Pub Date : 2020-05-10eCollection Date: 2020-01-01DOI: 10.1093/eep/dvaa003
Michael R Hussey, Amber Burt, Maya A Deyssenroth, Brian P Jackson, Ke Hao, Shouneng Peng, Jia Chen, Carmen J Marsit, Todd M Everson
Heavy metal exposures, such as cadmium, can have negative effects on infant birth weight (BW)-among other developmental outcomes-with placental dysfunction potentially playing a role in these effects. In this study, we examined how differential placental expression of long non-coding RNAs (lncRNAs) may be associated with cadmium levels in placenta and whether differences in the expression of those lncRNAs were associated with fetal growth. In the Rhode Island Child Health Study, we used data from Illumina HiSeq whole transcriptome RNA sequencing (n = 199) to examine association between lncRNA expression and measures of infant BW as well as placental cadmium concentrations controlled for appropriate covariates. Of the 1191 lncRNAs sequenced, 46 demonstrated associations (q < 0.05) with BW in models controlling for infant sex, maternal age, BMI, maternal education, and smoking during pregnancy. Furthermore, four of these transcripts were associated with placental cadmium concentrations, with MIR22HG and ERVH48-1 demonstrating increases in expression associated with increasing cadmium exposure and elevated odds of small for gestational age birth, while AC114763.2 and LINC02595 demonstrated reduced expression associated with cadmium, but elevated odds of large for gestational age birth with increasing expression. We identified relationships between lncRNA expression with both placental cadmium concentrations and BW. This study provides evidence that disrupted placental expression of lncRNAs may be a part of cadmium's mechanisms of reproductive toxicity.
重金属(如镉)暴露会对婴儿出生体重(BW)及其他发育结果产生负面影响,而胎盘功能障碍可能在这些影响中起到一定作用。在这项研究中,我们研究了胎盘中长非编码 RNA(lncRNA)的不同表达可能与胎盘中的镉水平有何关联,以及这些 lncRNA 的表达差异是否与胎儿的生长有关。在罗德岛儿童健康研究(Rhode Island Child Health Study)中,我们利用Illumina HiSeq全转录组RNA测序数据(n = 199)研究了lncRNA表达与婴儿体重测量以及胎盘镉浓度之间的关系,并控制了适当的协变量。在测序的1191个lncRNA中,46个表现出相关性(q MIR22HG和ERVH48-1表现出与镉暴露增加相关的表达增加以及小胎龄出生几率升高,而AC114763.2和LINC02595表现出与镉相关的表达降低,但随着表达增加,大胎龄出生几率升高。我们确定了 lncRNA 表达与胎盘镉浓度和体重之间的关系。这项研究提供的证据表明,lncRNA的胎盘表达紊乱可能是镉的生殖毒性机制的一部分。
{"title":"Placental lncRNA expression associated with placental cadmium concentrations and birth weight.","authors":"Michael R Hussey, Amber Burt, Maya A Deyssenroth, Brian P Jackson, Ke Hao, Shouneng Peng, Jia Chen, Carmen J Marsit, Todd M Everson","doi":"10.1093/eep/dvaa003","DOIUrl":"10.1093/eep/dvaa003","url":null,"abstract":"<p><p>Heavy metal exposures, such as cadmium, can have negative effects on infant birth weight (BW)-among other developmental outcomes-with placental dysfunction potentially playing a role in these effects. In this study, we examined how differential placental expression of long non-coding RNAs (lncRNAs) may be associated with cadmium levels in placenta and whether differences in the expression of those lncRNAs were associated with fetal growth. In the Rhode Island Child Health Study, we used data from Illumina HiSeq whole transcriptome RNA sequencing (<i>n</i> = 199) to examine association between lncRNA expression and measures of infant BW as well as placental cadmium concentrations controlled for appropriate covariates. Of the 1191 lncRNAs sequenced, 46 demonstrated associations (<i>q</i> < 0.05) with BW in models controlling for infant sex, maternal age, BMI, maternal education, and smoking during pregnancy. Furthermore, four of these transcripts were associated with placental cadmium concentrations, with <i>MIR22HG</i> and <i>ERVH48-1</i> demonstrating increases in expression associated with increasing cadmium exposure and elevated odds of small for gestational age birth, while <i>AC114763.2</i> and <i>LINC02595</i> demonstrated reduced expression associated with cadmium, but elevated odds of large for gestational age birth with increasing expression. We identified relationships between lncRNA expression with both placental cadmium concentrations and BW. This study provides evidence that disrupted placental expression of lncRNAs may be a part of cadmium's mechanisms of reproductive toxicity.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/86/dvaa003.PMC7211362.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37939672","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}
Pub Date : 2020-05-06eCollection Date: 2020-01-01DOI: 10.1093/eep/dvaa004
Irina Lazar-Contes, Martin Roszkowski, Deepak K Tanwar, Isabelle M Mansuy
