NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure
Autoři:
Patrick J. Murphy aff001; Jingtao Guo aff002; Timothy G. Jenkins aff003; Emma R. James aff003; John R. Hoidal aff005; Thomas Huecksteadt aff005; Dallin S. Broberg aff003; James M. Hotaling aff003; David F. Alonso aff006; Douglas T. Carrell aff003; Bradley R. Cairns aff002; Kenneth I. Aston aff003
Působiště autorů:
Department of Biomedical Genetics, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, United States of America
aff001; Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, United States of America
aff002; Andrology and IVF Laboratories, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah, United States of America
aff003; Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah, United States of America
aff004; Department of Internal Medicine, University of Utah School of Medicine and Salt Lake VA Medical Center, Salt Lake City, Utah, United States of America
aff005; Department of Psychology, University of Utah, Salt Lake City, Utah, United States of America
aff006; Department of Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United States of America
aff007
Vyšlo v časopise:
NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008756
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008756
Souhrn
Paternal cigarette smoke (CS) exposure is associated with increased risk of behavioral disorders and cancer in offspring, but the mechanism has not been identified. Here we use mouse models to investigate mechanisms and impacts of paternal CS exposure. We demonstrate that CS exposure induces sperm DNAme changes that are partially corrected within 28 days of removal from CS exposure. Additionally, paternal smoking is associated with changes in prefrontal cortex DNAme and gene expression patterns in offspring. Remarkably, the epigenetic and transcriptional effects of CS exposure that we observed in wild type mice are partially recapitulated in Nrf2-/- mice and their offspring, independent of smoking status. Nrf2 is a central regulator of antioxidant gene transcription, and mice lacking Nrf2 consequently display elevated oxidative stress, suggesting that oxidative stress may underlie CS-induced heritable epigenetic changes. Importantly, paternal sperm DNAme changes do not overlap with DNAme changes measured in offspring prefrontal cortex, indicating that the observed DNAme changes in sperm are not directly inherited. Additionally, the changes in sperm DNAme associated with CS exposure were not observed in sperm of unexposed offspring, suggesting the effects are likely not maintained across multiple generations.
Klíčová slova:
DNA methylation – Epigenetics – Gene expression – Mouse models – Oxidative stress – Prefrontal cortex – Smoking habits – Sperm
Zdroje
1. Oberg M, Jaakkola MS, Woodward A, Peruga A, Pruss-Ustun A. Worldwide burden of disease from exposure to second-hand smoke: a retrospective analysis of data from 192 countries. Lancet. 2011;377(9760):139–46. Epub 2010/11/30. doi: 10.1016/S0140-6736(10)61388-8 21112082.
2. DiFranza JR, Aligne CA, Weitzman M. Prenatal and postnatal environmental tobacco smoke exposure and children's health. Pediatrics. 2004;113(4 Suppl):1007–15. Epub 2004/04/03. 15060193.
3. Moritsugu KP. The 2006 Report of the Surgeon General: the health consequences of involuntary exposure to tobacco smoke. Am J Prev Med. 2007;32(6):542–3. Epub 2007/05/30. doi: 10.1016/j.amepre.2007.02.026 17533072.
4. Laubenthal J, Zlobinskaya O, Poterlowicz K, Baumgartner A, Gdula MR, Fthenou E, et al. Cigarette smoke-induced transgenerational alterations in genome stability in cord blood of human F1 offspring. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2012;26(10):3946–56. Epub 2012/06/26. doi: 10.1096/fj.11-201194 22730438.
5. Rolland M, Le Moal J, Wagner V, Royere D, De Mouzon J. Decline in semen concentration and morphology in a sample of 26 609 men close to general population between 1989 and 2005 in France. Human reproduction. 2012. Epub 2012/12/06. doi: 10.1093/humrep/des415 23213178.
6. Priskorn L, Holmboe SA, Jacobsen R, Jensen TK, Lassen TH, Skakkebaek NE. Increasing trends in childlessness in recent birth cohorts—a registry-based study of the total Danish male population born from 1945 to 1980. International journal of andrology. 2012;35(3):449–55. Epub 2012/04/12. doi: 10.1111/j.1365-2605.2012.01265.x 22489560.
