Environmental Epigenetics最新文献

{"title":"Serum lead, mercury, manganese, and copper and DNA methylation age among adults in Detroit, Michigan.","authors":"Evans K Lodge,&nbsp;Radhika Dhingra,&nbsp;Chantel L Martin,&nbsp;Rebecca C Fry,&nbsp;Alexandra J White,&nbsp;Cavin K Ward-Caviness,&nbsp;Agaz H Wani,&nbsp;Monica Uddin,&nbsp;Derek E Wildman,&nbsp;Sandro Galea,&nbsp;Allison E Aiello","doi":"10.1093/eep/dvac018","DOIUrl":"https://doi.org/10.1093/eep/dvac018","url":null,"abstract":"<p><p>Although the effects of lead, mercury, manganese, and copper on individual disease processes are well understood, estimating the health effects of long-term exposure to these metals at the low concentrations often observed in the general population is difficult. In addition, the health effects of joint exposure to multiple metals are difficult to estimate. Biological aging refers to the integrative progression of multiple physiologic and molecular changes that make individuals more at risk of disease. Biomarkers of biological aging may be useful to estimate the population-level effects of metal exposure prior to the development of disease in the population. We used data from 290 participants in the Detroit Neighborhood Health Study to estimate the effect of serum lead, mercury, manganese, and copper on three DNA methylation-based biomarkers of biological aging (Horvath Age, PhenoAge, and GrimAge). We used mixed models and Bayesian kernel machine regression and controlled for participant sex, race, ethnicity, cigarette use, income, educational attainment, and block group poverty. We observed consistently positive estimates of the effects between lead and GrimAge acceleration and mercury and PhenoAge acceleration. In contrast, we observed consistently negative associations between manganese and PhenoAge acceleration and mercury and Horvath Age acceleration. We also observed curvilinear relationships between copper and both PhenoAge and GrimAge acceleration. Increasing total exposure to the observed mixture of metals was associated with increased PhenoAge and GrimAge acceleration and decreased Horvath Age acceleration. These findings indicate that an increase in serum lead or mercury from the 25th to 75th percentile is associated with a ∼0.25-year increase in two epigenetic markers of all-cause mortality in a population of adults in Detroit, Michigan. While few of the findings were statistically significant, their consistency and novelty warrant interest.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"8 1","pages":"dvac018"},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9620967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10751606","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":"Combined exposure to polychlorinated biphenyls and high-fat diet modifies the global epitranscriptomic landscape in mouse liver.","authors":"Carolyn M Klinge, Kellianne M Piell, Belinda J Petri, Liqing He, Xiang Zhang, Jianmin Pan, Shesh N Rai, Kalina Andreeva, Eric C Rouchka, Banrida Wahlang, Juliane I Beier, Matthew C Cave","doi":"10.1093/eep/dvab008","DOIUrl":"10.1093/eep/dvab008","url":null,"abstract":"<p><p>Exposure to a single dose of polychlorinated biphenyls (PCBs) and a 12-week high-fat diet (HFD) results in nonalcoholic steatohepatitis (NASH) in mice by altering intracellular signaling and inhibiting epidermal growth factor receptor signaling. Post-transcriptional chemical modification (PTM) of RNA regulates biological processes, but the contribution of epitranscriptomics to PCB-induced steatosis remains unknown. This study tested the hypothesis that PCB and HFD exposure alters the global RNA epitranscriptome in male mouse liver. C57BL/6J male mice were fed a HFD for 12 weeks and exposed to a single dose of Aroclor 1260 (20 mg/kg), PCB 126 (20 µg/kg), both Aroclor 1260 and PCB 126 or vehicle control after 2 weeks on HFD. Chemical RNA modifications were identified at the nucleoside level by liquid chromatography-mass spectrometry. From 22 PTM global RNA modifications, we identified 10 significant changes in RNA modifications in liver with HFD and PCB 126 exposure. Only two modifications were significantly different from HFD control liver in all three PCB exposure groups: 2'-O-methyladenosine (Am) and N(6)-methyladenosine (m6A). Exposure to HFD + PCB 126 + Aroclor 1260 increased the abundance of N(6), O(2)-dimethyladenosine (m6Am), which is associated with the largest number of transcript changes. Increased m6Am and pseudouridine were associated with increased protein expression of the writers of these modifications: Phosphorylated CTD Interacting Factor 1 (PCIF1) and Pseudouridine Synthase 10 (PUS10), respectively, in HFD + PCB 126- + Aroclor 1260-exposed mouse liver. Increased N1-methyladenosine (m1A) and m6A were associated with increased transcript levels of the readers of these modifications: YTH N6-Methyladenosine RNA Binding Protein 2 (YTHDF2), YTH Domain Containing 2 (YTHDC2), and reader FMRP Translational Regulator 1 (FMR1) transcript and protein abundance. The results demonstrate that PCB exposure alters the global epitranscriptome in a mouse model of NASH; however, the mechanism for these changes requires further investigation.