The concept of epigenetic inheritance proposes a new and unconventional way to think about heredity in health and disease, at the interface between genetics and the environment. Epigenetic inheritance is a form of biological inheritance not encoded in the DNA sequence itself but mediated by epigenetic factors. Because epigenetic factors can be modulated by the environment, they can relay this information to the genome and modify its activity consequentially. If epigenetic changes induced by environmental exposure are present in the germline and persist in germ cells during development until conception, they have the potential to transfer the traces of ancestral exposure to the progeny. This form of heredity relates to the extremely important question of nature versus nurture and how much of our own make-up is genetically or epigenetically determined, a question that remains largely unresolved. Because it questions the dominant dogma of genetics and brings a paradigm shift in sciences, it has to creating strong bridges between disciplines and provide solid causal evidence to be firmly established. The second edition of a conference fully dedicated to epigenetic inheritance was held in August 2019 in Zurich, Switzerland. This symposium titled 'Epigenetic inheritance: impact for biology and society' (http://www.epigenetic-inheritance-zurich.ethz.ch), gathered experts in the field of epigenetic inheritance to discuss the concept and pertinent findings, exchange views and expertise about models and methods, and address challenges raised by this new discipline. The symposium offered a mix of invited lectures and short talks selected from abstracts, poster sessions and a workshop 'Meet the experts: Q&A'. A tour of a local omics facility the Functional Genomics Center Zurich was also offered to interested participants. Additional comments and impressions were shared by attendees on Twitter #eisz19 during and after the symposium. This summary provides an overview of the different sessions and talks and describes the main findings presented.
{"title":"Symposium summary: Epigenetic inheritance-impact for biology and society 26-28 August 2019, Zurich, Switzerland.","authors":"Irina Lazar-Contes, Martin Roszkowski, Deepak K Tanwar, Isabelle M Mansuy","doi":"10.1093/eep/dvaa004","DOIUrl":"https://doi.org/10.1093/eep/dvaa004","url":null,"abstract":"<p><p>The concept of epigenetic inheritance proposes a new and unconventional way to think about heredity in health and disease, at the interface between genetics and the environment. Epigenetic inheritance is a form of biological inheritance not encoded in the DNA sequence itself but mediated by epigenetic factors. Because epigenetic factors can be modulated by the environment, they can relay this information to the genome and modify its activity consequentially. If epigenetic changes induced by environmental exposure are present in the germline and persist in germ cells during development until conception, they have the potential to transfer the traces of ancestral exposure to the progeny. This form of heredity relates to the extremely important question of nature versus nurture and how much of our own make-up is genetically or epigenetically determined, a question that remains largely unresolved. Because it questions the dominant dogma of genetics and brings a paradigm shift in sciences, it has to creating strong bridges between disciplines and provide solid causal evidence to be firmly established. The second edition of a conference fully dedicated to epigenetic inheritance was held in August 2019 in Zurich, Switzerland. This symposium titled 'Epigenetic inheritance: impact for biology and society' (http://www.epigenetic-inheritance-zurich.ethz.ch), gathered experts in the field of epigenetic inheritance to discuss the concept and pertinent findings, exchange views and expertise about models and methods, and address challenges raised by this new discipline. The symposium offered a mix of invited lectures and short talks selected from abstracts, poster sessions and a workshop 'Meet the experts: Q&A'. A tour of a local omics facility the Functional Genomics Center Zurich was also offered to interested participants. Additional comments and impressions were shared by attendees on Twitter #eisz19 during and after the symposium. This summary provides an overview of the different sessions and talks and describes the main findings presented.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37923588","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":"Erratum: Acetaminophen use during pregnancy and DNA methylation in the placenta of the extremely low gestational age newborn (ELGAN) cohort.","authors":"Kezia A Addo, Catherine Bulka, Radhika Dhingra, Hudson P Santos, Lisa Smeester, T Michael O'Shea, Rebecca C Fry","doi":"10.1093/eep/dvaa006","DOIUrl":"https://doi.org/10.1093/eep/dvaa006","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/eep/dvz010.][This corrects the article DOI: 10.1093/eep/dvz010.].</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37923589","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}
Pub Date : 2020-03-19eCollection Date: 2020-01-01DOI: 10.1093/eep/dvaa002
Rose Schrott, Susan K Murphy
