{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:42:54Z","timestamp":1788414174607,"version":"build-2803163510"},"reference-count":150,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001824","name":"Czech Science Foundation","doi-asserted-by":"publisher","award":["20-16633S"],"award-info":[{"award-number":["20-16633S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>In recent years, we have seen an increasing amount of evidence pointing to the existence of a non-genetic heredity of the effects of events such as separation from parents, threat to life, or other traumatising experiences such as famine. This heredity is often mediated by epigenetic regulations of gene expression and may be transferred even across several generations. In this review, we focus on studies which involve transgenerational epigenetic inheritance (TEI), with a short detour to intergenerational studies focused on the inheritance of trauma or stressful experiences. The reviewed studies show a plethora of universal changes which stress exposure initiates on multiple levels of organisation ranging from hormonal production and the hypothalamic-pituitary-adrenal (HPA) axis modulation all the way to cognition, behaviour, or propensity to certain psychiatric or metabolic disorders. This review will also provide an overview of relevant methodology and difficulties linked to implementation of epigenetic studies. A better understanding of these processes may help us elucidate the evolutionary pathways which are at work in the course of emergence of the diseases and disorders associated with exposure to trauma, either direct or in a previous generation.<\/jats:p>","DOI":"10.3390\/genes14010120","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T02:12:48Z","timestamp":1672625568000},"page":"120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Transgenerational Epigenetic Inheritance of Traumatic Experience in Mammals"],"prefix":"10.3390","volume":"14","author":[{"given":"Jana","family":"\u0160vorcov\u00e1","sequence":"first","affiliation":[{"name":"Department of Philosophy and History of Science, Faculty of Science, Charles University, 128 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.tig.2022.03.010","article-title":"DNA methylation: A historical perspective","volume":"38","author":"Mattei","year":"2022","journal-title":"Trends Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/ije\/dyr184","article-title":"The Epigenotype. 1942","volume":"41","author":"Waddington","year":"2012","journal-title":"Int. J. Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1387\/ijdb.052049sn","article-title":"Before programs: The physical origination of multicellular forms","volume":"50","author":"Newman","year":"2006","journal-title":"Int. J. Dev. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev.ge.07.120173.001021","article-title":"Paramutation","volume":"7","author":"Brink","year":"1973","journal-title":"Annu. Rev. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Jablonka, E., and Lamb, M. (1995). Epigenetic Inheritance and Evolution: The Lamarckian Dimension, Oxford University Press.","DOI":"10.1093\/oso\/9780198540625.001.0001"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Marko\u0161, A., and \u0160vorcov\u00e1, J. (2019). Epigenetic Processes and the Evolution of Life, CRC Press.","DOI":"10.1201\/9781351009966"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.tplants.2012.01.001","article-title":"Epigenetic and epigenomic variation in Arabidopsis thaliana","volume":"17","author":"Schmitz","year":"2012","journal-title":"Trends Plant Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1111\/j.1469-8137.2009.03121.x","article-title":"Stress-induced DNA methylation changes and their heritability in asexual dandelions","volume":"185","author":"Verhoeven","year":"2010","journal-title":"New Phytol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/43657","article-title":"An epigenetic mutation responsible for natural variation in floral symmetry","volume":"401","author":"Cubas","year":"1999","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/s41586-018-0239-3","article-title":"Epigenetic inheritance mediated by coupling of RNAi and histone H3K9 methylation","volume":"558","author":"Yu","year":"2018","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.cell.2011.05.029","article-title":"Inheritance of stress-induced, ATF-2-dependent epigenetic change","volume":"145","author":"Seong","year":"2011","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1101\/gad.269503","article-title":"Inheritance of polycomb-dependent chromosomal interactions in Drosophila","volume":"17","author":"Bantignies","year":"2003","journal-title":"Genes Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/nature10572","article-title":"Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans","volume":"479","author":"Greer","year":"2011","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.cell.2014.06.020","article-title":"Starvation-Induced Transgenerational Inheritance of Small RNAs in C. elegans","volume":"158","author":"Rechavi","year":"2014","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.celrep.2014.02.044","article-title":"A histone methylation network regulates transgenerational epigenetic memory in C. elegans","volume":"7","author":"Greer","year":"2014","journal-title":"Cell Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e54309","DOI":"10.7554\/eLife.54309","article-title":"Caenorhabditis