Environmentally induced epigenetic toxicity: potential public health concerns

Critical Reviews in Toxicology

Volumn 46, Issue 8, 2016, Pages 676-700

  Marczylo, Emma L ^a   Jacobs, Miriam N ^a   Gant, Timothy W ^a  

^a Toxicology Department   (United Kingdom)

Author keywords

Adverse outcomes; DNA methylation; environmental exposures; epigenetic machinery; histone modification; human cohorts; non coding RNA; rodent models

Indexed keywords

DNA; UNTRANSLATED RNA; POLLUTANT;

CONCEPTION; DNA METHYLATION; ENVIRONMENTAL EXPOSURE; ENVIRONMENTAL FACTOR; EPIGENETICS; GAMETOGENESIS; GENETIC TOXICOLOGY; GENOTOXICITY; GERM CELL; HUMAN; LIFE CYCLE; MAMMAL; METABOLISM; NONHUMAN; PUBLIC HEALTH; REVIEW; SOMATIC CELL; ANIMAL; DRUG EFFECTS; GENETIC EPIGENESIS; POLLUTANT; RISK ASSESSMENT; TOXICITY;

ANIMALS; ENVIRONMENTAL EXPOSURE; ENVIRONMENTAL POLLUTANTS; EPIGENESIS, GENETIC; HUMANS; PUBLIC HEALTH; RISK ASSESSMENT;

EID: 84983042266     PISSN: 10408444     EISSN: 15476898     Source Type: Journal    
DOI: 10.1080/10408444.2016.1175417     Document Type: Review

References (207)

1. U.Aapola, K.Kawasaki, H.S.Scott, J.Ollila, M.Vihinen, M.Heino, A.Shintani, K.Kawasaki, S.Minoshima, K.Krohn,. 2000. Isolation and initial characterization of a novel zinc finger gene, DNMT3L, on 21q22.3, related to the cytosine-5-methyltransferase 3 gene family. Genomics. 65:293–298.
2. ALSPAC Peer-Reviewed Publications. Available from:http://www.bristol.ac.uk/alspac/researchers/research/papers/.
3. M.D.Anway, A.S.Cupp, M.Uzumcu, M.K.Skinner 2005. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 308:1466–1469.
4. A.Baccarelli, V.Bollati 2009. Epigenetics and environmental chemicals. Curr Opin Pediatr. 21:243–251.
5. K.M.Bakulski, M.D.Fallin 2014. Epigenetic epidemiology:promises for public health research. Environ Mol Mutagen. 55:171–183.
6. D.J.Barker 2007. The origins of the developmental origins theory. J Intern Med. 261:412–417.
7. M.S.Bartolomei, A.C.Ferguson-Smith 2011. Mammalian genomic imprinting. Cold Spring Harb Perspect Biol. 3:a002592.
8. S.C.Barton, M.A.Surani, M.L.Norris 1984. Role of paternal and maternal genomes in mouse development. Nature. 311:374–376.
9. L.Baselga-Escudero, A.Pascual-Serrano, A.Ribas-Latre, E.Casanova, M.J.Salvado, L.Arola, A.Arola-Arnal, C.Blade 2015. Long-term supplementation with a low dose of proanthocyanidins normalized liver miR-33a and miR-122 levels in high-fat diet-induced obese rats. Nutr Res (New York, NY). 35:337–345.
10. N.Beaujean 2014. Histone post-translational modifications in preimplantation mouse embryos and their role in nuclear architecture. Mol Reprod Dev. 81:100–112.
11. G.Begum, A.Davies, A.Stevens, M.Oliver, A.Jaquiery, J.Challis, J.Harding, F.Bloomfield, A.White 2013. Maternal undernutrition programs tissue-specific epigenetic changes in the glucocorticoid receptor in adult offspring. Endocrinology. 154:4560–4569.
12. T.H.Bestor, V.M.Ingram 1983. Two DNA methyltransferases from murine erythroleukemia cells:purification, sequence specificity, and mode of interaction with DNA. Proc Natl Acad Sci USA. 80:5559–5563.
13. S.R.Bhaumik, E.Smith, A.Shilatifard 2007. Covalent modifications of histones during development and disease pathogenesis. Nat Struct Mol Biol. 14:1008–1016.
14. D.M.Bielawski, F.M.Zaher, D.M.Svinarich, E.L.Abel 2002. Paternal alcohol exposure affects sperm cytosine methyltransferase messenger RNA levels. Alcohol Clin Exp Res. 26:347–351.
15. A.Bird, M.Taggart, M.Frommer, O.J.Miller, D.Macleod 1985. A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell. 40:91–99.
16. A.P.Bird 1980. DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res. 8:1499–1504.
17. A.P.Bird, M.H.Taggart 1980. Variable patterns of total DNA and rDNA methylation in animals. Nucleic Acids Res. 8:1485–1497.
18. A.Boyd, J.Golding, J.Macleod, D.A.Lawlor, A.Fraser, J.Henderson, L.Molloy, A.Ness, S.Ring, G.Davey Smith 2013. Cohort profile:the 'children of the 90s' – the index offspring of the Avon Longitudinal Study of Parents and Children. Int J Epidemiol. 42:111–127.
19. D.L.Buscariollo, X.Fang, V.Greenwood, H.Xue, S.A.Rivkees, C.C.Wendler 2014. Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice. PLoS One. 9:e87547.
20. N.Carey 2011. The epigenetics revolution:how modern biology is rewriting our understanding of genetics, disease and inheritance. London:Icon Books Ltd.
21. J.Carlin, R.George, T.M.Reyes 2013. Methyl donor supplementation blocks the adverse effects of maternal high fat diet on offspring physiology. PLoS One. 8:e63549. Epub 2013/05/10.
22. D.T.Carrell 2012. Epigenetics of the male gamete. Fertil Steril. 97:267–274.
23. H.H.Chao, X.F.Zhang, B.Chen, B.Pan, L.J.Zhang, L.Li, X.F.Sun, Q.H.Shi, W.Shen 2012. Bisphenol A exposure modifies methylation of imprinted genes in mouse oocytes via the estrogen receptor signaling pathway. Histochem Cell Biol. 137:249–259.