The United States is swiftly moving toward increased legalization of medical and recreational cannabis. Currently considered the most commonly used illicit psychoactive drug, recreational cannabis is legal in 11 states and Washington, DC, and male use is an important and understudied concern. Questions remain, however, about the potential long-term consequences of this exposure and how cannabis might impact the epigenetic integrity of sperm in such a way that could influence the health and development of offspring. This review summarizes cannabis use and potency in the USA, provides a brief overview of DNA methylation as an epigenetic mechanism that is vulnerable in sperm to environmental exposures including cannabis, and summarizes studies that have examined the effects of parental exposure to cannabis or delta-9 tetrahydrocannabinol (THC, the main psychoactive component of cannabis) on the epigenetic profile of the gametes and behavior of offspring. These studies have demonstrated significant changes to the sperm DNA methylome following cannabis use in humans, and THC exposure in rats. Furthermore, the use of rodent models has shown methylation and behavioral changes in rats born to fathers exposed to THC or synthetic cannabinoids, or to parents who were both exposed to THC. These data substantiate an urgent need for additional studies assessing the effects of cannabis exposure on childhood health and development. This is especially true given the current growing state of cannabis use in the USA.
{"title":"Cannabis use and the sperm epigenome: a budding concern?","authors":"Rose Schrott, Susan K Murphy","doi":"10.1093/eep/dvaa002","DOIUrl":"https://doi.org/10.1093/eep/dvaa002","url":null,"abstract":"<p><p>The United States is swiftly moving toward increased legalization of medical and recreational cannabis. Currently considered the most commonly used illicit psychoactive drug, recreational cannabis is legal in 11 states and Washington, DC, and male use is an important and understudied concern. Questions remain, however, about the potential long-term consequences of this exposure and how cannabis might impact the epigenetic integrity of sperm in such a way that could influence the health and development of offspring. This review summarizes cannabis use and potency in the USA, provides a brief overview of DNA methylation as an epigenetic mechanism that is vulnerable in sperm to environmental exposures including cannabis, and summarizes studies that have examined the effects of parental exposure to cannabis or delta-9 tetrahydrocannabinol (THC, the main psychoactive component of cannabis) on the epigenetic profile of the gametes and behavior of offspring. These studies have demonstrated significant changes to the sperm DNA methylome following cannabis use in humans, and THC exposure in rats. Furthermore, the use of rodent models has shown methylation and behavioral changes in rats born to fathers exposed to THC or synthetic cannabinoids, or to parents who were both exposed to THC. These data substantiate an urgent need for additional studies assessing the effects of cannabis exposure on childhood health and development. This is especially true given the current growing state of cannabis use in the USA.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37771313","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}
Pub Date : 2020-02-04eCollection Date: 2020-01-01DOI: 10.1093/eep/dvz027
G T Mørkve Knudsen, F I Rezwan, A Johannessen, S M Skulstad, R J Bertelsen, F G Real, S Krauss-Etschmann, V Patil, D Jarvis, S H Arshad, J W Holloway, C Svanes
[This corrects the article DOI: 10.1093/eep/dvz023.][This corrects the article DOI: 10.1093/eep/dvz023.].
{"title":"Erratum: Epigenome-wide association of father's smoking with offspring DNA methylation: a hypothesis-generating study.","authors":"G T Mørkve Knudsen, F I Rezwan, A Johannessen, S M Skulstad, R J Bertelsen, F G Real, S Krauss-Etschmann, V Patil, D Jarvis, S H Arshad, J W Holloway, C Svanes","doi":"10.1093/eep/dvz027","DOIUrl":"https://doi.org/10.1093/eep/dvz027","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/eep/dvz023.][This corrects the article DOI: 10.1093/eep/dvz023.].</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37630403","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}
Pub Date : 2020-02-04eCollection Date: 2020-01-01DOI: 10.1093/eep/dvaa001
Margaret J Morris, Luke B Hesson, Neil A Youngson
Mitochondrial DNA (mtDNA) is a circular genome of 16 kb that is present in multiple copies in mitochondria. mtDNA codes for genes that contribute to mitochondrial structure and function. A long-standing question has asked whether mtDNA is epigenetically regulated similarly to the nuclear genome. Recently published data suggest that unlike the nuclear genome where CpG methylation is the norm, mtDNA is methylated predominantly at non-CpG cytosines. This raises important methodological considerations for future investigations. In particular, existing bisulphite PCR techniques may be unsuitable due to primers being biased towards amplification from unmethylated mtDNA. Here, we describe how this may have led to previous studies underestimating the level of mtDNA methylation and reiterate methodological strategies for its accurate assessment.