elegans nuclear RNAi factor SET-32 deposits the transgenerational histone modification, H3K23me3","volume":"9","author":"Zhang","year":"2020","journal-title":"Elife"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/15490","article-title":"Epigenetic inheritance at the agouti locus in the mouse","volume":"23","author":"Morgan","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5293","DOI":"10.1128\/MCB.23.15.5293-5300.2003","article-title":"Transposable Elements: Targets for Early Nutritional Effects on Epigenetic Gene Regulation","volume":"23","author":"Waterland","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"17308","DOI":"10.1073\/pnas.0607090103","article-title":"Germ-line epigenetic modification of the murine Avy allele by nutritional supplementation","volume":"103","author":"Cropley","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Blewitt, M., Vickaryous, N.K., Paldi, A., Koseki, H., and Whitelaw, E. (2006). Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in mice. PLoS Genet., 2.","DOI":"10.1371\/journal.pgen.0020049"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1093\/genetics\/88.3.529","article-title":"Influence of maternal phenotype on metabolic differentiation of agouti locus mutants in the mouse","volume":"88","author":"Wolff","year":"1978","journal-title":"Genetics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1046\/j.1365-2540.2001.00868.x","article-title":"Alternative splicing and expressivity of the Axin(Fu) allele in mice","volume":"87","author":"Flood","year":"2001","journal-title":"Heredity"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/dvg.20230","article-title":"Maternal Methyl Supplements Increase Offspring DNA methylation at Axin Fused","volume":"44","author":"Waterland","year":"2006","journal-title":"Genesis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.semcdb.2019.08.002","article-title":"Metastable epialleles and their contribution to epigenetic inheritance in mammals","volume":"97","author":"Bertozzi","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1002\/ece3.1993","article-title":"Paternal heat exposure causes DNA methylation and gene expression changes of Stat3 in Wild guinea pig sons","volume":"6","author":"Weyrich","year":"2016","journal-title":"Ecol. Evol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e22406","DOI":"10.1096\/fj.202101948R","article-title":"Embryonic heat conditioning in chicks induces transgenerational heat\/immunological resilience via methylation on regulatory elements","volume":"36","author":"Rosenberg","year":"2022","journal-title":"FASEB J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1093\/jn\/135.6.1382","article-title":"Dietary Protein Restriction of Pregnant Rats Induces and Folic Acid Supplementation Prevents Epigenetic Modification of Hepatic Gene Expression in the Offspring","volume":"135","author":"Lillycrop","year":"2005","journal-title":"J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1210\/en.2010-1461","article-title":"Maternal high-fat diet effects on third-generation female body size via the paternal lineage","volume":"152","author":"Dunn","year":"2011","journal-title":"Endocrinology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1093\/jn\/136.6.1522","article-title":"A Folate- and Methyl-Deficient Diet Alters the Expression of DNA Methyltransferases and Methyl CpG Binding Proteins Involved in Epigenetic Gene Silencing in Livers of F344 Rats1","volume":"136","author":"Ghoshal","year":"2006","journal-title":"J. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/sj.ejhg.5201538","article-title":"Sex-specific, male-line transgenerational responses in humans","volume":"14","author":"Pembrey","year":"2006","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1177\/0269881113503504","article-title":"Female adolescent exposure to cannabinoids causes transgenerational effects on morphine sensitization in female offspring in the absence of in utero exposure","volume":"27","author":"Vassoler","year":"2013","journal-title":"J. Psychopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gangisetty, O., Chaudhary, S., Palagani, A., and Sarkar, D.K. (2022). Transgenerational inheritance of fetal alcohol effects on proopiomelanocortin gene expression and methylation, cortisol response to stress, and anxiety-like behaviors in offspring for three generations in rats: Evidence for male germline transmission. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0263340"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.reprotox.2004.05.008","article-title":"Effect of the anti-androgenic endocrine disruptor vinclozolin on embryonic testis cord formation and postnatal testis development and function","volume":"18","author":"Uzumcu","year":"2004","journal-title":"Reprod. