Abstract
If genetics defines the inheritance of DNA, epigenetics aims to regulate and make it adaptable. Epigenetic alterations include DNA methylation, chromatin remodelling, post-translational modifications of histone proteins and activity of non-coding RNAs. Several studies, especially in animal models, have reported transgenerational inheritance of epigenetic marks. However, evidence of transgenerational inheritance in humans via germline in the absence of any direct exposure to the driving external stimulus remains controversial. Most of the epimutations exist in relation with genetic variants. The present review looks at intergenerational and transgenerational inheritance in humans, (both father and mother) in response to diet, exposure to chemicals, stress, exercise, and disease status. If not transgenerational, at least intergenerational human studies could help to understand early processes of inheritance. In humans, female and male germline development follow separate paths of epigenetic events and both oocyte and sperm possess their own unique epigenomes. While DNA methylation alterations are reset during epigenetic reprogramming, non-coding RNAs via human sperm provide evidence of being reliable carriers for transgenerational inheritance. Human studies reveal that one mechanism of epigenetic inheritance cannot be applied to the complete human genome. Multiple factors including time, type, and tissue of exposure determine if the modified epigenetic mark could be transmissible and till which generation. Population-specific differences should also be taken into consideration while associating inheritance to an environmental exposure. A longitudinal study targeting one environmental factor, but different population groups should be conducted at a specific geographical location to pinpoint heritable epigenetic changes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adrian-Kalchhauser I, Sultan SE, Shama LNS, Spence-Jones H, Tiso S, Keller Valsecchi CI, Weissing FJ (2020) Understanding ‘non-genetic’ inheritance: insights from molecular-evolutionary crosstalk. Trends Ecol Evol 35(12):1078–1089. https://doi.org/10.1016/j.tree.2020.08.011
Alabert C, Barth TK, Reverón-Gómez N, Sidoli S, Schmidt A, Jensen ON, Imhof A, Groth A (2015) Two distinct modes for propagation of histone PTMs across the cell cycle. Genes Dev 29(6):585–590. https://doi.org/10.1101/gad.256354.114
Arias-Carrión O, Stamelou M, Murillo-Rodríguez E, Menéndez-González M, Pöppel E (2010) Dopaminergic reward system: a short integrative review. Int Arch Med 3(1):24. https://doi.org/10.1186/1755-7682-3-24
Axsom JE, Libonati JR (2019) Impact of parental exercise on epigenetic modifications inherited by offspring: a systematic review. Physiol Rep 7(22):e14287. https://doi.org/10.14814/phy2.14287
Azzi S, Sas TC, Koudou Y, Le Bouc Y, Souberbielle JC, Dargent-Molina P, Netchine I, Charles MA (2014) Degree of methylation of ZAC1 (PLAGL1) is associated with prenatal and post-natal growth in healthy infants of the EDEN mother child cohort. Epigenetics 9(3):338–345. https://doi.org/10.4161/epi.27387
Bale TL (2011) Sex differences in prenatal epigenetic programming of stress pathways. Stress 14(4):348–356. https://doi.org/10.3109/10253890.2011
Balhorn R (2007) The protamine family of sperm nuclear proteins. Genome Biol 8(9):227. https://doi.org/10.1186/gb-2007-8-9-227
Barres R, Zierath JR (2016) The role of diet and exercise in the transgenerational epigenetic landscape of T2DM. Nat Rev Endocrinol 12(8):441–451. https://doi.org/10.1038/nrendo.2016.87
Barrón-Cabrera E, Ramos-Lopez O, González-Becerra K, Riezu-Boj JI, Milagro FI, Martínez-López E, Martínez JA (2019) Epigenetic modifications as outcomes of exercise interventions related to specific metabolic alterations: a systematic review. Lifestyle Genom 12(1–6):25–44. https://doi.org/10.1159/000503289