{"title":"Non-CpG methylation biases bisulphite PCR towards low or unmethylated mitochondrial DNA: recommendations for the field.","authors":"Margaret J Morris, Luke B Hesson, Neil A Youngson","doi":"10.1093/eep/dvaa001","DOIUrl":"https://doi.org/10.1093/eep/dvaa001","url":null,"abstract":"<p><p>Mitochondrial DNA (mtDNA) is a circular genome of 16 kb that is present in multiple copies in mitochondria. mtDNA codes for genes that contribute to mitochondrial structure and function. A long-standing question has asked whether mtDNA is epigenetically regulated similarly to the nuclear genome. Recently published data suggest that unlike the nuclear genome where CpG methylation is the norm, mtDNA is methylated predominantly at non-CpG cytosines. This raises important methodological considerations for future investigations. In particular, existing bisulphite PCR techniques may be unsuitable due to primers being biased towards amplification from unmethylated mtDNA. Here, we describe how this may have led to previous studies underestimating the level of mtDNA methylation and reiterate methodological strategies for its accurate assessment.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37722613","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}
Pub Date : 2020-01-30eCollection Date: 2020-01-01DOI: 10.1093/eep/dvz026
Christelle Leung, Bernard Angers, Patrick Bergeron
Physiological changes in anticipation of cyclic environmental events are common for the persistence of populations in fluctuating environments (e.g. seasons). However, dealing with sporadic resources such as the intermittent production of seed masting trees may be challenging unless reliable cues also make them predictable. To be adaptive, the anticipation of such episodic events would have to trigger the corresponding physiological response. Epigenetic modifications could result in such physiological anticipatory responses to future changes. The eastern chipmunk (Tamias striatus) is known to adjust its reproductive activity to match juvenile weaning with peak seed availability of masting trees, which are essential for their survival. We therefore expected that epigenetic changes would be linked to spring reproductive initiation in anticipation for beech seed availability in fall. We correlated the variation of DNA methylation profiles of 114 adult chipmunks captured in May with beech seeds abundance in September, over 4 years, for three distinct populations, as well as individuals sampled twice during reproductive and non-reproductive years. The significant correlation between spring epigenetic variation and the amount of food in the fall confirmed the phenotypic flexibility of individuals according to environmental fluctuations. Altogether, these results underlined the key role of epigenetic processes in anticipatory responses enabling organisms to persist in fluctuating environments.
{"title":"Epigenetic anticipation for food and reproduction.","authors":"Christelle Leung, Bernard Angers, Patrick Bergeron","doi":"10.1093/eep/dvz026","DOIUrl":"10.1093/eep/dvz026","url":null,"abstract":"<p><p>Physiological changes in anticipation of cyclic environmental events are common for the persistence of populations in fluctuating environments (e.g. seasons). However, dealing with sporadic resources such as the intermittent production of seed masting trees may be challenging unless reliable cues also make them predictable. To be adaptive, the anticipation of such episodic events would have to trigger the corresponding physiological response. Epigenetic modifications could result in such physiological anticipatory responses to future changes. The eastern chipmunk (<i>Tamias striatus</i>) is known to adjust its reproductive activity to match juvenile weaning with peak seed availability of masting trees, which are essential for their survival. We therefore expected that epigenetic changes would be linked to spring reproductive initiation in anticipation for beech seed availability in fall. We correlated the variation of DNA methylation profiles of 114 adult chipmunks captured in May with beech seeds abundance in September, over 4 years, for three distinct populations, as well as individuals sampled twice during reproductive and non-reproductive years. The significant correlation between spring epigenetic variation and the amount of food in the fall confirmed the phenotypic flexibility of individuals according to environmental fluctuations. Altogether, these results underlined the key role of epigenetic processes in anticipatory responses enabling organisms to persist in fluctuating environments.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37607428","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}
Pub Date : 2019-12-23eCollection Date: 2019-10-01DOI: 10.1093/eep/dvz025
Michael K Skinner
A conference summary of the fourth 2018 biannual Kenya Africa Conference 'Environment, Epigenetics and Reproduction' is provided. A special Environmental Epigenetics issue containing a number of papers in Volume 5, Issue 3 and 4 are discussed.