24. H.Chen, S.Li, J.Liu, B.A.Diwan, J.C.Barrett, M.P.Waalkes 2004. Chronic inorganic arsenic exposure induces hepatic global and individual gene hypomethylation:implications for arsenic hepatocarcinogenesis. Carcinogenesis. 25:1779–1786.
25. Y.Chervona, M.Costa 2012. The control of histone methylation and gene expression by oxidative stress, hypoxia, and metals. Free Radic Biol Med. 53:1041–1047.
26. Y.H.Chiou, S.H.Liou, R.H.Wong, C.Y.Chen, H.Lee 2015. Nickel may contribute to EGFR mutation and synergistically promotes tumor invasion in EGFR-mutated lung cancer via nickel-induced microRNA-21 expression. Toxicol Lett. 237:46–54.
27. S.W.Choi, F.Stickel, H.W.Baik, Y.I.Kim, H.K.Seitz, J.B.Mason 1999. Chronic alcohol consumption induces genomic but not p53-specific DNA hypomethylation in rat colon. J Nutr. 129:1945–1950.
28. M.S.Cook, R.Blelloch 2013. Small RNAs in germline development. Curr Top Dev Biol. 102:159–205.
29. C.R.Darwin 1859. On the origin of species by means of natural selection, or the preservation of favoured races in the struggle for life. 1st ed. London:John Murray.
30. C.R.Darwin 1868. The variation of animals and plants under domestication. 1st ed. London:John Murray.
31. W.Dean 2014. DNA methylation and demethylation:a pathway to gametogenesis and development. Mol Reprod Dev. 81:113–125.
32. A.M.Deaton, A.Bird 2011. CpG islands and the regulation of transcription. Genes Dev. 25:1010–1022.
33. D.C.Dolinoy 2008. The agouti mouse model:an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome. Nutr Rev. 66:S7–S11.
34. D.C.Dolinoy, D.Huang, R.L.Jirtle 2007. Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci USA. 104:13056–13061.
35. ECETOC. 2015. The role of epigenetics in reproductive toxicology. Available from:http://www.ecetoc.org/eventsmanager/62/258/The-Role-of-Epigenetics-in-Reproductive-Toxicity/.
36. ECETOC. 2016. Noncoding RNAs and risk assessment science.
37. EFSA. 2013. Scientific opinion on the hazard assessment of endocrine disruptors:scientific criteria for identification of endocrine disruptors and appropriateness of existing test methods for assessing effects mediated by these substances on human health and the environment. EFSA J. 11:3132–3216.
38. C.Faulk, A.Barks, D.C.Dolinoy 2013. Phylogenetic and DNA methylation analysis reveal novel regions of variable methylation in the mouse IAP class of transposons. BMC Genomics. 14:48.
39. T.P.FoleyJr, Z.Limanova, E.Potlukova 2015. Medical consequences of Chernobyl with focus on the endocrine system:Part 1. Casopis Lekaru Ceskych. 154:227–231.
40. R.Galupa, E.Heard 2015. X-chromosome inactivation:new insights into cis and trans regulation. Curr Opin Genet Dev. 31:57–66.
41. K.Gapp, A.Jawaid, P.Sarkies, J.Bohacek, P.Pelczar, J.Prados, L.Farinelli, E.Miska, I.M.Mansuy 2014. Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat Neurosci. 17:667–669.
42. J.Garcia-Lopez, L.Alonso, D.B.Cardenas, H.Artaza-Alvarez, D.Hourcade Jde, S.Martinez, M.A.Brieno-Enriquez, J.Del Mazo 2015. Diversity and functional convergence of small noncoding RNAs in male germ cell differentiation and fertilization. RNA. 21:946–962.
43. S.F.Gilbert 2014. Developmental biology. 10th ed. Sunderland, MA, USA:Sinauer Associates, Inc.
44. J.Golding 2010. Republished paper:determinants of child health and development:the contribution of ALSPAC – a personal view of the birth cohort study. Postgrad Med J. 86:387–390.
45. L.T.Gou, P.Dai, J.H.Yang, Y.Xue, Y.P.Hu, Y.Zhou, J.Y.Kang, X.Wang, H.Li, M.M.Hua,. 2014. Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis. Cell Res. 24:680–700.
46. B.Govindarajan, R.Klafter, M.S.Miller, C.Mansur, M.Mizesko, X.Bai, K.LaMontagneJr, J.L.Arbiser 2002. Reactive oxygen-induced carcinogenesis causes hypermethylation of p16(Ink4a) and activation of MAP kinase. Mol Med (Cambridge, Mass). 8:1–8.
47. H.Gowher, K.Liebert, A.Hermann, G.Xu, A.Jeltsch 2005. Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L. J Biol Chem. 280:13341–13348.
48. V.Grandjean, P.Gounon, N.Wagner, L.Martin, K.D.Wagner, F.Bernex, F.Cuzin, M.Rassoulzadegan 2009. The miR-124-Sox9 paramutation:RNA-mediated epigenetic control of embryonic and adult growth. Development. 136:3647–3655.
49. L.E.GrayJr, J.Furr 2008. Vinclozolin treatment induces reproductive malformations and infertility in male rats when administered during sexual but not gonadal differentiation; however, the effects are not transmitted to the subsequent generations. Biol Reprod. 78:227.
50. J.M.Greally, M.N.Jacobs 2013. In vitro and in vivo testing methods of epigenomic endpoints for evaluating endocrine disruptors. Altex. 30:445–471.
51. K.L.Greathouse, T.Bredfeldt, J.I.Everitt, K.Lin, T.Berry, K.Kannan, M.L.Mittelstadt, S.M.Ho, C.L.Walker 2012. Environmental estrogens differentially engage the histone methyltransferase EZH2 to increase risk of uterine tumorigenesis. Mol Cancer Res:MCR. 10:546–557.
52. P.Greaves 2000. Histopathology of preclinical toxicity studies:interpretation and relevance in drug safety evaluation. 2nd ed. New York:Elsevier Science.
53. P.Grote, B.G.Herrmann 2015. Long noncoding RNAs in organogenesis:making the difference. Trends Genet. 31:329–335.
54. J.A.Hackett, R.Sengupta, J.J.Zylicz, K.Murakami, C.Lee, T.A.Down, M.A.Surani 2013. Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine. Science. 339:448–452.
55. J.A.Hackett, M.A.Surani 2013. DNA methylation dynamics during the mammalian life cycle. Philos Trans R Soc Lond. B, Biol Sci. 368:20110328.
