45
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Deleterious effects of endocrine disruptors are corrected in the mammalian germline by epigenome reprogramming

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Exposure to environmental endocrine-disrupting chemicals during pregnancy reportedly causes transgenerationally inherited reproductive defects. We hypothesized that to affect the grandchild, endocrine-disrupting chemicals must alter the epigenome of the germ cells of the in utero-exposed G1 male fetus. Additionally, to affect the great-grandchild, the aberration must persist in the germ cells of the unexposed G2 grandchild.

          Results

          Here, we treat gestating female mice with vinclozolin, bisphenol A, or di-(2-ethylhexyl)phthalate during the time when global de novo DNA methylation and imprint establishment occurs in the germ cells of the G1 male fetus. We map genome-wide features in purified G1 and G2 prospermatogonia, in order to detect immediate and persistent epigenetic aberrations, respectively. We detect changes in transcription and methylation in the G1 germline immediately after endocrine-disrupting chemicals exposure, but changes do not persist into the G2 germline. Additional analysis of genomic imprints shows no persistent aberrations in DNA methylation at the differentially methylated regions of imprinted genes between the G1 and G2 prospermatogonia, or in the allele-specific transcription of imprinted genes between the G2 and G3 soma.

          Conclusions

          Our results suggest that endocrine-disrupting chemicals exert direct epigenetic effects in exposed fetal germ cells, which are corrected by reprogramming events in the next generation. Avoiding transgenerational inheritance of environmentally-caused epigenetic aberrations may have played an evolutionary role in the development of dual waves of global epigenome reprogramming in mammals.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13059-015-0619-z) contains supplementary material, which is available to authorized users.

          Related collections

          Most cited references51

          • Record: found
          • Abstract: found
          • Article: not found

          Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004

          Background Bisphenol A (BPA) and 4-tertiary-octylphenol (tOP) are industrial chemicals used in the manufacture of polycarbonate plastics and epoxy resins (BPA) and nonionic surfactants (tOP). These products are in widespread use in the United States. Objectives We aimed to assess exposure to BPA and tOP in the U.S. general population. Methods We measured the total (free plus conjugated) urinary concentrations of BPA and tOP in 2,517 participants ≥ 6 years of age in the 2003–2004 National Health and Nutrition Examination Survey using automated solid-phase extraction coupled to isotope dilution–high-performance liquid chromatography–tandem mass spectrometry. Results BPA and tOP were detected in 92.6% and 57.4% of the persons, respectively. Least square geometric mean (LSGM) concentrations of BPA were significantly lower in Mexican Americans than in non-Hispanic blacks (p = 0.006) and non-Hispanic whites (p = 0.007); LSGM concentrations for non-Hispanic blacks and non-Hispanic whites were not statistically different (p = 0.21). Females had statistically higher BPA LSGM concentrations than males (p = 0.043). Children had higher concentrations than adolescents (p $45,000/year). Conclusions Urine concentrations of total BPA differed by race/ethnicity, age, sex, and household income. These first U.S. population representative concentration data for urinary BPA and tOP should help guide public health research priorities, including studies of exposure pathways, potential health effects, and risk assessment.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Plastics Derived Endocrine Disruptors (BPA, DEHP and DBP) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations

            Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1–F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the “plastics” or “lower dose plastics” mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Epigenetic reprogramming in mouse primordial germ cells.

              Genome-wide epigenetic reprogramming in mammalian germ cells, zygote and early embryos, plays a crucial role in regulating genome functions at critical stages of development. We show here that mouse primordial germ cells (PGCs) exhibit dynamic changes in epigenetic modifications between days 10.5 and 12.5 post coitum (dpc). First, contrary to previous suggestions, we show that PGCs do indeed acquire genome-wide de novo methylation during early development and migration into the genital ridge. However, following their entry into the genital ridge, there is rapid erasure of DNA methylation of regions within imprinted and non-imprinted loci. For most genes, the erasure commences simultaneously in PGCs in both male and female embryos, which is completed within 1 day of development. Based on the kinetics of this process, we suggest that this is an active demethylation process initiated upon the entry of PGCs into the gonadal anlagen. The timing of reprogramming in PGCs is crucial since it ensures that germ cells of both sexes acquire an equivalent epigenetic state prior to the differentiation of the definitive male and female germ cells in which new parental imprints are established subsequently. Some repetitive elements, however, show incomplete erasure, which may be essential for chromosome stability and for preventing activation of transposons to reduce the risk of germline mutations. Aberrant epigenetic reprogramming in the germ line would cause the inheritance of epimutations that may have consequences for human diseases as suggested by studies on mouse models. Copyright 2002 Elsevier Science Ireland Ltd.
                Bookmark

                Author and article information

                Contributors
                khurshed78@yahoo.com
                dtran27@gmail.com
                arthurli@coh.org
                xwu@coh.org
                cdwarden@umich.edu
                angelabai@ymail.com
                psingh@peds.uab.edu
                gerd.pfeifer@vai.org
                piroska.szabo@vai.org
                Journal
                Genome Biol
                Genome Biology
                BioMed Central (London )
                1465-6906
                1465-6914
                27 March 2015
                27 March 2015
                2015
                : 16
                : 1
                : 59
                Affiliations
                [ ]Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, Duarte, California 91010 USA
                [ ]Irell and Manella Graduate School of Biological Sciences, City of Hope, Duarte, California 91010 USA
                [ ]Department of Information Science, Beckman Research Institute, City of Hope, Duarte, California 91010 USA
                [ ]Eugene and Ruth Roberts Summer Academy, City of Hope, Duarte, California 91010 USA
                [ ]Department of Cancer Biology, Beckman Research Institute, City of Hope, Duarte, California 91010 USA
                [ ]Center for Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan 49503 USA
                Article
                619
                10.1186/s13059-015-0619-z
                4376074
                25853433
                ac3138b7-4fce-4038-b772-ce5c0cc562c6
                © Iqbal et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 December 2014
                : 23 February 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Genetics
                endocrine disruptor,germline epigenetic reprogramming,dna methylation,vinclozolin,bisphenol a,dehp,transgenerational epigenetic inheritance,fetal germ cell,genomic imprinting

                Comments

                Comment on this article