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1126\/science.1108190","article-title":"Toxicology: Epigenetic transgenerational actions of endocrine disruptors and male fertility","volume":"308","author":"Anway","year":"2005","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5515","DOI":"10.1210\/en.2006-0640","article-title":"Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease","volume":"147","author":"Anway","year":"2006","journal-title":"Endocrinology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5942","DOI":"10.1073\/pnas.0610410104","article-title":"Transgenerational epigenetic imprints on mate preference","volume":"104","author":"Crews","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"dvw001","DOI":"10.1093\/eep\/dvw001","article-title":"Ancestral vinclozolin exposure alters the epigenetic transgenerational inheritance of sperm small noncoding RNAs","volume":"2","author":"Schuster","year":"2016","journal-title":"Environ. Epigenetics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13059-015-0619-z","article-title":"Deleterious effects of endocrine disruptors are corrected in the mammalian germline by epigenome reprogramming","volume":"16","author":"Iqbal","year":"2015","journal-title":"Genome Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.lfs.2009.10.004","article-title":"Perinatal exposure of rats to Bisphenol A affects the fertility of male offspring","volume":"85","author":"Salian","year":"2009","journal-title":"Life Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.reprotox.2010.10.003","article-title":"Developmental exposure to TCDD reduces fertility and negatively affects pregnancy outcomes across multiple generations","volume":"31","author":"Osteen","year":"2011","journal-title":"Reprod. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Nilsson, E., Larsen, G., Manikkam, M., Guerrero-Bosagna, C., Savenkova, M.I., and Skinner, M.K. (2012). Environmentally induced epigenetic transgenerational inheritance of ovarian disease. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036129"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"977416","DOI":"10.3389\/fnbeh.2022.977416","article-title":"Prenatal maternal stress and offspring aggressive behavior: Intergenerational and transgenerational inheritance","volume":"16","author":"Mbiydzenyuy","year":"2022","journal-title":"Front. Behav. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/s41576-021-00438-5","article-title":"Molecular mechanisms of transgenerational epigenetic inheritance","volume":"23","author":"Cavalli","year":"2022","journal-title":"Nat. Rev. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1002\/bies.201500076","article-title":"N6-methyladenine functions as a potential epigenetic mark in eukaryotes","volume":"37","author":"Sun","year":"2015","journal-title":"Bioessays"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.freeradbiomed.2016.11.038","article-title":"Oxidized C5-methyl cytosine bases in DNA: 5-Hydroxymethylcytosine; 5-formylcytosine; and 5-carboxycytosine","volume":"107","author":"Klungland","year":"2017","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_46","first-page":"56","article-title":"The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus","volume":"354","author":"Barlow","year":"1991","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3804","DOI":"10.1038\/s41467-021-23510-4","article-title":"Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3","volume":"12","author":"Santini","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1097\/MOP.0000000000000965","article-title":"Imprinting disorders in humans: A review","volume":"32","author":"Butler","year":"2020","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.1063443","article-title":"Epigenetic reprogramming in mammalian development","volume":"293","author":"Reik","year":"2001","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1093\/bfgp\/els042","article-title":"Restoring totipotency through epigenetic reprogramming","volume":"12","author":"Wasson","year":"2013","journal-title":"Brief. Funct. Genom."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.cell.2019.01.043","article-title":"Genomic Imprinting and Physiological Processes in Mammals","volume":"176","author":"Tucci","year":"2019","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/gene.10168","article-title":"Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse","volume":"35","author":"Lane","year":"2003","journal-title":"Genesis"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1126\/science.1229277","article-title":"Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine","volume":"339","author":"Hackett","year":"2013","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.molcel.2012.11.001","article-title":"The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells","volume":"48","author":"Seisenberger","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13059-020-02036-w","article-title":"Protection from DNA re-methylation by transcription factors in primordial germ cells and pre-implantation embryos can explain trans-generational epigenetic inheritance","volume":"21","author":"Kremsky","year":"2020","journal-title":"Genome Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature11093","article-title":"PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos","volume":"486","author":"Nakamura","year":"2012","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin modifications and their function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12943-021-01373-z","article-title":"Histone citrullination: A new target for tumors","volume":"20","author":"Zhu","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.molcel.2019.04.025","article-title":"Where, When, and How: Context-Dependent Functions of RNA Methylation Writers, Readers, and Erasers","volume":"74","author":"Shi","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1126\/science.1255023","article-title":"H3K27me and PRC2 transmit a memory of repression across generations and during development","volume":"345","author":"Gaydos","year":"2014","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nature08162","article-title":"Distinctive