56. S.Halappanavar, J.Nikota, D.Wu, A.Williams, C.L.Yauk, M.Stampfli 2013. IL-1 receptor regulates microRNA-135b expression in a negative feedback mechanism during cigarette smoke-induced inflammation. J Immunol. 190:3679–3686.
57. B.J.Hale, C.X.Yang, J.W.Ross 2014. Small RNA regulation of reproductive function. Mol Reprod Dev. 81:148–159.
58. C.A.Hamm, F.F.Costa 2015. Epigenomes as therapeutic targets. Pharmacol Ther. 151:72–86.
59. Y.Hatanaka, K.Inoue, M.Oikawa, S.Kamimura, N.Ogonuki, E.N.Kodama, Y.Ohkawa, Y.Tsukada, A.Ogura 2015. Histone chaperone CAF-1 mediates repressive histone modifications to protect preimplantation mouse embryos from endogenous retrotransposons. Proc Natl Acad Sci USA. 112:14641–14646.
60. Z.Herceg, M.P.Lambert, K.van Veldhoven, C.Demetriou, P.Vineis, M.T.Smith, K.Straif, C.P.Wild 2013. Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation. Carcinogenesis. 34:1955–1967.
61. K.Hogg, P.S.Western 2015. Refurbishing the germline epigenome:out with the old, in with the new. Semin Cell Dev Biol. 45:104–113.
62. L.Hou, X.Zhang, D.Wang, A.Baccarelli 2012. Environmental chemical exposures and human epigenetics. Int J Epidemiol. 41:79–105.
63. L.A.Hughes, P.A.van den Brandt, A.P.de Bruine, K.A.Wouters, S.Hulsmans, A.Spiertz, R.A.Goldbohm, A.F.de Goeij, J.G.Herman, M.P.Weijenberg,. 2009. Early life exposure to famine and colorectal cancer risk:a role for epigenetic mechanisms. PLoS One. 4:e7951.
64. C.Ignacio, S.M.Mooney, F.A.Middleton 2014. Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichment. Front Pediatr. 2:00103. DOI:10.3389/fped.2014.00103.
65. K.Inawaka, M.Kawabe, S.Takahashi, Y.Doi, Y.Tomigahara, H.Tarui, J.Abe, S.Kawamura, T.Shirai. 2009. Maternal exposure to anti-androgenic compounds, vinclozolin, flutamide and procymidone, has no effects on spermatogenesis and DNA methylation in male rats of subsequent generations. Toxicol Appl Pharmacol. 237:178–187.
66. J.R.M.Innes, F.M.Garner, J.L.Stokey 1967. Respiratory disease in rats. In:Cotchin E, Roe FJC, editors. Pathology of laboratory rats and mice. 2nd ed. Oxford and Edinburgh:Blackwell Scientific. p. 229–257.
67. J.P.Issa, S.B.Baylin, S.A.Belinsky 1996. Methylation of the estrogen receptor CpG island in lung tumors is related to the specific type of carcinogen exposure. Cancer Res. 56:3655–3658.
68. S.Ito, L.Shen, Q.Dai, S.C.Wu, L.B.Collins, J.A.Swenberg, C.He, Y.Zhang 2011. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 333:1300–1303.
69. K.N.Ivey, D.Srivastava 2015. microRNAs as developmental regulators. Cold Spring Harb Perspect Biol. 7:a008144.
70. A.Izzotti, R.Balansky, F.D'Agostini, M.Longobardi, C.Cartiglia, R.T.Micale, S.La Maestra, A.Camoirano, G.Ganchev, M.Iltcheva,. 2014. Modulation by metformin of molecular and histopathological alterations in the lung of cigarette smoke-exposed mice. Cancer Med. 3:719–730.
71. M.Jacobs, K.Louekari, A.Colacci, M.Luijten, B.Hakkert, M.Paparella, P.Vasseur 2015. The international regulatory need for tests and information to develop an Integrated Approach to Testing and Assessment (IATA) of non-genotoxic carcinogens. Toxicol Lett. 238:S123.
72. T.Jenuwein, C.D.Allis 2001. Translating the histone code. Science. 293:1074–1080.
73. Y.Jiang, W.Xia, J.Yang, Y.Zhu, H.Chang, J.Liu, W.Huo, B.Xu, X.Chen, Y.Li,. 2015. BPA-induced DNA hypermethylation of the master mitochondrial genePGC-1α contributes to cardiomyopathy in male rats. Toxicology. 329:21–31.
74. H.Jin, J.X.Chen, H.Wang, G.Lu, A.Liu, G.Li, S.Tu, Y.Lin, C.S.Yang 2015. NNK-induced DNA methyltransferase 1 in lung tumorigenesis in A/J mice and inhibitory effects of (-)-epigallocatechin-3-gallate. Nutr Cancer. 67:167–176.
75. E.R.Kabir, M.S.Rahman, I.Rahman 2015. A review on endocrine disruptors and their possible impacts on human health. Environ Toxicol Pharmacol. 40:241–258.
76. K.Kamiya, K.Ozasa, S.Akiba, O.Niwa, K.Kodama, N.Takamura, E.K.Zaharieva, Y.Kimura, R.Wakeford 2015. Long-term effects of radiation exposure on health. Lancet (London, England). 386:469–478.
77. J.H.Kamstra, P.Alestrom, J.M.Kooter, J.Legler 2015. Zebrafish as a model to study the role of DNA methylation in environmental toxicology. Environ Sci Pollut Res. 22:16262–16276.
78. C.Kanduri 2016. Long noncoding RNAs:lessons from genomic imprinting. Biochim Biophys Acta. 1859:102–111.
79. F.Kassie, S.Kalscheuer, I.Matise, L.Ma, T.Melkamu, P.Upadhyaya, S.S.Hecht 2010. Inhibition of vinyl carbamate-induced pulmonary adenocarcinoma by indole-3-carbinol and myo-inositol in A/J mice. Carcinogenesis. 31:239–245.
80. S.P.Khare, F.Habib, R.Sharma, N.Gadewal, S.Gupta, S.Galande 2012. HIstome-a relational knowledgebase of human histone proteins and histone modifying enzymes. Nucleic Acids Res. 40:D337–D342.