7. Swan SH, Elkin EP, Fenster L. Have sperm densities declined? A reanalysis of global trend data. Environmental health perspectives. 1997;105(11):1228–32. Epub 1998/02/12. doi: 10.1289/ehp.971051228 9370524; PubMed Central PMCID: PMC1470335.
8. Kiziler AR, Aydemir B, Onaran I, Alici B, Ozkara H, Gulyasar T, et al. High levels of cadmium and lead in seminal fluid and blood of smoking men are associated with high oxidative stress and damage in infertile subjects. Biological trace element research. 2007;120(1–3):82–91. Epub 2007/10/06. doi: 10.1007/s12011-007-8020-8 17916958.
9. Kulikauskas V, Blaustein D, Ablin RJ. Cigarette smoking and its possible effects on sperm. Fertility and sterility. 1985;44(4):526–8. Epub 1985/10/01. doi: 10.1016/s0015-0282(16)48925-9 4054326.
10. Polyzos A, Schmid TE, Pina-Guzman B, Quintanilla-Vega B, Marchetti F. Differential sensitivity of male germ cells to mainstream and sidestream tobacco smoke in the mouse. Toxicology and applied pharmacology. 2009;237(3):298–305. Epub 2009/04/07. doi: 10.1016/j.taap.2009.03.019 19345701.
11. Fuentes A, Munoz A, Barnhart K, Arguello B, Diaz M, Pommer R. Recent cigarette smoking and assisted reproductive technologies outcome. Fertility and sterility. 2010;93(1):89–95. Epub 2008/11/01. doi: 10.1016/j.fertnstert.2008.09.073 18973890.
12. Marchetti F, Rowan-Carroll A, Williams A, Polyzos A, Berndt-Weis ML, Yauk CL. Sidestream tobacco smoke is a male germ cell mutagen. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(31):12811–4. Epub 2011/07/20. doi: 10.1073/pnas.1106896108 21768363; PubMed Central PMCID: PMC3150936.
13. Secretan B, Straif K, Baan R, Grosse Y, El Ghissassi F, Bouvard V, et al. A review of human carcinogens—Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol. 2009;10(11):1033–4. Epub 2009/11/06. doi: 10.1016/s1470-2045(09)70326-2 19891056.
14. Kohli A, Garcia MA, Miller RL, Maher C, Humblet O, Hammond SK, et al. Secondhand smoke in combination with ambient air pollution exposure is associated with increasedx CpG methylation and decreased expression of IFN-gamma in T effector cells and Foxp3 in T regulatory cells in children. Clin Epigenetics. 2012;4(1):17. Epub 2012/09/27. doi: 10.1186/1868-7083-4-17 23009259; PubMed Central PMCID: PMC3483214.
15. Bosse Y, Postma DS, Sin DD, Lamontagne M, Couture C, Gaudreault N, et al. Molecular signature of smoking in human lung tissues. Cancer research. 2012;72(15):3753–63. Epub 2012/06/05. doi: 10.1158/0008-5472.CAN-12-1160 22659451.
16. Word B, Lyn-Cook LE Jr., Mwamba B, Wang H, Lyn-Cook B, Hammons G. Cigarette Smoke Condensate Induces Differential Expression and Promoter Methylation Profiles of Critical Genes Involved in Lung Cancer in NL-20 Lung Cells In Vitro: Short-Term and Chronic Exposure. International journal of toxicology. 2012. Epub 2012/11/24. doi: 10.1177/1091581812465902 23174910.
17. Breton CV, Byun HM, Wenten M, Pan F, Yang A, Gilliland FD. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am J Respir Crit Care Med. 2009;180(5):462–7. Epub 2009/06/06. doi: 10.1164/rccm.200901-0135OC 19498054; PubMed Central PMCID: PMC2742762.
18. Perera F, Herbstman J. Prenatal environmental exposures, epigenetics, and disease. Reproductive toxicology. 2011;31(3):363–73. Epub 2011/01/25. doi: 10.1016/j.reprotox.2010.12.055 21256208; PubMed Central PMCID: PMC3171169.