Ben Maamar M, Nilsson E, Thorson JLM, Beck D, Skinner MK (2020) Epigenome-wide association study for transgenerational disease sperm epimutation biomarkers following ancestral exposure to jet fuel hydrocarbons. Reprod Toxicol 98:61–74. https://doi.org/10.1016/j.reprotox.2020.08.010
Benito E, Kerimoglu C, Ramachandran B, Pena-Centeno T, Jain G, Stilling RM, Islam MR, Capece V, Zhou Q, Edbauer D, Dean C, Fischer A (2018) RNA-dependent intergenerational inheritance of enhanced synaptic plasticity after environmental enrichment. Cell Rep 23(2):546–554. https://doi.org/10.1016/j.celrep.2018.03.059
Bertozzi TM, Ferguson-Smith AC (2020) Metastable epialleles and their contribution to epigenetic inheritance in mammals. Semin Cell Dev Biol 97:93–105. https://doi.org/10.1016/j.semcdb.2019.08.002
Bhattacharya S, Fontaine A, MacCallum PE, Drover J, Blundell J (2019) Stress across generations: DNA Methylation as a potential mechanism underlying intergenerational effects of stress in both post-traumatic stress disorder and pre-clinical predator stress rodent models. Front Behav Neurosci 13:113. https://doi.org/10.3389/fnbeh.2019.00113
Birnbaum RY, Clowney EJ, Agamy O, Kim MJ, Zhao J, Yamanaka T, Pappalardo Z, Clarke SL, Wenger AM, Nguyen L, Gurrieri F, Everman DB, Schwartz CE, Birk OS, Bejerano G, Lomvardas S, Ahituv N (2012) Coding exons function as tissue-specific enhancers of nearby genes. Genome Res 22(6):1059–1068. https://doi.org/10.1101/gr.133546.111
Blake GE, Watson ED (2016) Unravelling the complex mechanisms of transgenerational epigenetic inheritance. Curr Opin Chem Biol 33:101–107. https://doi.org/10.1016/j.cbpa.2016.06.008
Blattler A, Yao L, Witt H, Guo Y, Nicolet CM, Berman BP, Farnham PJ (2014) Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes. Genome Biol 15:469. https://doi.org/10.1186/s13059-014-0469-0
Bošković A, Rando OJ (2018) Transgenerational epigenetic inheritance. Annu Rev Genet 52:21–41. https://doi.org/10.1146/annurev-genet-120417-031404
Braithwaite EC, Kundakovic M, Ramchandani PG, Murphy SE, Champagne FA (2015) Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation. Epigenetics 10(5):408–417. https://doi.org/10.1080/15592294.2015.1039221
Braun K, Champagne FA (2014) Paternal influences on offspring development: behavioural and epigenetic pathways. J Neuroendocrinol 26(10):697–706. https://doi.org/10.1111/jne.12174
Bredy TW, Wu H, Crego C, Zellhoefer J, Sun YE, Barad M (2007) Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear. Learn Mem 14(4):268–276. https://doi.org/10.1101/lm.500907
Bygren LO, Tinghög P, Carstensen J, Edvinsson S, Kaati G, Pembrey ME, Sjöström M (2014) Change in paternal grandmothers’ early food supply influenced cardiovascular mortality of the female grandchildren. BMC Genet 15:12. https://doi.org/10.1186/1471-2156-15-12
Callaway LK, Colditz PB, Byrne NM, Lingwood BE, Rowlands IJ, Foxcroft K, McIntyre, Bambino Group (2010) Prevention of gestational diabetes: feasibility issues for an exercise intervention in obese pregnant women. Diabetes Care 33(7):1457–1459. https://doi.org/10.2337/dc09-2336
Carlos-Reyes Á, López-González JS, Meneses-Flores M, Gallardo-Rincón D, Ruíz-García E, Marchat LA, Astudillo-de la Vega H, Hernández de la Cruz ON, López-Camarillo C (2019) Dietary compounds as epigenetic modulating agents in cancer. Front Genet 10:79. https://doi.org/10.3389/fgene.2019.00079
Carone BR, Fauquier L, Habib N, Shea JM, Hart CE, Li R, Bock C, Li C, Gu H, Zamore PD, Meissner A, Weng Z, Hofmann HA, Friedman N, Rando OJ (2010) Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143(7):1084–1096. https://doi.org/10.1016/j.cell.2010.12.008
Carpenter BL, Zhou W, Madaj Z, DeWitt AK, Ross JP, Grønbæk K, Liang G, Clark SJ, Molloy PL, Jones PA (2018) Mother–child transmission of epigenetic information by tunable polymorphic imprinting. PNAS 115(51):E11970–E11977. https://doi.org/10.1073/pnas.1815005115
Casas E, Vavouri T (2014) Sperm epigenomics: challenges and opportunities. Front Genet 5:330. https://doi.org/10.3389/fgene.2014.00330