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"7 1","pages":"dvab008"},"PeriodicalIF":3.8,"publicationDate":"2021-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9731720","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 at birth potentially mediates the association between prenatal lead (Pb) exposure and infant neurodevelopmental outcomes.","authors":"Christine A Rygiel, Dana C Dolinoy, Kelly M Bakulski, Max T Aung, Wei Perng, Tamara R Jones, Maritsa Solano-González, Howard Hu, Martha M Tellez-Rojo, Lourdes Schnaas, Erika Marcela, Karen E Peterson, Jaclyn M Goodrich","doi":"10.1093/eep/dvab005","DOIUrl":"10.1093/eep/dvab005","url":null,"abstract":"<p><p>Early-life lead (Pb) exposure has been linked to adverse neurodevelopmental outcomes. Recent evidence has indicated a critical role of DNA methylation (DNAm) in cognition, and Pb exposure has also been shown to alter DNAm. However, it is unknown whether DNAm is part of the mechanism of Pb neurotoxicity. This longitudinal study investigated the associations between trimester-specific (T1, T2, and T3) maternal blood Pb concentrations, gene-specific DNAm in umbilical cord blood, and infant neurodevelopmental outcomes at 12 and 24 months of age (mental development index, psychomotor development index, and behavioral rating scale of orientation/engagement and emotional regulation) among 85 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study. In the mediation analysis for this pilot study, <i>P</i> < 0.1 was considered significant. DNAm at a locus in <i>CCSER1</i> (probe ID cg02901723) mediated the association between T2 Pb on 24-month orientation/engagement [indirect effect estimate 4.44, 95% confidence interval (-0.09, 10.68), <i>P</i> = 0.06] and emotional regulation [3.62 (-0.05, 8.69), <i>P</i> = 0.05]. Cg18515027 (<i>GCNT1</i>) DNAm mediated the association of T1 Pb [-4.94 (-10.6, -0.77), <i>P</i> = 0.01] and T2 Pb [-3.52 (-8.09, -0.36), <i>P</i> = 0.02] with 24-month EMOCI, but there was a positive indirect effect estimate between T2 Pb and 24-month psychomotor development index [1.25 (-0.11, 3.32), <i>P</i> = 0.09]. The indirect effect was significant for cg19703494 (<i>TRAPPC6A</i>) DNAm in the association between T2 Pb and 24-month mental development index [1.54 (0, 3.87), <i>P</i> = 0.05]. There was also an indirect effect of cg23280166 (<i>VPS11</i>) DNAm on T3 Pb and 24-month EMOCI [2.43 (-0.16, 6.38), <i>P</i> = 0.08]. These associations provide preliminary evidence for gene-specific DNAm as mediators between prenatal Pb and adverse cognitive outcomes in offspring.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"7 1","pages":"dvab005"},"PeriodicalIF":4.8,"publicationDate":"2021-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/35/dvab005.PMC8206046.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9177640","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":"Controlled human exposures to diesel exhaust: a human epigenome-wide experiment of target bronchial epithelial cells.","authors":"Andres Cardenas, Raj P Fadadu, Lars Van Der Laan, Cavin Ward-Caviness, Louis Granger, David Diaz-Sanchez, Robert B Devlin, Marie-Abèle Bind","doi":"10.1093/eep/dvab003","DOIUrl":"10.1093/eep/dvab003","url":null,"abstract":"<p><p>Diesel exhaust (DE) is a major contributor to ambient air pollution around the world. It is a known human carcinogen that targets the respiratory system and increases risk for many diseases, but there is limited research on the effects of DE exposure on the epigenome of human bronchial epithelial cells. Understanding the epigenetic impact of this environmental pollutant can elucidate biological mechanisms involved in the pathogenesis of harmful DE-related health effects. To estimate the causal effect of short-term DE exposure on the bronchial epithelial epigenome, we conducted a controlled single-blinded randomized crossover human experiment of exposure to DE and used bronchoscopy and Illumina 450K arrays for data collection and analysis, respectively. Of the 13 participants, 11 (85%) were male and 2 (15%) were female, and 12 (92%) were White and one (8%) was Hispanic; the mean age was 26 years (SD = 3.8 years). Eighty CpGs were differentially methylated, achieving the minimum possible exact <i>P</i>-value of <i>P </i>=<i> </i>2.44 × 10^-4 (<i>i.e.