIF":4.8,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617190","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 and gene therapy in human and veterinary medicine.","authors":"Eva Bártová","doi":"10.1093/eep/dvae006","DOIUrl":"10.1093/eep/dvae006","url":null,"abstract":"<p><p>Gene therapy is a focus of interest in both human and veterinary medicine, especially in recent years due to the potential applications of CRISPR/Cas9 technology. Another relatively new approach is that of epigenetic therapy, which involves an intervention based on epigenetic marks, including DNA methylation, histone post-translational modifications, and post-transcription modifications of distinct RNAs. The epigenome results from enzymatic reactions, which regulate gene expression without altering DNA sequences. In contrast to conventional CRISP/Cas9 techniques, the recently established methodology of epigenetic editing mediated by the CRISPR/dCas9 system is designed to target specific genes without causing DNA breaks. Both natural epigenetic processes and epigenetic editing regulate gene expression and thereby contribute to maintaining the balance between physiological functions and pathophysiological states. From this perspective, knowledge of specific epigenetic marks has immense potential in both human and veterinary medicine. For instance, the use of epigenetic drugs (chemical compounds with therapeutic potential affecting the epigenome) seems to be promising for the treatment of cancer, metabolic, and infectious diseases. Also, there is evidence that an epigenetic diet (nutrition-like factors affecting epigenome) should be considered as part of a healthy lifestyle and could contribute to the prevention of pathophysiological processes. In summary, epigenetic-based approaches in human and veterinary medicine have increasing significance in targeting aberrant gene expression associated with various diseases. In this case, CRISPR/dCas9, epigenetic targeting, and some epigenetic nutrition factors could contribute to reversing an abnormal epigenetic landscape to a healthy physiological state.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae006"},"PeriodicalIF":4.3,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944540","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}
William C Weston, Marie Abèle Bind, Wayne E Cascio, Robert B Devlin, David Diaz-Sanchez, Cavin K Ward-Caviness
{"title":"Accelerated aging and altered subclinical response to ozone exposure in young, healthy adults.","authors":"William C Weston, Marie Abèle Bind, Wayne E Cascio, Robert B Devlin, David Diaz-Sanchez, Cavin K Ward-Caviness","doi":"10.1093/eep/dvae007","DOIUrl":"10.1093/eep/dvae007","url":null,"abstract":"<p><p>Ozone exposure induces a myriad of adverse cardiopulmonary outcomes in humans. Although advanced age and chronic disease are factors that may exacerbate a person's negative response to ozone exposure, there are no molecular biomarkers of susceptibility. Here, we examine whether epigenetic age acceleration (EAA) is associated with responsiveness to short-term ozone exposure. Using data from a crossover-controlled exposure study (<i>n</i> = 17), we examined whether EAA, as measured in lung epithelial cells collected 24 h after clean air exposure, modifies the observed effect of ozone on autonomic function, cardiac electrophysiology, hemostasis, pulmonary function, and inflammation. EAA was assessed in lung epithelial cells extracted from bronchoalveolar lavage fluids, using the pan-tissue aging clock. We used two analytic approaches: (i) median regression to estimate the association between EAA and the estimated risk difference for subclinical responses to ozone and (ii) a block randomization approach to estimate EAA's effect modification of subclinical responses. For both approaches, we calculated Fisher-exact <i>P</i>-values, allowing us to bypass large sample size assumptions. In median regression analyses, accelerated epigenetic age modified associations between ozone and heart rate-corrected QT interval (QTc) ([Formula: see text]= 0.12, <i>P</i>-value = 0.007) and between ozone and C-reactive protein ([Formula: see text] = -0.18, <i>P</i> = 0.069). During block randomization, the directions of association remained consistent for QTc and C-reactive protein; however, the <i>P</i>-values weakened. Block randomization also revealed that responsiveness of plasminogen activator inhibitor-1 (PAI-1) to ozone exposure was modified by accelerated epigenetic aging (PAI-1 difference between accelerated aging-defined block groups = -0.54, <i>P</i>-value = 0.039). In conclusion, EAA is a potential biomarker for individuals with increased susceptibility to ozone exposure even among young, healthy adults.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae007"},"PeriodicalIF":4.8,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283292","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}