19. Joubert BR, Haberg SE, Nilsen RM, Wang X, Vollset SE, Murphy SK, et al. 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environmental health perspectives. 2012;120(10):1425–31. Epub 2012/08/02. doi: 10.1289/ehp.1205412 22851337; PubMed Central PMCID: PMC3491949.
20. Jenkins TG, James ER, Alonso DF, Hoidal JR, Murphy PJ, Hotaling JM, et al. Cigarette smoking significantly alters sperm DNA methylation patterns. Andrology. 2017. doi: 10.1111/andr.12416 28950428.
21. Grundberg E, Meduri E, Sandling JK, Hedman AK, Keildson S, Buil A, et al. Global analysis of DNA methylation variation in adipose tissue from twins reveals links to disease-associated variants in distal regulatory elements. Am J Hum Genet. 2013;93(5):876–90. Epub 2013/11/05. doi: 10.1016/j.ajhg.2013.10.004 24183450; PubMed Central PMCID: PMC3824131.
22. Busche S, Shao X, Caron M, Kwan T, Allum F, Cheung WA, et al. Population whole-genome bisulfite sequencing across two tissues highlights the environment as the principal source of human methylome variation. Genome Biol. 2015;16:290. Epub 2015/12/25. doi: 10.1186/s13059-015-0856-1 26699896; PubMed Central PMCID: PMC4699357.
23. Petersen AK, Zeilinger S, Kastenmuller G, Romisch-Margl W, Brugger M, Peters A, et al. Epigenetics meets metabolomics: an epigenome-wide association study with blood serum metabolic traits. Hum Mol Genet. 2014;23(2):534–45. Epub 2013/09/10. doi: 10.1093/hmg/ddt430 24014485; PubMed Central PMCID: PMC3869358.
24. Irvin MR, Zhi D, Joehanes R, Mendelson M, Aslibekyan S, Claas SA, et al. Epigenome-wide association study of fasting blood lipids in the Genetics of Lipid-lowering Drugs and Diet Network study. Circulation. 2014;130(7):565–72. Epub 2014/06/13. doi: 10.1161/CIRCULATIONAHA.114.009158 24920721; PubMed Central PMCID: PMC4209699.
25. Dai J, Wang Z, Xu W, Zhang M, Zhu Z, Zhao X, et al. Paternal nicotine exposure defines different behavior in subsequent generation via hyper-methylation of mmu-miR-15b. Sci Rep. 2017;7(1):7286. Epub 2017/08/06. doi: 10.1038/s41598-017-07920-3 28779169; PubMed Central PMCID: PMC5544724.
26. Hawkey AB, White H, Pippen E, Greengrove E, Rezvani AH, Murphy SK, et al. Paternal nicotine exposure in rats produces long-lasting neurobehavioral effects in the offspring. Neurotoxicol Teratol. 2019;74:106808. Epub 2019/05/20. doi: 10.1016/j.ntt.2019.05.001 31103693.
27. Pachenari N, Azizi H, Semnaniann S. Adolescent Morphine Exposure in Male Rats Alters the Electrophysiological Properties of Locus Coeruleus Neurons of the Male Offspring. Neuroscience. 2019;410:108–17. Epub 2019/05/16. doi: 10.1016/j.neuroscience.2019.05.009 31085281.
28. Levin ED, Hawkey AB, Hall BJ, Cauley M, Slade S, Yazdani E, et al. Paternal THC exposure in rats causes long-lasting neurobehavioral effects in the offspring. Neurotoxicol Teratol. 2019;74:106806. Epub 2019/04/28. doi: 10.1016/j.ntt.2019.04.003 31028824.
29. Jung YH, Sauria MEG, Lyu X, Cheema MS, Ausio J, Taylor J, et al. Chromatin States in Mouse Sperm Correlate with Embryonic and Adult Regulatory Landscapes. Cell Rep. 2017;18(6):1366–82. Epub 2017/02/09. doi: 10.1016/j.celrep.2017.01.034 28178516; PubMed Central PMCID: PMC5313040.