Casas E, Vavouri T (2020) Mechanisms of epigenetic inheritance of variable traits through the germline. Reproduction 159(6):R251–R263. https://doi.org/10.1530/REP-19-0340
Chavez SL, McElroy SL, Bossert NL, De Jonge CJ, Rodriguez MV, Leong DE, Behr B, Westphal LM, Reijo Pera RA (2014) Comparison of epigenetic mediator expression and function in mouse and human embryonic blastomeres. Hum Mol Genet 23(18):4970–4984. https://doi.org/10.1093/hmg/ddu212
Chen Q, Yan W, Duan E (2016) Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications. Nat Rev Genet 17:733–743. https://doi.org/10.1038/nrg.2016.106
Christensen DP, Dahllöf M, Lundh M, Rasmussen DN, Nielsen MD, Billestrup N, Grunnet LG, Mandrup-Poulsen T (2011) Histone deacetylase (HDAC) inhibition as a novel treatment for diabetes mellitus. Mol Med 17(5–6):378–390. https://doi.org/10.2119/molmed.2011.00021
Cimino S, Cerniglia L, Ballarotto G, Marzilli E, Pascale E, D’Addario C, Adriani W, Tambelli R (2018) DNA Methylation at the DAT promoter and risk for psychopathology: intergenerational transmission between school-age youths and their parents in a community sample. Front Psychiatry 8:303. https://doi.org/10.3389/fpsyt.2017.00303
Danielson CK, Hankin BL, Badanes LS (2015) Youth offspring of mothers with posttraumatic stress disorder have altered stress reactivity in response to a laboratory stressor. Psychoneuroendocrinology 53:170–178. https://doi.org/10.1016/j.psyneuen.2015.01.001
Day J, Savani S, Krempley BD, Nguyen M, Kitlinska JB (2016) Influence of paternal preconception exposures on their offspring: through epigenetics to phenotype. Am J Stem Cells 5(1):11–18
De Majo F, Calore M (2018) Chromatin remodelling and epigenetic state regulation by non-coding RNAs in the diseased heart. Noncoding RNA Res 3(1):20–28. https://doi.org/10.1016/j.ncrna.2018.02.003. Erratum in: Noncoding RNA Res 5(4):220–221
Denham J, O’Brien BJ, Harvey JT, Charchar FJ (2015) Genome-wide sperm DNA methylation changes after 3 months of exercise training in humans. Epigenomics 7:5. https://doi.org/10.2217/epi.15.29
Dolinoy DC, Faulk C (2012) Introduction: the use of animal models to advance epigenetic science. ILAR J 53(3–4):227–231. https://doi.org/10.1093/ilar.53.3-4.227
Donkin I, Barrès R (2018) Sperm epigenetics and influence of environmental factors. Mol Metab 14:1–11. https://doi.org/10.1016/j.molmet.2018.02.006
Donohoe DR, Bultman SJ (2012) Metaboloepigenetics: interrelationships between energy metabolism and epigenetic control of gene expression. J Cell Physiol 227(9):3169–3177. https://doi.org/10.1002/jcp.24054
Erkek S, Hisano M, Liang CY, Gill M, Murr R, Dieker J, Schübeler D, van der Vlag J, Stadler MB, Peters AH (2013) Molecular determinants of nucleosome retention at CpG-rich sequences in mouse spermatozoa. Nat Struct Mol Biol 20(7):868–875. https://doi.org/10.1038/nsmb.2599
Ferrari L, Vicenzi M, Tarantini L, Barretta F, Sironi S, Baccarelli AA, Guazzi M, Bollati V (2019) Effects of physical exercise on endothelial function and DNA methylation. Int J Environ Res Public Health 16(14):2530. https://doi.org/10.3390/ijerph16142530
Francastel C, Magdinier F (2019) DNA methylation in satellite repeats disorders. Essays Biochem 63(6):757–771. https://doi.org/10.1042/EBC20190028
Fullston T, Ohlsson Teague EM, Palmer NO, DeBlasio MJ, Mitchell M, Corbett M, Print CG, Owens JA, Lane M (2013) 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. FASEB J 27(10):4226–4243. https://doi.org/10.1096/fj.12-224048
Galan C, Krykbaeva M, Rando OJ (2020) Early life lessons: the lasting effects of germline epigenetic information on organismal development. Mol Metab 38:100924. https://doi.org/10.1016/j.molmet.2019.12.004
Galaris D, Skiada V, Barbouti A (2008) Redox signalling and cancer: the role of “labile” iron. Cancer Lett 266:21–29. https://doi.org/10.1016/j.canlet.2008.02.038