81. J.Kiani, V.Grandjean, R.Liebers, F.Tuorto, H.Ghanbarian, F.Lyko, F.Cuzin, M.Rassoulzadegan 2013. RNA-mediated epigenetic heredity requires the cytosine methyltransferase Dnmt2. PLoS Genet. 9:e1003498.
82. K.R.Kilcoyne, L.B.Smith, N.Atanassova, S.Macpherson, C.McKinnell, S.van den Driesche, M.S.Jobling, T.J.Chambers, K.De Gendt, G.Verhoeven,. 2014. Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells. Proc Natl Acad Sci USA. 111:E1924–E1932.
83. R.D.Kornberg, Y.Lorch 1999. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell. 98:285–294.
84. T.Kouzarides 2007. Chromatin modifications and their function. Cell. 128:693–705.
85. D.G.Kristensen, N.E.Skakkebaek, E.Rajpert-De Meyts, K.Almstrup 2013. Epigenetic features of testicular germ cell tumours in relation to epigenetic characteristics of foetal germ cells. Int J Dev Biol. 57:309–317.
86. M.Kundakovic, K.Gudsnuk, J.B.Herbstman, D.Tang, F.P.Perera, F.A.Champagne 2015. DNA methylation of BDNF as a biomarker of early-life adversity. Proc Natl Acad Sci USA. 112:6807–6813.
87. S.Kuramochi-Miyagawa, T.Watanabe, K.Gotoh, Y.Totoki, A.Toyoda, M.Ikawa, N.Asada, K.Kojima, Y.Yamaguchi, T.W.Ijiri,. 2008. DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev. 22:908–917.
88. D.J.Laird 2013. Humans put their eggs in more than one basket. Nat Cell Biol. 15:13–15.
89. H.Lei, S.P.Oh, M.Okano, R.Juttermann, K.A.Goss, R.Jaenisch, E.Li 1996. De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. Development. 122:3195–3205.
90. H.G.Leitch, W.W.Tang, M.A.Surani 2013. Primordial germ-cell development and epigenetic reprogramming in mammals. Curr Top Dev Biol. 104:149–187.
91. M.Leseva, B.B.Knowles, D.M.Messerschmidt, D.Solter 2016. Erase-maintain-establish:natural reprogramming of the mammalian epigenome. Cold Spring Harb Symp Quant Biol. [Epub ahead of print]. DOI:10.1101/sqb.2015.80.027441.
92. Y.W.Leu, P.Y.Chu, C.M.Chen, K.T.Yeh, Y.M.Liu, Y.H.Lee, S.T.Kuo, S.H.Hsiao 2014. Early life ethanol exposure causes long-lasting disturbances in rat mesenchymal stem cells via epigenetic modifications. Biochem Biophys Res Commun. 453:338–344.
93. E.Li, T.H.Bestor, R.Jaenisch 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell. 69:915–926.
94. F.Li, Y.Xiao, F.Huang, W.Deng, H.Zhao, X.Shi, S.Wang, X.Yu, L.Zhang, Z.Han,. 2015. Spatiotemporal-specific lncRNAs in the brain, colon, liver and lung of macaque during development. Mol Biosyst. 11:3253–3263.
95. G.Li, H.Wang, A.B.Liu, C.Cheung, K.R.Reuhl, M.C.Bosland, C.S.Yang 2012a. Dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced prostate carcinogenesis in CYP1A-humanized mice. Cancer Prev Res (Philadelphia, Pa). 5:963–972.
96. Y.Li, D.Xiao, C.Dasgupta, F.Xiong, W.Tong, S.Yang, L.Zhang 2012b. Perinatal nicotine exposure increases vulnerability of hypoxic-ischemic brain injury in neonatal rats:role of angiotensin II receptors. Stroke. 43:2483–2490.
97. Y.Li, D.Xiao, S.Yang, L.Zhang 2013. Promoter methylation represses AT2R gene and increases brain hypoxic-ischemic injury in neonatal rats. Neurobiol Dis. 60:32–38.
98. S.Lie, J.L.Morrison, O.Williams-Wyss, C.M.Suter, D.T.Humphreys, S.E.Ozanne, S.Zhang, S.M.Mac Laughlin, D.O.Kleemann, S.K.Walker,. 2014a. Impact of embryo number and maternal undernutrition around the time of conception on insulin signaling and gluconeogenic factors and microRNAs in the liver of fetal sheep. Am J Physiol Endocrinol Metab. 306:E1013–E1024.
99. S.Lie, J.L.Morrison, O.Williams-Wyss, C.M.Suter, D.T.Humphreys, S.E.Ozanne, S.Zhang, S.M.Maclaughlin, D.O.Kleemann, S.K.Walker,. 2014b. Periconceptional undernutrition programs changes in insulin-signaling molecules and microRNAs in skeletal muscle in singleton and twin fetal sheep. Biol Reprod. 90:5. DOI:10.1095/biolreprod.113.109751.
100. R.K.Lin, Y.S.Hsieh, P.Lin, H.S.Hsu, C.Y.Chen, Y.A.Tang, C.F.Lee, Y.C.Wang 2010. The tobacco-specific carcinogen NNK induces DNA methyltransferase 1 accumulation and tumor suppressor gene hypermethylation in mice and lung cancer patients. J Clin Invest. 120:521–532.
101. J.O.Linschooten, F.J.Van Schooten, A.Baumgartner, E.Cemeli, J.Van Delft, D.Anderson, R.W.Godschalk 2009. Use of spermatozoal mRNA profiles to study gene-environment interactions in human germ cells. Mutat Res. 667:m76.
102. W.Liu, Z.Niu, Q.Li, R.T.Pang, P.C.Chiu, W.S.Yeung 2016. MicroRNA and embryo implantation. Am J Reprod Immunol. 75:263–271.
103. W.M.Liu, R.T.Pang, P.C.Chiu, B.P.Wong, K.Lao, K.F.Lee, W.S.Yeung 2012. Sperm-borne microRNA-34c is required for the first cleavage division in mouse. Proc Natl Acad Sci U.S.A. 109:490–494.
104. A.C.Luk, W.Y.Chan, O.M.Rennert, T.L.Lee 2014. Long noncoding RNAs in spermatogenesis:insights from recent high-throughput transcriptome studies. Reproduction. 147:R131–R141.