</i> 2/2¹³). In regional analyses, we found two differentially methylated regions (DMRs) annotated to the chromosome 5 open reading frame 63 genes (<i>C5orf63</i>; 7-CpGs) and unc-45 myosin chaperone A gene (<i>UNC45A</i>; 5-CpGs). Both DMRs showed increased DNA methylation after DE exposure. The average causal effects for the DMRs ranged from 1.5% to 6.0% increases in DNA methylation at individual CpGs. In conclusion, we found that short-term DE alters DNA methylation of genes in target bronchial epithelial cells, demonstrating epigenetic level effects of exposure that could be implicated in pulmonary pathologies.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"7 1","pages":"dvab003"},"PeriodicalIF":4.8,"publicationDate":"2021-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/54/dvab003.PMC8035831.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10294144","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":"Perinatal DEHP exposure induces sex- and tissue-specific DNA methylation changes in both juvenile and adult mice.","authors":"Siyu Liu,&nbsp;Kai Wang,&nbsp;Laurie K Svoboda,&nbsp;Christine A Rygiel,&nbsp;Kari Neier,&nbsp;Tamara R Jones,&nbsp;Raymond G Cavalcante,&nbsp;Justin A Colacino,&nbsp;Dana C Dolinoy,&nbsp;Maureen A Sartor","doi":"10.1093/eep/dvab004","DOIUrl":"https://doi.org/10.1093/eep/dvab004","url":null,"abstract":"<p><p>Di(2-ethylhexyl) phthalate (DEHP) is a type of phthalate plasticizer found in a variety of consumer products and poses a public health concern due to its metabolic and endocrine disruption activities. Dysregulation of epigenetic modifications, including DNA methylation, has been shown to be an important mechanism for the pathogenic effects of prenatal exposures, including phthalates. In this study, we used an established mouse model to study the effect of perinatal DEHP exposure on the DNA methylation profile in liver (a primary target tissue of DEHP) and blood (a common surrogate tissue) of both juvenile and adult mice. Despite exposure ceasing at 3 weeks of age (PND21), we identified thousands of sex-specific differential DNA methylation events in 5-month old mice, more than identified at PND21, both in blood and liver. Only a small number of these differentially methylated cytosines (DMCs) overlapped between the time points, or between tissues (i.e. liver and blood), indicating blood may not be an appropriate surrogate tissue to estimate the effects of DEHP exposure on liver DNA methylation. We detected sex-specific DMCs common between 3-week and 5-month samples, pointing to specific DNA methylation alterations that are consistent between weanling and adult mice. In summary, this is the first study to assess the genome-wide DNA methylation profiles in liver and blood at two different aged cohorts in response to perinatal DEHP exposure. Our findings cast light on the implications of using surrogate tissue instead of target tissue in human population-based studies and identify epigenetic biomarkers for DEHP exposure.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"7 1","pages":"dvab004"},"PeriodicalIF":3.8,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvab004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9544595","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":"Short- and long-term effects of perinatal phthalate exposures on metabolic pathways in the mouse liver.","authors":"Kari Neier, Luke Montrose, Kathleen Chen, Maureen A Malloy, Tamara R Jones, Laurie K Svoboda, Craig Harris, Peter X K Song, Subramaniam Pennathur, Maureen A Sartor, Dana C Dolinoy","doi":"10.1093/eep/dvaa017","DOIUrl":"10.1093/eep/dvaa017","url":null,"abstract":"<p><p>Phthalates have been demonstrated to interfere with metabolism, presumably by interacting with peroxisome proliferator-activated receptors (PPARs). However, mechanisms linking developmental phthalate exposures to long-term metabolic effects have not yet been elucidated. We investigated the hypothesis that developmental phthalate exposure has long-lasting impacts on PPAR target gene expression and DNA methylation to influence hepatic metabolic profiles across the life course. We utilized an established longitudinal mouse model of perinatal exposures to diethylhexyl phthalate and diisononyl phthalate, and a mixture of diethylhexyl phthalate+diisononyl phthalate. Exposure was through the diet and spanned from 2 weeks before mating until weaning at postnatal day 21 (PND21). Liver tissue was analyzed from the offspring of exposed and control mice at PND21 and in another cohort of exposed and control mice at 10 months of age. RNA-seq and pathway enrichment analyses indicated that acetyl-CoA metabolic processes were altered in diisononyl phthalate-exposed female livers at both PND21 and 10 months (FDR = 0.0018). Within the pathway, all 13 significant genes were potential PPAR target genes. Promoter DNA methylation was altered at three candidate genes, but persistent effects were only observed for <i>Fasn</i>. Targeted metabolomics indicated that phthalate-exposed females had decreased acetyl-CoA at PND21 and increased acetyl-CoA and acylcarnitines at 10 months. Together, our data suggested that perinatal phthalate exposures were associated with short- and long-term activation of PPAR target genes, which manifested as increased fatty acid production in early postnatal life and increased fatty acid oxidation in adulthood. This presents a novel molecular pathway linking developmental phthalate exposures and metabolic health outcomes.