Gao Z, Zhang J, Bonasio R, Strino F, Sawai A, Parisi F, Kluger Y, Reinberg D (2012) PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes. Mol Cell 45(3):344–356. https://doi.org/10.1016/j.molcel.2012.01.002
Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P, Prados J, Farinelli L, Miska E, Mansuy IM (2014) Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat Neurosci 17(5):667–669. https://doi.org/10.1038/nn.3695
García-Calzón S, Perfilyev A, de Mello VD, Pihlajamäki J, Ling C (2018) Sex differences in the methylome and transcriptome of the human liver and circulating HDL-cholesterol levels. J Clin Endocrinol Metab 103(12):4395–4408. https://doi.org/10.1210/jc.2018-00423
Gerardin P, Wendland J, Bodeau N, Galin A, Bialobos S, Tordjman S, Mazet P, Darbois Y, Nizard J, Dommergues M, Cohen D (2011) Depression during pregnancy: is the developmental impact earlier in boys? A prospective case-control study. J Clin Psychiatry 72(3):378–387. https://doi.org/10.4088/JCP.09m05724blu
Giana G, Romano E, Porfirio MC, D’Ambrosio R, Giovinazzo S, Troianiello M, Barlocci E, Travaglini D, Granstrem O, Pascale E, Tarani L, Curatolo P, Laviola G, Adriani W (2015) Detection of auto-antibodies to DAT in the serum: interactions with DAT genotype and psycho-stimulant therapy for ADHD. J Neuroimmunol 278:212–222. https://doi.org/10.1016/j.jneuroim.2014.11.008
Gòdia M, Swanson G, Krawetz SA (2018) A history of why fathers’ RNA matters. Biol Reprod 99(1):147–159. https://doi.org/10.1093/biolre/ioy007
Grazioli E, Dimauro I, Mercatelli N, Wang G, Pitsiladis Y, Di Luigi L, Caporossi D (2017) Physical activity in the prevention of human diseases: role of epigenetic modifications. BMC Genom 18(Suppl 8):802. https://doi.org/10.1186/s12864-017-4193-5
Grossniklaus U, Kelly WG, Kelly B, Ferguson-Smith AC, Pembrey M, Lindquist S (2013) Transgenerational epigenetic inheritance: how important is it? Nat Rev Genet 14(3):228–235. https://doi.org/10.1038/nrg3435
Gu L, Wang Q, Sun Q-Y (2010) Histone modifications during mammalian oocyte maturation: dynamics, regulation and functions. Cell Cycle 9(10):1942–1950. https://doi.org/10.4161/cc.9.10.11599
Guibert S, Forné T, Weber M (2012) Global profiling of DNA methylation erasure in mouse primordial germ cells. Genome Res 22(4):633–641. https://doi.org/10.1101/gr.130997.111
Guo F, Li X, Liang D, Li T, Zhu P, Guo H, Wu X, Wen L, Gu TP, Hu B, Walsh CP, Li J, Tang F, Xu GL (2014a) Active and passive demethylation of male and female pronuclear DNA in the mammalian zygote. Cell Stem Cell 15(4):447–459. https://doi.org/10.1016/j.stem.2014.08.003
Guo H, Zhu P, Yan L, Li R, Hu B, Lian Y, Yan J, Ren X, Lin S, Li J, Jin X, Shi X, Liu P, Wang X, Wang W, Wei Y, Li X, Guo F, Wu X, Fan X, Yong J, Wen L, Xie SX, Tang F, Qiao J (2014b) The DNA methylation landscape of human early embryos. Nature 511(7511):606–610. https://doi.org/10.1038/nature13544
Harvey ZH, Chakravarty AK, Futia RA, Jarosz DF (2020) A prion epigenetic switch establishes an active chromatin state. Cell 180(5):928-940.e14. https://doi.org/10.1016/j.cell.2020.02.014
Heard E, Martienssen RA (2014) Transgenerational epigenetic inheritance: myths and mechanisms. Cell 157(1):95–109. https://doi.org/10.1016/j.cell.2014.02.045
Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, Slagboom PE, Lumey LH (2008) Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA 105(44):17046–17049. https://doi.org/10.1073/pnas.0806560105
Hodes GE, Walker DM, Labonté B, Nestler EJ, Russo SJ (2017) Understanding the epigenetic basis of sex differences in depression. J Neurosci Res 95(1–2):692–702. https://doi.org/10.1002/jnr.23876
Horsthemke B (2018) A critical view on transgenerational epigenetic inheritance in humans. Nat Commun 9:2973. https://doi.org/10.1038/s41467-018-05445-5
Huen K, Harley K, Kogut K, Rauch S, Eskenazi B, Holland N (2016) DNA methylation of LINE-1 and Alu repetitive elements in relation to sex hormones and pubertal timing in Mexican-American children. Pediatr Res 79:855–862. https://doi.org/10.1038/pr.2016.31