Leonard C Steg, Ellen Jaspers, Anar Alshanbayeva, Rodrigo G Arzate-Meija, Maria A Dimitriu, Katharina Gapp, Lola M Kourouma, Kerem Uzel, Isabelle M Mansuy
{"title":"Symposium summary: epigenetic inheritance-impact for biology and society 23-25 August 2023, Zürich, Switzerland.","authors":"Leonard C Steg, Ellen Jaspers, Anar Alshanbayeva, Rodrigo G Arzate-Meija, Maria A Dimitriu, Katharina Gapp, Lola M Kourouma, Kerem Uzel, Isabelle M Mansuy","doi":"10.1093/eep/dvae002","DOIUrl":"https://doi.org/10.1093/eep/dvae002","url":null,"abstract":"<p><p>The possibility that acquired traits can be transmitted across generations has been the subject of intense research in the past decades. This biological process is of major interest to many scientists and has profound implications for biology and society but has complex mechanisms and is therefore challenging to study. Because it involves factors independent from the DNA sequence, this form of heredity is classically referred to as epigenetic inheritance. Many studies have examined how life experiences and various environmental factors can cause phenotypes that are heritable and be manifested in subsequent generations. Recognizing the major importance and complexity of this research, the fourth edition of the Epigenetic Inheritance Symposium Zürich brought together experts from diverse disciplines to address current questions in the field of epigenetic inheritance and present recent findings. The symposium had sessions dedicated to epidemiological evidence and animal models, transmission mechanisms, methodologies and the far-reaching impact on society and evolution. This report summarizes the talks of speakers and describes additional activities offered during the symposium including poster sessions and an art competition on the topic of epigenetic inheritance.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae002"},"PeriodicalIF":3.8,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143035","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":"Characterization of genomic regions escaping epigenetic reprogramming in sheep","authors":"C. U. Braz, M. Passamonti, Hasan Khatib","doi":"10.1093/eep/dvad010","DOIUrl":"https://doi.org/10.1093/eep/dvad010","url":null,"abstract":"\u0000 The mammalian genome undergoes two global epigenetic reprogramming events during the establishment of primordial germ cells and in the preimplantation embryo after fertilization. These events involve the erasure and reestablishment of DNA methylation marks. However, imprinted genes and transposable elements maintain their DNA methylation signatures to ensure normal embryonic development and genome stability. Despite extensive research in mice and humans, there is limited knowledge regarding environmentally induced epigenetic marks that escape epigenetic reprogramming in other species. Therefore, the objective of this study was to examine the characteristics and locations of genomic regions that evade epigenetic reprogramming in sheep, as well as to explore the biological functions of the genes within these regions. In a previous study, we identified 107 transgenerationally inherited differentially methylated cytosines (DMCs) in the F1 and F2 generations in response to a paternal methionine-supplemented diet. These DMCs were found in transposable elements, non-repetitive regions, imprinted and non-imprinted genes. Our findings suggest that genomic regions, rather than transposable elements and imprinted genes, have the propensity to escape reprogramming and serve as potential candidates for transgenerational epigenetic inheritance. Notably, 34 transgenerational methylated genes influenced by paternal nutrition escaped reprogramming, impacting growth, development, male fertility, cardiac disorders, and neurodevelopment. Intriguingly, among these genes, 21 have been associated with neural development and brain disorders, such as autism, schizophrenia, bipolar disease, and intellectual disability. This suggests a potential genetic overlap between brain and infertility disorders. Overall, our study supports the concept of transgenerational epigenetic inheritance of environmentally induced marks in mammals.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"28 17","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138955245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}