chromatin in human sperm packages genes for embryo development","volume":"460","author":"Hammoud","year":"2009","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1756-8935-7-2","article-title":"Epigenetic marking of sperm by post-translational modification of histones and protamines","volume":"7","author":"Brunner","year":"2014","journal-title":"Epigenetics Chromatin"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"eabh0556","DOI":"10.1126\/science.abh0556","article-title":"Nurse cell \u2013derived small RNAs define paternal epigenetic inheritance in Arabidopsis","volume":"373","author":"Long","year":"2021","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1038\/cr.2012.141","article-title":"A novel class of tRNA-derived small RNAs extremely enriched in mature mouse sperm","volume":"22","author":"Peng","year":"2012","journal-title":"Cell Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.semcdb.2019.07.005","article-title":"Sperm RNA: Quo vadis?","volume":"97","author":"Bohacek","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_66","first-page":"1","article-title":"Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals","volume":"6780","author":"Sharma","year":"2015","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/nature04674","article-title":"RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse","volume":"441","author":"Rassoulzadegan","year":"2006","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"18193","DOI":"10.1038\/srep18193","article-title":"RNA-mediated paternal heredity of diet-induced obesity and metabolic disorders","volume":"5","author":"Grandjean","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1126\/science.aad7977","article-title":"Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder","volume":"351","author":"Chen","year":"2016","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10547","DOI":"10.1073\/pnas.1820810116","article-title":"Maternal overnutrition programs hedonic and metabolic phenotypes across generations through sperm tsRNAs","volume":"116","author":"Sarker","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/s41574-019-0226-2","article-title":"Sperm RNA code programmes the metabolic health of offspring","volume":"15","author":"Zhang","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e12407","DOI":"10.1111\/gbb.12407","article-title":"Epigenetic germline inheritance in mammals: Looking to the past to understand the future","volume":"17","author":"Gapp","year":"2017","journal-title":"Genes Brain Behav."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Cossetti, C., Lugini, L., Astrologo, L., Saggio, I., Fais, S., and Spadafora, C. (2014). Soma-to-germline transmission of RNA in mice xenografted with human tumour cells: Possible transport by exosomes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101629"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.devcel.2018.06.023","article-title":"Small RNAs Are Trafficked from the Epididymis to Developing Mammalian Sperm","volume":"46","author":"Sharma","year":"2018","journal-title":"Dev. Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.pbiomolbio.2012.12.003","article-title":"Transgenerational epigenetic inheritance: Focus on soma to germline information transfer","volume":"113","author":"Sharma","year":"2013","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Chan, J.C., Nugent, B.M., Morrison, K.E., Ja\u0161arevi\u0107, E., Bhanu, N.V., Garcia, B.A., and Bale, T.L. (bioRxiv, 2018). Epididymal glucocorticoid receptors promote intergenerational transmission of paternal stress, bioRxiv, preprint.","DOI":"10.1101\/321976"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/nrg1616","article-title":"Prions as adaptive conduits of memory and inheritance","volume":"6","author":"Shorter","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1126\/science.1191078","article-title":"Molecular signals of epigenetic states","volume":"330","author":"Bonasio","year":"2010","journal-title":"Science"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1086\/598822","article-title":"Transgenerational epigenetic inheritance: Prevalence, mechanisms, and implications for the study of heredity and evolution","volume":"84","author":"Jablonka","year":"2009","journal-title":"Q. Rev. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nmeth.4181","article-title":"A guide to designing germline-dependent epigenetic inheritance experiments in mammals","volume":"14","author":"Bohacek","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.pbiomolbio.2012.08.014","article-title":"Epigenetic inheritance and plasticity: The responsive germline","volume":"111","author":"Jablonka","year":"2013","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_82","first-page":"1088","article-title":"Elevated Plus Maze for Mice","volume":"22","author":"Komada","year":"2008","journal-title":"J. Vis. Exp."},{"key":"ref_83","first-page":"3638","article-title":"The mouse forced swim test","volume":"59","author":"Can","year":"2012","journal-title":"J. Vis. Exp."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/S0959-4388(99)80016-6","article-title":"Maternal care and the development of stress responses","volume":"9","author":"Francis","year":"1999","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0031-9384(03)00149-5","article-title":"Variations in maternal care in the rat as a mediating influence for the effects of environment on development","volume":"79","author":"Champagne","year":"2003","journal-title":"Physiol. Behav."