30. Holland ML, Lowe R, Caton PW, Gemma C, Carbajosa G, Danson AF, et al. Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice. Science. 2016;353(6298):495–8. Epub 2016/07/09. doi: 10.1126/science.aaf7040 27386920; PubMed Central PMCID: PMC5734613.
31. Brieno-Enriquez MA, Garcia-Lopez J, Cardenas DB, Guibert S, Cleroux E, Ded L, et al. Exposure to endocrine disruptor induces transgenerational epigenetic deregulation of microRNAs in primordial germ cells. PLoS One. 2015;10(4):e0124296. Epub 2015/04/22. doi: 10.1371/journal.pone.0124296 25897752; PubMed Central PMCID: PMC4405367.
32. Venugopal R, Jaiswal AK. Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes. Oncogene. 1998;17(24):3145–56. doi: 10.1038/sj.onc.1202237 9872330.
33. Ishii T, Itoh K, Takahashi S, Sato H, Yanagawa T, Katoh Y, et al. Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. J Biol Chem. 2000;275(21):16023–9. Epub 2000/05/24. doi: 10.1074/jbc.275.21.16023 10821856.
34. Tsaprouni LG, Yang TP, Bell J, Dick KJ, Kanoni S, Nisbet J, et al. Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation. Epigenetics. 2014;9(10):1382–96. Epub 2014/11/27. doi: 10.4161/15592294.2014.969637 25424692; PubMed Central PMCID: PMC4623553.
35. Zeilinger S, Kuhnel B, Klopp N, Baurecht H, Kleinschmidt A, Gieger C, et al. Tobacco smoking leads to extensive genome-wide changes in DNA methylation. PLoS One. 2013;8(5):e63812. Epub 2013/05/22. doi: 10.1371/journal.pone.0063812 23691101; PubMed Central PMCID: PMC3656907.
36. Whitelaw NC, Chong S, Morgan DK, Nestor C, Bruxner TJ, Ashe A, et al. Reduced levels of two modifiers of epigenetic gene silencing, Dnmt3a and Trim28, cause increased phenotypic noise. Genome Biol. 2010;11(11):R111. Epub 2010/11/26. doi: 10.1186/gb-2010-11-11-r111 21092094; PubMed Central PMCID: PMC3156950.
37. Dalgaard K, Landgraf K, Heyne S, Lempradl A, Longinotto J, Gossens K, et al. Trim28 Haploinsufficiency Triggers Bi-stable Epigenetic Obesity. Cell. 2016;164(3):353–64. Epub 2016/01/30. doi: 10.1016/j.cell.2015.12.025 26824653; PubMed Central PMCID: PMC4735019.
38. Radford EJ, Ito M, Shi H, Corish JA, Yamazawa K, Isganaitis E, et al. In utero effects. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism. Science. 2014;345(6198):1255903. Epub 2014/07/12. doi: 10.1126/science.1255903 25011554; PubMed Central PMCID: PMC4404520.
39. Iqbal K, Tran DA, Li AX, Warden C, Bai AY, Singh P, et al. Deleterious effects of endocrine disruptors are corrected in the mammalian germline by epigenome reprogramming. Genome Biol. 2015;16:59. Epub 2015/04/09. doi: 10.1186/s13059-015-0619-z 25853433; PubMed Central PMCID: PMC4376074.
40. Chen Q, Yan M, Cao Z, Li X, Zhang Y, Shi J, et al. Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science. 2016;351(6271):397–400. Epub 2016/01/02. doi: 10.1126/science.aad7977 26721680.
41. Shi J, Zhang Y, Zhou T, Chen Q. tsRNAs: The Swiss Army Knife for Translational Regulation. Trends Biochem Sci. 2019;44(3):185–9. Epub 2018/10/10. doi: 10.1016/j.tibs.2018.09.007 30297206; PubMed Central PMCID: PMC6379142.
42. Sharma U, Conine CC, Shea JM, Boskovic A, Derr AG, Bing XY, et al. Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science. 2016;351(6271):391–6. Epub 2016/01/02. doi: 10.1126/science.aad6780 26721685; PubMed Central PMCID: PMC4888079.
43. Zhang Y, Zhang X, Shi J, Tuorto F, Li X, Liu Y, et al. Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs. Nat Cell Biol. 2018;20(5):535–40. Epub 2018/04/27. doi: 10.1038/s41556-018-0087-2 29695786; PubMed Central PMCID: PMC5926820.