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"6 1","pages":"dvaa017"},"PeriodicalIF":3.8,"publicationDate":"2020-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38777160","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 environmental exposure to bisphenols and epigenome-wide DNA methylation in infant cord blood.","authors":"Carolyn F McCabe,&nbsp;Vasantha Padmanabhan,&nbsp;Dana C Dolinoy,&nbsp;Steven E Domino,&nbsp;Tamara R Jones,&nbsp;Kelly M Bakulski,&nbsp;Jaclyn M Goodrich","doi":"10.1093/eep/dvaa021","DOIUrl":"https://doi.org/10.1093/eep/dvaa021","url":null,"abstract":"<p><p>Maternal prenatal exposures, including bisphenol A (BPA), are associated with offspring's risk of disease later in life. Alterations in DNA methylation may be a mechanism through which altered prenatal conditions (e.g. maternal exposure to environmental toxicants) elicit this disease risk. In the Michigan Mother and Infant Pairs Cohort, maternal first-trimester urinary BPA, bisphenol F, and bisphenol S concentrations were tested for association with DNA methylation patterns in infant umbilical cord blood leukocytes (<i>N</i> = 69). We used the Illumina Infinium MethylationEPIC BeadChip to quantitatively evaluate DNA methylation across the epigenome; 822 020 probes passed pre-processing and quality checks. Single-site DNA methylation and bisphenol models were adjusted for infant sex, estimated cell-type proportions (determined using cell-type estimation algorithm), and batch as covariates. Thirty-eight CpG sites [false discovery rate (FDR) <0.05] were significantly associated with maternal BPA exposure. Increasing BPA concentrations were associated with lower DNA methylation at 87% of significant sites. BPA exposure associated DNA methylation sites were enriched for 38 pathways significant at FDR <0.05. The pathway or gene-set with the greatest odds of enrichment for differential methylation (FDR <0.05) was type I interferon receptor binding. This study provides a novel understanding of fetal response to maternal bisphenol exposure through epigenetic change.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"6 1","pages":"dvaa021"},"PeriodicalIF":3.8,"publicationDate":"2020-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38777164","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":"Epigenome-wide association study (EWAS) for potential transgenerational disease epigenetic biomarkers in sperm following ancestral exposure to the pesticide methoxychlor.","authors":"Eric E Nilsson,&nbsp;Jennifer L M Thorson,&nbsp;Millissia Ben Maamar,&nbsp;Daniel Beck,&nbsp;Michael K Skinner","doi":"10.1093/eep/dvaa020","DOIUrl":"https://doi.org/10.1093/eep/dvaa020","url":null,"abstract":"<p><p>Environmental exposures such as chemical toxicants can alter gene expression and disease susceptibility through epigenetic processes. Epigenetic changes can be passed to future generations through germ cells through epigenetic transgenerational inheritance of increased disease susceptibility. The current study used an epigenome-wide association study (EWAS) to investigate whether specific transgenerational epigenetic signatures of differential DNA methylation regions (DMRs) exist that are associated with particular disease states in the F3 generation great-grand offspring of F0 generation rats exposed during gestation to the agricultural pesticide methoxychlor. The transgenerational epigenetic profiles of sperm from F3 generation methoxychlor lineage rats that have only one disease state were compared to those that have no disease. Observations identify disease specific patterns of DMRs for these transgenerational rats that can potentially serve as epigenetic biomarkers for prostate disease, kidney disease, obesity, and the presence of multiple diseases. The chromosomal locations, genomic features, and gene associations of the DMRs are characterized. Disease specific DMR sets contained DMR-associated genes that have previously been shown to be associated with that specific disease. Future epigenetic biomarkers could potentially be developed and validated for humans as a disease susceptibility diagnostic tool to facilitate preventative medicine and management of disease.