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/nn1276","article-title":"Epi-genetic programming by maternal behavior","volume":"7","author":"Weaver","year":"2004","journal-title":"Nat. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.3389\/fimmu.2019.01545","article-title":"A general introduction to glucocorticoid biology","volume":"10","author":"Timmermans","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.yhbeh.2014.03.005","article-title":"Transgenerational effects of social stress on social behavior, corticosterone, oxytocin, and prolactin in rats","volume":"65","author":"Babb","year":"2014","journal-title":"Horm. Behav."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/nn.2270","article-title":"Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse","volume":"12","author":"McGowan","year":"2009","journal-title":"Nat. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.neuroscience.2016.05.046","article-title":"Altered brain morphology and functional connectivity reflect a vulnerable affective state after cumulative multigenerational stress in rats","volume":"330","author":"McCreary","year":"2016","journal-title":"Neuroscience"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/mp.2014.80","article-title":"Pathological brain plasticity and cognition in the offspring of males subjected to postnatal traumatic stress","volume":"20","author":"Bohacek","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.biopsych.2012.01.034","article-title":"Differential glucocorticoid receptor exon 1 B, 1 C, and 1 H expression and methylation in suicide completers with a history of childhood abuse","volume":"72","author":"Labonte","year":"2012","journal-title":"Biol. Psychiatry"},{"key":"ref_93","first-page":"249","article-title":"Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Sexually abused Girls","volume":"78","author":"Chrousos","year":"1994","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1176\/appi.ajp.159.12.2072","article-title":"Childhood Trauma Associated With Smaller Hippocampal Volume in Women With Major Depression","volume":"159","author":"Vythilingam","year":"2002","journal-title":"Am. J. Psychiatry"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"97","DOI":"10.4161\/epi.3.2.6034","article-title":"Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses","volume":"3","author":"Oberlander","year":"2008","journal-title":"Epigenetics"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e12638","DOI":"10.1111\/gbb.12638","article-title":"Proximate causes and consequences of intergenerational influences of salient sensory experience","volume":"19","author":"Aoued","year":"2020","journal-title":"Genes Brain Behav."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1038\/s41380-018-0271-6","article-title":"Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma","volume":"25","author":"Gapp","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1136\/heart.84.6.595","article-title":"Coronary heart disease after prenatal exposure to the Dutch famine, 1944\u201345","volume":"84","author":"Roseboom","year":"2000","journal-title":"Heart"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1093\/ajcn\/84.2.322","article-title":"Early onset of coronary artery disease after prenatal exposure to the Dutch famine1\u20133","volume":"84","author":"Painter","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1176\/ajp.153.12.1637","article-title":"Schizoid Personality Disorder After Prenatal Exposure to Famine","volume":"153","author":"Hoek","year":"1996","journal-title":"Am. J. Psychiatry"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1111\/j.1471-0528.2008.01822.x","article-title":"Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life","volume":"115","author":"Painter","year":"2008","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1111\/1471-0528.12136","article-title":"Transgenerational effects of prenatal exposure to the 1944\u201345 Dutch famine","volume":"120","author":"Veenendaal","year":"2013","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1097\/HJH.0000000000000640","article-title":"Seventy years after the siege of Leningrad: Does early life famine still affect cardiovascular risk and aging?","volume":"33","author":"Rotar","year":"2015","journal-title":"J. Hypertens."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1146\/annurev-publhealth-031210-101230","article-title":"Prenatal famine and adult health","volume":"32","author":"Lumey","year":"2011","journal-title":"Annu. Rev. Public Health"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ehb.2016.07.001","article-title":"Transgenerational effects of childhood conditions on third generation health and education outcomes","volume":"23","author":"Pinger","year":"2016","journal-title":"Econ. Hum. Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1037\/tra0000302","article-title":"Trauma across generations and paths to adaptation and resilience","volume":"10","author":"Lehrner","year":"2018","journal-title":"Psychol. Trauma Theory Res. Pract. Policy"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1176\/ajp.155.9.1163","article-title":"Vulnerability to posttraumatic stress disorder in adult offspring of Holocaust survivors","volume":"155","author":"Yehuda","year":"1998","journal-title":"Am. J. Psychiatry"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1155\/2011\/185354","article-title":"The role of genes in defining a molecular biology of PTSD","volume":"30","author":"Yehuda","year":"2011","journal-title":"Dis. Markers"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.psyneuen.2013.11.019","article-title":"Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors","volume":"40","author":"Lehrner","year":"2014","journal-title":"Psychoneuroendocrinology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/cdev.12487","article-title":"Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic\u2013Pituitary\u2013Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo","volume":"87","author":"Kertes","year":"2016","journal-title":"Child Dev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.biopsych.2015.08.005","article-title":"Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation","volume":"80","author":"Yehuda","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"ref_112","unstructured":"Rowland-Klein, D., and Dunlop, R. (2013). The Transmission of Trauma across Generations: Identification with Parental Trauma in Children of Holocaust Survivors. Handbook of Stress, Trauma, and the Family, Routledge\/Taylor & Francis Group."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1023\/A:1025706427300","article-title":"Are Children of Holocaust Survivors Less Well-Adapted? A Meta-Analytic Investigation of Secondary Traumatization","volume":"16","year":"2003","journal-title":"J. Trauma. Stress"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5466","DOI":"10.1038\/ncomms6466","article-title":"Early life stress in fathers improves behavioural flexibility in their offspring","volume":"5","author":"Gapp","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_115","first-page":"144","article-title":"Psychopathology and other health dimensions among the offspring of Holocaust survivors: Results from the Israel National Health Survey","volume":"44","author":"Levav","year":"2007","journal-title":"Isr. J. Psychiatry Relat. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1080\/14616730802113661","article-title":"Does intergenerational transmission of trauma skip a generation? No meta-analytic evidence for tertiary traumatization with third generation of Holocaust survivors","volume":"10","year":"2008","journal-title":"Attach. Hum. Dev."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nn.3594","article-title":"Parental olfactory experience influences behavior and neural structure in subsequent generations","volume":"17","author":"Dias","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"12846","DOI":"10.1073\/pnas.1505068112","article-title":"Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size","volume":"112","author":"Morrison","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.biopsych.2018.07.028","article-title":"Reversing Behavioral, Neuroanatomical, and Germline Influences of Intergenerational Stress","volume":"85","author":"Aoued","year":"2019","journal-title":"Biol. Psychiatry"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.celrep.2018.03.059","article-title":"RNA-Dependent Intergenerational Inheritance of Enhanced Synaptic Plasticity after Environmental Enrichment","volume":"23","author":"Benito","year":"2018","journal-title":"Cell Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nn.3695","article-title":"Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice","volume":"17","author":"Gapp","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"13699","DOI":"10.1073\/pnas.1508347112","article-title":"Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress","volume":"112","author":"Rodgers","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Jawaid, A., Kunzi, M., Mansoor, M., Khan, Z.Y., Abid, A., Taha, M., Rigotti, S., Thumfart, K., Faisal, S., and Chughtai, O. (medRxiv, 2020). Distinct microRNA signature in human serum and germline after childhood trauma, medRxiv, preprint.","DOI":"10.1101\/2020.08.11.20168393"},{"key":"ref_124","first-page":"dvy023","article-title":"Transgenerational inheritance of behavioral and metabolic effects of paternal exposure to traumatic stress in early postnatal life: Evidence in the 4th generation","volume":"4","author":"Roszkowski","year":"2018","journal-title":"Environ. Epigenetics"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"7101","DOI":"10.1073\/pnas.1305399110","article-title":"Epigenetics: Core misconcept","volume":"110","author":"Ptashne","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.cell.2014.02.045","article-title":"Transgenerational epigenetic inheritance: Myths and mechanisms","volume":"157","author":"Heard","year":"2014","journal-title":"Cell"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1038\/s41467-018-05445-5","article-title":"A critical view on transgenerational epigenetic inheritance in humans","volume":"9","author":"Horsthemke","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nrg3435","article-title":"Transgenerational epigenetic inheritance: How important is it?","volume":"14","author":"Grossniklaus","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1096\/fj.201500083","article-title":"Transgenerational epigenetic inheritance in mammals: How good is the evidence?","volume":"30","author":"Michels","year":"2016","journal-title":"FASEB J."