44. Thompson DM, Lu C, Green PJ, Parker R. tRNA cleavage is a conserved response to oxidative stress in eukaryotes. RNA. 2008;14(10):2095–103. Epub 2008/08/23. doi: 10.1261/rna.1232808 18719243; PubMed Central PMCID: PMC2553748.
45. Natt D, Kugelberg U, Casas E, Nedstrand E, Zalavary S, Henriksson P, et al. Human sperm displays rapid responses to diet. PLoS Biol. 2019;17(12):e3000559. Epub 2019/12/27. doi: 10.1371/journal.pbio.3000559 31877125; PubMed Central PMCID: PMC6932762.
46. Zhang Y, Chen Q. Human sperm RNA code senses dietary sugar. Nat Rev Endocrinol. 2020;16(4):200–1. Epub 2020/02/19. doi: 10.1038/s41574-020-0331-2 32066893; PubMed Central PMCID: PMC7080589.
47. Mashoodh R, Habrylo IB, Gudsnuk KM, Pelle G, Champagne FA. Maternal modulation of paternal effects on offspring development. Proc Biol Sci. 2018;285(1874). Epub 2018/03/09. doi: 10.1098/rspb.2018.0118 29514964; PubMed Central PMCID: PMC5879637.
48. Cavalli G, Heard E. Advances in epigenetics link genetics to the environment and disease. Nature. 2019;571(7766):489–99. Epub 2019/07/26. doi: 10.1038/s41586-019-1411-0 31341302.
49. Heard E, Martienssen RA. Transgenerational epigenetic inheritance: myths and mechanisms. Cell. 2014;157(1):95–109. Epub 2014/04/01. doi: 10.1016/j.cell.2014.02.045 24679529; PubMed Central PMCID: PMC4020004.
50. Horsthemke B. A critical view on transgenerational epigenetic inheritance in humans. Nat Commun. 2018;9(1):2973. Epub 2018/08/01. doi: 10.1038/s41467-018-05445-5 30061690; PubMed Central PMCID: PMC6065375.
51. Vallaster MP, Kukreja S, Bing XY, Ngolab J, Zhao-Shea R, Gardner PD, et al. Paternal nicotine exposure alters hepatic xenobiotic metabolism in offspring. Elife. 2017;6. Epub 2017/02/15. doi: 10.7554/eLife.24771 28196335; PubMed Central PMCID: PMC5340528.
52. Zhang W, Yang J, Lv Y, Li S, Qiang M. Paternal benzo[a]pyrene exposure alters the sperm DNA methylation levels of imprinting genes in F0 generation mice and their unexposed F1-2 male offspring. Chemosphere. 2019;228:586–94. Epub 2019/05/07. doi: 10.1016/j.chemosphere.2019.04.092 31059956.
53. Viluksela M, Pohjanvirta R. Multigenerational and Transgenerational Effects of Dioxins. Int J Mol Sci. 2019;20(12). Epub 2019/06/20. doi: 10.3390/ijms20122947 31212893.
54. McCarthy DM, Morgan TJ Jr., Lowe SE, Williamson MJ, Spencer TJ, Biederman J, et al. Nicotine exposure of male mice produces behavioral impairment in multiple generations of descendants. PLoS Biol. 2018;16(10):e2006497. Epub 2018/10/17. doi: 10.1371/journal.pbio.2006497 30325916.
55. Barrett EG, Wilder JA, March TH, Espindola T, Bice DE. Cigarette smoke-induced airway hyperresponsiveness is not dependent on elevated immunoglobulin and eosinophilic inflammation in a mouse model of allergic airway disease. Am J Respir Crit Care Med. 2002;165(10):1410–8. doi: 10.1164/rccm.2106029 12016105.
56. Chiu K, Lau WM, Lau HT, So KF, Chang RC. Micro-dissection of rat brain for RNA or protein extraction from specific brain region. J Vis Exp. 2007;(7):269. doi: 10.3791/269 18989440; PubMed Central PMCID: PMC2565859.
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