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"6 1","pages":"dvaa020"},"PeriodicalIF":3.8,"publicationDate":"2020-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/83/dvaa020.PMC7757123.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38777161","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 lead exposure and cord blood DNA methylation in PROGRESS: an epigenome-wide association study.","authors":"Jonathan A Heiss,&nbsp;Martha M Téllez-Rojo,&nbsp;Guadalupe Estrada-Gutiérrez,&nbsp;Lourdes Schnaas,&nbsp;Chitra Amarasiriwardena,&nbsp;Andrea A Baccarelli,&nbsp;Robert O Wright,&nbsp;Allan C Just","doi":"10.1093/eep/dvaa014","DOIUrl":"https://doi.org/10.1093/eep/dvaa014","url":null,"abstract":"<p><p>The effects of prenatal lead exposure on child development include impaired growth and cognitive function. DNA methylation might be involved in the underlying mechanisms and previous epigenome-wide association studies reported associations between lead exposure during pregnancy and cord blood methylation levels. However, it is unclear during which developmental stage lead exposure is most harmful. Cord blood methylation levels were assayed in 420 children from a Mexican pre-birth cohort using the Illumina Infinium MethylationEPIC microarray. Lead concentrations were measured in umbilical cord blood as well as in blood samples from the mothers collected at 2nd and 3rd trimester and delivery using inductively coupled plasma-mass spectrometry. In addition, maternal bone lead levels were measured in tibia and patella using X-ray fluorescence. Comprehensive quality control and preprocessing of microarray data was followed by an unbiased restriction to methylation sites with substantial variance. Methylation levels at 202 111 cytosine-phosphate-guanine sites were regressed on each exposure adjusting for child sex, leukocyte composition, batch variables, gestational age, birthweight-for-gestational-age, maternal age, maternal education and mode of delivery. We find no association between prenatal lead exposure and cord blood methylation. This null result is strengthened by a sensitivity analysis showing that in the same dataset known biomarkers for birthweight-for-gestational-age can be recovered and the fact that phenotypic associations with lead exposure have been described in the same cohort.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"6 1","pages":"dvaa014"},"PeriodicalIF":3.8,"publicationDate":"2020-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38716576","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":"Metabolic diseases affect male reproduction and induce signatures in gametes that may compromise the offspring health.","authors":"Sara C Pereira, Luís Crisóstomo, Mário Sousa, Pedro F Oliveira, Marco G Alves","doi":"10.1093/eep/dvaa019","DOIUrl":"10.1093/eep/dvaa019","url":null,"abstract":"<p><p>The most prevalent diseases worldwide are non-communicable such as obesity and type 2 diabetes. Noteworthy, the prevalence of obesity and type 2 diabetes is expected to steadily increase in the next decades, mostly fueled by bad feeding habits, stress, and sedentarism. The reproductive function of individuals is severely affected by abnormal metabolic environments, both at mechanical and biochemical levels. Along with mechanical dysfunctions, and decreased sperm quality (promoted both directly and indirectly by metabolic abnormalities), several studies have already reported the potentially harmful effects of metabolic disorders in the genetic and epigenetic cargo of spermatozoa, and the epigenetic inheritance of molecular signatures induced by metabolic profile (paternal diet, obesity, and diabetes). The inheritance of epigenetic factors towards the development of metabolic abnormalities means that more people in reproductive age can potentially suffer from these disorders and for longer periods. In its turn, these individuals can also transmit this (epi)genetic information to future generations, creating a vicious cycle. In this review, we collect the reported harmful effects related to acquired metabolic disorders and diet in sperm parameters and male reproductive potential. Besides, we will discuss the novel findings regarding paternal epigenetic inheritance, particularly the ones induced by paternal diet rich in fats, obesity, and type 2 diabetes. We analyze the data attained with <i>in vitro</i> and animal models as well as in long-term transgenerational population studies. Although the findings on this topic are very recent, epigenetic inheritance of metabolic disease has a huge societal impact, which may be crucial to tackle the 'fat epidemic' efficiently.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"6 1","pages":"dvaa019"},"PeriodicalIF":3.8,"publicationDate":"2020-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38716581","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}