105. L.H.Lumey, A.D.Stein, E.Susser 2011. Prenatal famine and adult health. Annu Rev Public Health. 32:237–262.
106. C.Marcho, W.Cui, J.Mager 2015. Epigenetic dynamics during preimplantation development. Reproduction. 150:R109–R120.
107. E.L.Marczylo, A.A.Amoako, J.C.Konje, T.W.Gant, T.H.Marczylo 2012. Smoking induces differential miRNA expression in human spermatozoa:a potential transgenerational epigenetic concern? Epigenetics. 7:432–439.
108. D.B.Martinez-Arguelles, M.Culty, B.R.Zirkin, V.Papadopoulos 2009. In utero exposure to di-(2-ethylhexyl) phthalate decreases mineralocorticoid receptor expression in the adult testis. Endocrinology. 150:5575–5585.
109. J.A.Marwick, P.A.Kirkham, C.S.Stevenson, H.Danahay, J.Giddings, K.Butler, K.Donaldson, W.Macnee, I.Rahman 2004. Cigarette smoke alters chromatin remodeling and induces proinflammatory genes in rat lungs. Am J Respir Cell Mol Biol. 31:633–642.
110. J.S.Mattick 2007. A new paradigm for developmental biology. J Exp Biol. 210:1526–1547.
111. J.McGrath, D.Solter 1984. Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell. 37:179–183.
112. T.Melkamu, X.Zhang, J.Tan, Y.Zeng, F.Kassie 2010. Alteration of microRNA expression in vinyl carbamate-induced mouse lung tumors and modulation by the chemopreventive agent indole-3-carbinol. Carcinogenesis. 31:252–258.
113. D.M.Messerschmidt 2016. A twist in zygotic reprogramming. Nat Cell Biol. 18:139–140.
114. D.M.Messerschmidt, B.B.Knowles, D.Solter 2014. DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes Dev. 28:812–828.
115. C.Metzler-Guillemain, G.Victorero, C.Lepoivre, A.Bergon, M.Yammine, J.Perrin, I.Sari-Minodier, N.Boulanger, P.Rihet, C.Nguyen 2015. Sperm mRNAs and microRNAs as candidate markers for the impact of toxicants on human spermatogenesis:an application to tobacco smoking. Syst Biol Reprod Med. 61:139–149.
116. F.A.Middleton, E.I.Varlinskaya, S.M.Mooney 2012. Molecular substrates of social avoidance seen following prenatal ethanol exposure and its reversal by social enrichment. Dev Neurosci. 34:115–128.
117. D.Miller, M.Brinkworth, D.Iles 2010. Paternal DNA packaging in spermatozoa:more than the sum of its parts? DNA, histones, protamines and epigenetics. Reproduction. 139:287–301.
118. I.R.Miousse, R.Currie, K.Datta, H.Ellinger-Ziegelbauer, J.E.French, A.H.Harrill, I.Koturbash, M.Lawton, D.Mann, R.R.Meehan,. 2015. Importance of investigating epigenetic alterations for industry and regulators:an appraisal of current efforts by the Health and Environmental Sciences Institute. Toxicology. 335:11–19.
119. Y.Mishima 2012. Widespread roles of microRNAs during zebrafish development and beyond. Dev Growth Differ. 54:55–65.
120. Y.Motorin, F.Lyko, M.Helm 2010. 5-Methylcytosine in RNA:detection, enzymatic formation and biological functions. Nucleic Acids Res. 38:1415–1430.
121. A.Moussaieff, M.Rouleau, D.Kitsberg, M.Cohen, G.Levy, D.Barasch, A.Nemirovski, S.Shen-Orr, I.Laevsky, M.Amit,. 2015. Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells. Cell Metab. 21:392–402.
122. A.Mukherjee, S.Koli, K.V.Reddy 2014. Regulatory non-coding transcripts in spermatogenesis:shedding light on 'dark matter'. Andrology. 2:360–369.
123. R.Nishihara, T.Morikawa, A.Kuchiba, P.Lochhead, M.Yamauchi, X.Liao, Y.Imamura, K.Nosho, K.Shima, I.Kawachi,. 2013. A prospective study of duration of smoking cessation and colorectal cancer risk by epigenetics-related tumor classification. Am J Epidemiol. 178:84–100.
124. D.Noble 2006. The music of life biology beyond genes. New York:Oxford University Press.
125. A.M.O'Doherty, P.A.McGettigan 2014. Epigenetic processes in the male germline. Reprod Fertil Dev. 27:725–738.
126. OECD. 2012. Guidance document on standardised test guidelines for evaluating chemicals for endocrine disruption. France:OECD Publishing.
127. OECD. 2014. Detailed review paper on the state of the science on novel in vitro and in vivo screening and testing methods and endpoints for evaluating endocrine disruptors. France:OECD Publishing.
128. Y.Ohnishi, Y.Totoki, A.Toyoda, T.Watanabe, Y.Yamamoto, K.Tokunaga, Y.Sakaki, H.Sasaki, H.Hohjoh 2010. Small RNA class transition from siRNA/piRNA to miRNA during pre-implantation mouse development. Nucleic Acids Res. 38:5141–5151.
129. M.Okano, D.W.Bell, D.A.Haber, E.Li 1999. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 99:247–257.
130. M.Okano, S.Xie, E.Li 1998. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet. 19:219–220.
131. N.Onishchenko, N.Karpova, F.Sabri, E.Castren, S.Ceccatelli 2008. Long-lasting depression-like behavior and epigenetic changes of BDNF gene expression induced by perinatal exposure to methylmercury. J Neurochem. 106:1378–1387.
132. K.L.Ostrow, C.Michailidi, R.Guerrero-Preston, M.O.Hoque, A.Greenberg, W.Rom, D.Sidransky 2013. Cigarette smoke induces methylation of the tumor suppressor gene NISCH. Epigenetics. 8:383–388.
133. P.A.Padilla, A.M.Garcia, M.L.Ladage, L.S.Toni 2014. Caenorhabditis elegans:an old genetic model can learn new epigenetic tricks. Integr Comp Biol. 54:52–60.
134. M.Pandey, S.Sahay, P.Tiwari, D.S.Upadhyay, S.Sultana, K.P.Gupta 2014a. Involvement of EZH2, SUV39H1, G9a and associated molecules in pathogenesis of urethane induced mouse lung tumors:potential targets for cancer control. Toxicol Appl Pharmacol. 280:296–304.