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1126\/science.343.6169.361","article-title":"The Epigenetics Heretic","volume":"343","author":"Kaiser","year":"2014","journal-title":"Science"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41467-017-02306-5","article-title":"APRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients","volume":"9","author":"Oussalah","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/ng1157","article-title":"Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease","volume":"34","author":"Tufarelli","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_133","unstructured":"Mitchell, K. (2022, November 10). Calibrating Scientific Skepticism\u2014A Wider Look at the Field of Transgenerational Epigenetics. 2018. Blog Entry. Available online: http:\/\/www.wiringthebrain.com\/2018\/07\/calibrating-scientific-skepticism-wider.html."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"20150682","DOI":"10.1098\/rspb.2015.0682","article-title":"When is incomplete epigenetic resetting in germ cells favoured by natural selection?","volume":"282","author":"Uller","year":"2015","journal-title":"Proc. R. Soc. B Boil. Sci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/jtbi.1996.0109","article-title":"The inheritance of phenotypes: An adaptation to fluctuating environments","volume":"181","author":"Lachmann","year":"1996","journal-title":"J. Theor. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"4226","DOI":"10.1096\/fj.12-224048","article-title":"Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content","volume":"27","author":"Fullston","year":"2013","journal-title":"FASEB J."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Fullston, T., Ohlsson-Teague, E.M.C., Print, C.G., Sandeman, L.Y., and Lane, M. (2016). Sperm microRNA content is altered in a mouse model of male obesity, but the same suite of microRNAs are not altered in offspring\u2019s sperm. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166076"},{"key":"ref_138","unstructured":"Portin, P. (2012). Does epigenetic inheritance revolutionize the foundations of the theory of evolution?. Curr. Top. Genet., 5, Available online: http:\/\/www.researchtrends.net\/tia\/article_pdf.asp?in=0&vn=5&tid=45&aid=3652."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"20151019","DOI":"10.1098\/rspb.2015.1019","article-title":"The extended evolutionary synthesis: Its structure, assumptions and predictions","volume":"282","author":"Laland","year":"2015","journal-title":"Proc. R. Soc. B Boil. Sci."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"West-Eberhard, M.J. (2003). Developmental Plasticity and Evolution, Oxford University Press.","DOI":"10.1093\/oso\/9780195122343.003.0008"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1086\/276408","article-title":"A New Factor in Evolution Published by: The University of Chicago Press for the American Society of Naturalists Stable","volume":"30","author":"Baldwin","year":"1896","journal-title":"Am. Nat."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"118","DOI":"10.2307\/2405747","article-title":"Genetic Assimilation of an Acquired Character","volume":"7","author":"Waddington","year":"1952","journal-title":"Evolution"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2307\/2406091","article-title":"Genetic Assimilation of the Bithorax Phenotype","volume":"10","author":"Waddington","year":"1956","journal-title":"Evolution"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.1098\/rstb.2009.0125","article-title":"Epigenetic responses to environmental change and their evolutionary implications","volume":"364","author":"Turner","year":"2009","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"8204","DOI":"10.1093\/nar\/gkv693","article-title":"The interplay between DNA methylation and sequence divergence in recent human evolution","volume":"43","author":"Heyn","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrg3890","article-title":"The effects of chromatin organization on variation in mutation rates in the genome","volume":"16","author":"Makova","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"908","DOI":"10.3389\/fpsyg.2014.00908","article-title":"Extended evolutionary psychology: The importance of transgenerational developmental plasticity","volume":"5","author":"Stotz","year":"2014","journal-title":"Front. Psychol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1126\/science.aam6142","article-title":"Epigenetics and the evolution of instincts: Instincts may evolve from learning and share the same cellular and molecular mechanisms","volume":"356","author":"Robinson","year":"2017","journal-title":"Science"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"642220","DOI":"10.3389\/fgene.2021.642220","article-title":"Epigenetics as Driver of Adaptation and Diversification in Microbial Eukaryotes","volume":"12","author":"Weiner","year":"2021","journal-title":"Front. Genet."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"14139","DOI":"10.1038\/s41598-017-14673-6","article-title":"Epigenetics and adaptive phenotypic variation between habitats in an asexual snail","volume":"7","author":"Thorson","year":"2017","journal-title":"Sci. Rep."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/1\/120\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:55:37Z","timestamp":1760118937000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/1\/120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,1]]},"references-count":150,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["genes14010120"],"URL":"https:\/\/doi.org\/10.3390\/genes14010120","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,1]]}}}