{"title":"2019 environment, epigenetics and reproduction.","authors":"Michael K Skinner","doi":"10.1093/eep/dvz025","DOIUrl":"https://doi.org/10.1093/eep/dvz025","url":null,"abstract":"<p><p>A conference summary of the fourth 2018 biannual Kenya Africa Conference 'Environment, Epigenetics and Reproduction' is provided. A special Environmental Epigenetics issue containing a number of papers in Volume 5, Issue 3 and 4 are discussed.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2019-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37498049","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}
Pub Date : 2019-12-14eCollection Date: 2019-10-01DOI: 10.1093/eep/dvz024
P M Herst, M Dalvai, M Lessard, P L Charest, P Navarro, C Joly-Beauparlant, A Droit, J M Trasler, S Kimmins, A J MacFarlane, M-O Benoit-Biancamano, J L Bailey
Persistent organic pollutants (POPs) can induce epigenetic changes in the paternal germline. Here, we report that folic acid (FA) supplementation mitigates sperm miRNA profiles transgenerationally following in utero paternal exposure to POPs in a rat model. Pregnant founder dams were exposed to an environmentally relevant POPs mixture (or corn oil) ± FA supplementation and subsequent F1-F4 male descendants were not exposed to POPs and were fed the FA control diet. Sperm miRNA profiles of intergenerational (F1, F2) and transgenerational (F3, F4) lineages were investigated using miRNA deep sequencing. Across the F1-F4 generations, sperm miRNA profiles were less perturbed with POPs+FA compared to sperm from descendants of dams treated with POPs alone. POPs exposure consistently led to alteration of three sperm miRNAs across two generations, and similarly one sperm miRNA due to POPs+FA; which was in common with one POPs intergenerationally altered sperm miRNA. The sperm miRNAs that were affected by POPs alone are known to target genes involved in mammary gland and embryonic organ development in F1, sex differentiation and reproductive system development in F2 and cognition and brain development in F3. When the POPs treatment was combined with FA supplementation, however, these same miRNA-targeted gene pathways were perturbed to a lesser extend and only in F1 sperm. These findings suggest that FA partially mitigates the effect of POPs on paternally derived miRNA in a intergenerational manner.
{"title":"Folic acid supplementation reduces multigenerational sperm miRNA perturbation induced by <i>in utero</i> environmental contaminant exposure.","authors":"P M Herst, M Dalvai, M Lessard, P L Charest, P Navarro, C Joly-Beauparlant, A Droit, J M Trasler, S Kimmins, A J MacFarlane, M-O Benoit-Biancamano, J L Bailey","doi":"10.1093/eep/dvz024","DOIUrl":"https://doi.org/10.1093/eep/dvz024","url":null,"abstract":"<p><p>Persistent organic pollutants (POPs) can induce epigenetic changes in the paternal germline. Here, we report that folic acid (FA) supplementation mitigates sperm miRNA profiles transgenerationally following <i>in utero</i> paternal exposure to POPs in a rat model. Pregnant founder dams were exposed to an environmentally relevant POPs mixture (or corn oil) ± FA supplementation and subsequent F1-F4 male descendants were not exposed to POPs and were fed the FA control diet. Sperm miRNA profiles of intergenerational (F1, F2) and transgenerational (F3, F4) lineages were investigated using miRNA deep sequencing. Across the F1-F4 generations, sperm miRNA profiles were less perturbed with POPs+FA compared to sperm from descendants of dams treated with POPs alone. POPs exposure consistently led to alteration of three sperm miRNAs across two generations, and similarly one sperm miRNA due to POPs+FA; which was in common with one POPs intergenerationally altered sperm miRNA. The sperm miRNAs that were affected by POPs alone are known to target genes involved in mammary gland and embryonic organ development in F1, sex differentiation and reproductive system development in F2 and cognition and brain development in F3. When the POPs treatment was combined with FA supplementation, however, these same miRNA-targeted gene pathways were perturbed to a lesser extend and only in F1 sperm. These findings suggest that FA partially mitigates the effect of POPs on paternally derived miRNA in a intergenerational manner.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2019-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvz024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37471496","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}