135. M.Pandey, S.Sultana, K.P.Gupta 2014b. Involvement of epigenetics and microRNA-29b in the urethane induced inception and establishment of mouse lung tumors. Exp Mol Pathol. 96:61–70.
136. L.Pantano, M.Jodar, M.Bak, J.L.Ballesca, N.Tommerup, R.Oliva, T.Vavouri 2015. The small RNA content of human sperm reveals pseudogene-derived piRNAs complementary to protein-coding genes. RNA. 21:1085–1095.
137. A.J.Papoutsis, O.I.Selmin, J.L.Borg, D.F.Romagnolo 2015. Gestational exposure to the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin induces BRCA-1 promoter hypermethylation and reduces BRCA-1 expression in mammary tissue of rat offspring:preventive effects of resveratrol. Mol Carcinog. 54:261–269.
138. M.Pascual, P.Balino, S.Alfonso-Loeches, C.M.Aragon, C.Guerri 2011. Impact of TLR4 on behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage. Brain Behav Immun. 25:S80–S91.
139. S.Paul, N.Banerjee, A.Chatterjee, T.J.Sau, J.K.Das, P.K.Mishra, P.Chakrabarti, A.Bandyopadhyay, A.K.Giri 2014. Arsenic-induced promoter hypomethylation and over-expression of ERCC2 reduces DNA repair capacity in humans by non-disjunction of the ERCC2-Cdk7 complex. Metallom:Integrated Biometal Sci. 6:864–873.
140. M.Pembrey, R.Saffery, L.O.Bygren 2014. Human transgenerational responses to early-life experience:potential impact on development, health and biomedical research. J Med Genet. 51:563–572.
141. C.Peng, W.Zhang, W.Zhao, J.Zhu, X.Huang, J.Tian 2015. Alcohol-induced histone H3K9 hyperacetylation and cardiac hypertrophy are reversed by a histone acetylases inhibitor anacardic acid in developing murine hearts. Biochimie. 113:1–9.
142. L.C.Pulling, B.R.Vuillemenot, J.A.Hutt, T.R.Devereux, S.A.Belinsky 2004. Aberrant promoter hypermethylation of the death-associated protein kinase gene is early and frequent in murine lung tumors induced by cigarette smoke and tobacco carcinogens. Cancer Res. 64:3844–3848.
143. M.P.Ramos, N.A.Wijetunga, A.S.McLellan, M.Suzuki, J.M.Greally 2015. DNA demethylation by 5-aza-2'-deoxycytidine is imprinted, targeted to euchromatin, and has limited transcriptional consequences. Epigenet Chromat. 8:11. DOI:10.1186/s13072-015-0004-x.
144. M.Rassoulzadegan, V.Grandjean, P.Gounon, S.Vincent, I.Gillot, F.Cuzin 2006. RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature. 441:469–474.
145. A.B.Rodgers, C.P.Morgan, S.L.Bronson, S.Revello, T.L.Bale 2013. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. J Neurosci. 33:9003–9012.
146. A.B.Rodgers, C.P.Morgan, N.A.Leu, T.L.Bale 2015. Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress. Proc Natl Acad Sci USA. 112:13699–13704.
147. C.S.Rosenfeld 2010. Animal models to study environmental epigenetics. Biol Reprod. 82:473–488.
148. C.S.Rosenfeld, P.T.Sieli, D.A.Warzak, M.R.Ellersieck, K.A.Pennington, R.M.Roberts 2013. Maternal exposure to bisphenol A and genistein has minimal effect on A(vy)/a offspring coat color but favors birth of agouti over nonagouti mice. Proc Natl Acad Sci USA. 110:537–542.
149. A.Ruiz-Hernandez, C.C.Kuo, P.Rentero-Garrido, W.Y.Tang, J.Redon, J.M.Ordovas, A.Navas-Acien, M.Tellez-Plaza 2015. Environmental chemicals and DNA methylation in adults:a systematic review of the epidemiologic evidence. Clin Epigenet. 7:55. DOI:10.1186/s13148-015-0055-7.
150. P.A.Rzeczkowska, H.Hou, M.D.Wilson, M.R.Palmert 2014. Epigenetics:a new player in the regulation of mammalian puberty. Neuroendocrinology. 99:139–155.
151. S.Schneider, W.Kaufmann, R.Buesen, B.van Ravenzwaay 2008. Vinclozolin-the lack of a transgenerational effect after oral maternal exposure during organogenesis. Reprod Toxicol. 25:352–360.
152. S.Schneider, H.Marxfeld, S.Groters, R.Buesen, B.van Ravenzwaay 2013. Vinclozolin–no transgenerational inheritance of anti-androgenic effects after maternal exposure during organogenesis via the intraperitoneal route. Reprod Toxicol. 37:6–14.
153. S.Seisenberger, S.Andrews, F.Krueger, J.Arand, J.Walter, F.Santos, C.Popp, B.Thienpont, W.Dean, W.Reik 2012. The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol Cell. 48:849–862.
154. U.Sharma, C.C.Conine, J.M.Shea, A.Boskovic, A.G.Derr, X.Y.Bing, C.Belleannee, A.Kucukural, R.W.Serra, F.Sun,. 2016. Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science. 351:391–396.
155. N.S.Shenker, S.Polidoro, K.van Veldhoven, C.Sacerdote, F.Ricceri, M.A.Birrell, M.G.Belvisi, R.Brown, P.Vineis, J.M.Flanagan 2013. Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking. Hum Mol Genet. 22:843–851.
156. R.C.Slieker, M.S.Roost, L.van Iperen, H.E.Suchiman, E.W.Tobi, F.Carlotti, E.J.de Koning, P.E.Slagboom, B.T.Heijmans, S.M.Chuva de Sousa Lopes 2015. DNA methylation landscapes of human fetal development. PLoS Genet. 11:e1005583.
157. R.A.Somer, C.S.Thummel 2014. Epigenetic inheritance of metabolic state. Curr Opin Genet Dev. 27:43–47.
158. H.K.Somineni, X.Zhang, J.M.Biagini Myers, M.B.Kovacic, A.Ulm, N.Jurcak, P.H.Ryan, G.K.Khurana Hershey, H.Ji 2016. Ten-eleven translocation 1 (TET1) methylation is associated with childhood asthma and traffic-related air pollution. J Allergy Clin Immunol. 137:797–805.e795.
159. Y.Song, C.Liu, Y.Hui, K.Srivastava, Z.Zhou, J.Chen, R.L.Miller, F.D.Finkelman, X.M.Li 2014. Maternal allergy increases susceptibility to offspring allergy in association with TH2-biased epigenetic alterations in a mouse model of peanut allergy. J Allergy Clin Immunol. 134:1339–1345.e7.
160. B.D.Strahl, C.D.Allis 2000. The language of covalent histone modifications. Nature. 403:41–45.
161. T.Suganuma, J.L.Workman 2011. Signals and combinatorial functions of histone modifications. Annu Rev Biochem. 80:473–499.
162. N.Suh, R.Blelloch 2011. Small RNAs in early mammalian development:from gametes to gastrulation. Development. 138:1653–1661.
163. W.Sun, M.Guan, X.Li 2014. 5-Hydroxymethylcytosine-mediated DNA demethylation in stem cells and development. Stem Cells Dev. 23:923–930.
164. M.A.Surani 2015. Human germline:a new research frontier. Stem Cell Rep. 4:955–960.
165. M.Susiarjo, F.Xin, A.Bansal, M.Stefaniak, C.Li, R.A.Simmons, M.S.Bartolomei 2015. Bisphenol a exposure disrupts metabolic health across multiple generations in the mouse. Endocrinology. 156:2049–2058.
166. M.Tahiliani, K.P.Koh, Y.Shen, W.A.Pastor, H.Bandukwala, Y.Brudno, S.Agarwal, L.M.Iyer, D.R.Liu, L.Aravind,. 2009. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 324:930–935.
167. T.Takeda, M.Fujii, J.Taura, Y.Ishii, H.Yamada 2012. Dioxin silences gonadotropin expression in perinatal pups by inducing histone deacetylases:a new insight into the mechanism for the imprinting of sexual immaturity by dioxin. J Biol Chem. 287:18440–18450.
168. W.W.Tang, S.Dietmann, N.Irie, H.G.Leitch, V.I.Floros, C.R.Bradshaw, J.A.Hackett, P.F.Chinnery, M.A.Surani 2015. A unique gene regulatory network resets the human germline epigenome for development. Cell. 161:1453–1467.
169. L.Tao, R.Ge, M.Xie, P.M.Kramer, M.A.Pereira 1999. Effect of trichloroethylene on DNA methylation and expression of early-intermediate protooncogenes in the liver of B6C3F1 mice. J Biochem Mol Toxicol. 13:231–237.
170. L.Tao, P.M.Kramer, R.Ge, M.A.Pereira 1998. Effect of dichloroacetic acid and trichloroacetic acid on DNA methylation in liver and tumors of female B6C3F1 mice. Toxicol Sci. 43:139–144.
171. D.H.Taylor, E.T.Chu, R.Spektor, P.D.Soloway 2015. Long non-coding RNA regulation of reproduction and development. Mol Reprod Dev. 82:932–956.
172. Z.Tong, C.Han, W.Luo, H.Li, H.Luo, M.Qiang, T.Su, B.Wu, Y.Liu, X.Yang,. 2013. Aging-associated excess formaldehyde leads to spatial memory deficits. Sci Rep. 3:1807.
173. Z.Tong, C.Han, M.Qiang, W.Wang, J.Lv, S.Zhang, W.Luo, H.Li, H.Luo, J.Zhou,. 2015. Age-related formaldehyde interferes with DNA methyltransferase function, causing memory loss in Alzheimer's disease. Neurobiol Aging. 36:100–110.
174. L.S.Trevino, Q.Wang, C.L.Walker 2015. Phosphorylation of epigenetic “‘readers, writers and erasers':implications for developmental reprogramming and the epigenetic basis for health and disease”. Prog Biophys Mol Biol. 118:8–13.
175. V.P.Tryndyak, A.K.Marrone, J.R.Latendresse, L.Muskhelishvili, F.A.Beland, I.P.Pogribny 2016. MicroRNA changes, activation of progenitor cells and severity of liver injury in mice induced by choline and folate deficiency. J Nutr Biochem. 28:83–90.
176. B.M.Turner 2000. Histone acetylation and an epigenetic code. Bioessays. 22:836–845.
177. E.Tyagi, Y.Zhuang, R.Agrawal, Z.Ying, F.Gomez-Pinilla 2015. Interactive actions of Bdnf methylation and cell metabolism for building neural resilience under the influence of diet. Neurobiol Dis. 73:307–318.
178. B.van Ravenzwaay, J.Kleinjans, H.Vrijhof 2014. Editorial-epigenetics and chemical safety. Mutat Res Genet Toxicol Environ Mutagen. 764–765:1–2.
179. Z.Vucetic, J.Kimmel, K.Totoki, E.Hollenbeck, T.M.Reyes 2010. Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes. Endocrinology. 151:4756–4764.
180. B.R.Vuillemenot, L.C.Pulling, W.A.Palmisano, J.A.Hutt, S.A.Belinsky 2004. Carcinogen exposure differentially modulates RAR-beta promoter hypermethylation, an early and frequent event in mouse lung carcinogenesis. Carcinogenesis. 25:623–629.
181. P.D.Wadhwa, C.Buss, S.Entringer, J.M.Swanson 2009. Developmental origins of health and disease:brief history of the approach and current focus on epigenetic mechanisms. Semin Reprod Med. 27:358–368.
182. K.D.Wagner, N.Wagner, H.Ghanbarian, V.Grandjean, P.Gounon, F.Cuzin, M.Rassoulzadegan 2008. RNA induction and inheritance of epigenetic cardiac hypertrophy in the mouse. Dev Cell. 14:962–969.
183. B.Wang, Y.Li, Y.Tan, X.Miao, X.D.Liu, C.Shao, X.H.Yang, S.Turdi, L.J.Ma, J.Ren,. 2012. Low-dose Cd induces hepatic gene hypermethylation, along with the persistent reduction of cell death and increase of cell proliferation in rats and mice. PLoS One. 7:e33853.
184. X.Wang, H.Wang 2013. Epigenotoxicity of environmental pollutants evaluated by a combination of DNA methylation inhibition and capillary electrophoresis-laser-induced fluorescence immunoassay. Anal Bioanal Chem. 405:2435–2442.
185. Y.Wang, M.Dasso 2009. SUMOylation and deSUMOylation at a glance. J Cell Sci. 122:4249–4252.
186. M.Warner, P.Mocarelli, P.Brambilla, A.Wesselink, S.Samuels, S.Signorini, B.Eskenazi 2013. Diabetes, metabolic syndrome, and obesity in relation to serum dioxin concentrations:the Seveso women's health study. Environ Health Perspect. 121:906–911.
187. M.Warner, P.Mocarelli, S.Samuels, L.Needham, P.Brambilla, B.Eskenazi 2011. Dioxin exposure and cancer risk in the Seveso Women's Health Study. Environ Health Perspect. 119:1700–1705.
188. T.Watanabe, A.Takeda, T.Tsukiyama, K.Mise, T.Okuno, H.Sasaki, N.Minami, H.Imai 2006. Identification and characterization of two novel classes of small RNAs in the mouse germline:retrotransposon-derived siRNAs in oocytes and germline small RNAs in testes. Genes Dev. 20:1732–1743.
189. T.Watanabe, S.Tomizawa, K.Mitsuya, Y.Totoki, Y.Yamamoto, S.Kuramochi-Miyagawa, N.Iida, Y.Hoki, P.J.Murphy, A.Toyoda,. 2011. Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science. 332:848–852.
190. T.Watanabe, Y.Totoki, A.Toyoda, M.Kaneda, S.Kuramochi-Miyagawa, Y.Obata, H.Chiba, Y.Kohara, T.Kono, T.Nakano,. 2008. Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature. 453:539–543.
191. R.A.Waterland, D.C.Dolinoy, J.R.Lin, C.A.Smith, X.Shi, K.G.Tahiliani 2006. Maternal methyl supplements increase offspring DNA methylation at Axin Fused. Genesis. 44:401–406.
192. K.E.Wellen, G.Hatzivassiliou, U.M.Sachdeva, T.V.Bui, J.R.Cross, C.B.Thompson 2009. ATP-citrate lyase links cellular metabolism to histone acetylation. Science. 324:1076–1080.
193. T.D.Williams, L.Mirbahai, J.K.Chipman 2014. The toxicological application of transcriptomics and epigenomics in zebrafish and other teleosts. Brief Funct Genomics. 13:157–171.
194. Z.Williams, P.Morozov, A.Mihailovic, C.Lin, P.K.Puvvula, S.Juranek, Z.Rosenwaks, T.Tuschl 2015. Discovery and characterization of piRNAs in the human fetal ovary. Cell Rep. 13:854–863.
195. R.L.Wong, Q.Wang, L.S.Trevino, M.C.Bosland, J.Chen, M.Medvedovic, G.S.Prins, K.Kannan, S.M.Ho, C.L.Walker 2015. Identification of secretaglobin Scgb2a1 as a target for developmental reprogramming by BPA in the rat prostate. Epigenetics. 10:127–134.
196. J.Wu, M.R.Basha, B.Brock, D.P.Cox, F.Cardozo-Pelaez, C.A.McPherson, J.Harry, D.C.Rice, B.Maloney, D.Chen,. 2008. Alzheimer's disease (AD)-like pathology in aged monkeys after infantile exposure to environmental metal lead (Pb):evidence for a developmental origin and environmental link for AD. J Neurosci. 28:3–9.
197. Q.Wu, S.Ohsako, R.Ishimura, J.S.Suzuki, C.Tohyama 2004. Exposure of mouse preimplantation embryos to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters the methylation status of imprinted genes H19 and Igf2. Biol Reprod. 70:1790–1797.
198. L.Xie, M.Wu, H.Lin, C.Liu, H.Yang, J.Zhan, S.Sun 2014. An increased ratio of serum miR-21 to miR-181a levels is associated with the early pathogenic process of chronic obstructive pulmonary disease in asymptomatic heavy smokers. Mol Biosyst. 10:1072–1081.
199. Y.E.Yan, L.Liu, J.F.Wang, F.Liu, X.H.Li, H.Q.Qin, H.Wang 2014. Prenatal nicotinic exposure suppresses fetal adrenal steroidogenesis via steroidogenic factor 1 (SF-1) deacetylation. Toxicol Appl Pharmacol. 277:231–241.
200. P.Yang, J.Ma, B.Zhang, H.Duan, Z.He, J.Zeng, X.Zeng, D.Li, Q.Wang, Y.Xiao,. 2012. CpG site-specific hypermethylation of p16INK4alpha in peripheral blood lymphocytes of PAH-exposed workers. Cancer Epidemiol Biomarkers Prev. 21:182–190.
201. S.R.Yang, S.Valvo, H.Yao, A.Kode, S.Rajendrasozhan, I.Edirisinghe, S.Caito, D.Adenuga, R.Henry, G.Fromm,. 2008. IKK alpha causes chromatin modification on pro-inflammatory genes by cigarette smoke in mouse lung. Am J Respir Cell Mol Biol. 38:689–698.
202. W.Yoshioka, W.Higashiyama, C.Tohyama 2011. Involvement of microRNAs in dioxin-induced liver damage in the mouse. Toxicol Sci. 122:457–465.
203. S.Yuan, A.Schuster, C.Tang, T.Yu, N.Ortogero, J.Bao, H.Zheng, W.Yan 2016. Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development. Development. 143:635–647.
204. M.Zeybel, T.Hardy, Y.K.Wong, J.C.Mathers, C.R.Fox, A.Gackowska, F.Oakley, A.D.Burt, C.L.Wilson, Q.M.Anstee,. 2012. Multigenerational epigenetic adaptation of the hepatic wound-healing response. Nat Med. 18:1369–1377.
205. J.Zhang, Y.Zhou, L.Ma, S.Huang, R.Wang, R.Gao, Y.Wu, H.Shi, J.Zhang 2013. The alteration of miR-222 and its target genes in nickel-induced tumor. Biol Trace Elem Res. 152:267–274.
206. P.Zhang, J.Y.Kang, L.T.Gou, J.Wang, Y.Xue, G.Skogerboe, P.Dai, D.W.Huang, R.Chen, X.D.Fu,. 2015. MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes. Cell Res. 25:193–207.
207. R.Zhou, F.Chen, F.Chang, Y.Bai, L.Chen 2013. Persistent overexpression of DNA methyltransferase 1 attenuating GABAergic inhibition in basolateral amygdala accounts for anxiety in rat offspring exposed perinatally to low-dose bisphenol A. J Psychiatr Res. 47:1535–1544.