Ingerslev LR, Donkin I, Fabre O, Versteyhe S, Mechta M, Pattamaprapanont P, Mortensen B, Krarup NT, Barrès R (2018) Endurance training remodels sperm-borne small RNA expression and methylation at neurological gene hotspots. Clin Epigenet 10:12. https://doi.org/10.1186/s13148-018-0446-7
Jablonka E (2017) The evolutionary implications of epigenetic inheritance. Interface Focus 7(5):20160135. https://doi.org/10.1098/rsfs.2016.0135
Jeong SW, Kim SH, Kang SH, Kim HJ, Yoon CH, Youn TJ, Chae IH (2019) Mortality reduction with physical activity in patients with and without cardiovascular disease. Eur Heart J 40(43):3547–3555. https://doi.org/10.1093/eurheartj/ehz564
Jiang S, Postovit L, Cattaneo A, Binder EB, Aitchison KJ (2019) Epigenetic modifications in stress response genes associated with childhood trauma. Front Psychiatry 10:808. https://doi.org/10.3389/fpsyt.2019.00808
John RM, Rougeulle C (2018) Developmental epigenetics: phenotype and the flexible epigenome. Front Cell Dev Biol 6:130. https://doi.org/10.3389/fcell.2018.00130
Kader F, Ghai M (2017) DNA methylation-based variation between human populations. Mol Genet Genom 292(1):5–35. https://doi.org/10.1007/s00438-016-1264-2
Kang SC, Lee BM (2005) DNA methylation of estrogen receptor alpha gene by phthalates. J Toxicol Environ Health A 68(23–24):1995–2003. https://doi.org/10.1080/15287390491008913
Kanwal R, Gupta S (2012) Epigenetic modifications in cancer. Clin Genet 81(4):303–311. https://doi.org/10.1111/j.1399-0004.2011.01809
Keyhan S, Burke E, Schrott R, Huang Z, Grenier C, Price T, Raburn D, Corcoran DL, Soubry A, Hoyo C, Murphy SK (2021) Male obesity impacts DNA methylation reprogramming in sperm. Clin Epigenet 13(1):17. https://doi.org/10.1186/s13148-020-00997-0
Kim JH, Rozek LS, Soliman AS, Sartor MA, Hablas A, Seifeldin IA, Colacino JA, Weinhouse C, Nahar MS, Dolinoy DC (2013) Bisphenol A-associated epigenomic changes in prepubescent girls: a cross-sectional study in Gharbiah. Egypt Environ Health 12:33. https://doi.org/10.1186/1476-069X-12-33
Klosin A, Casas E, Hidalgo-Carcedo C, Vavouri T, Lehner B (2017) Transgenerational transmission of environmental information in C. elegans. Science 356(6335):320–323. https://doi.org/10.1126/science.aah6412
Kopsida E, Mikaelsson MA, Davies W (2011) The role of imprinted genes in mediating susceptibility to neuropsychiatric disorders. Horm Behav 59(3):375–382. https://doi.org/10.1016/j.yhbeh.2010.04.005
Kowiański P, Lietzau G, Czuba E, Waśkow M, Steliga A, Moryś J (2018) BDNF: a key factor with multipotent impact on brain signalling and synaptic plasticity. Cell Mol Neurobiol 38(3):579–593. https://doi.org/10.1007/s10571-017-0510-4
Lacal I, Ventura R (2018) Epigenetic inheritance: concepts, mechanisms and perspectives. Front Mol Neurosci 11:292. https://doi.org/10.3389/fnmol.2018.00292
Lahey BB, Rathouz PJ, Lee SS, Chronis-Tuscano A, Pelham WE, Waldman ID, Cook EH (2011) Interactions between early parenting and a polymorphism of the child’s dopamine transporter gene in predicting future child conduct disorder symptoms. J Abnorm Psychol 120(1):33–45. https://doi.org/10.1037/a0021133
Laker RC, Lillard TS, Okutsu M, Zhang M, Hoehn KL, Connelly JJ, Yan Z (2014) Exercise prevents maternal high-fat diet-induced hypermethylation of the Pgc-1α gene and age-dependent metabolic dysfunction in the offspring. Diabetes 63(5):1605–1611. https://doi.org/10.2337/db13-1614
Legoff L, D’Cruz SC, Tevosian S, Primig M, Smagulova F (2019) Transgenerational inheritance of environmentally induced epigenetic alterations during mammalian development. Cells 8(12):1559. https://doi.org/10.3390/cells8121559
Linschooten JO, Verhofstad N, Gutzkow K, Olsen AK, Yauk C, Oligschläger Y, Brunborg G, van Schooten FJ, Godschalk RW (2013) Paternal lifestyle as a potential source of germline mutations transmitted to offspring. FASEB J 27(7):2873–2879. https://doi.org/10.1096/fj.13-227694
Liu Y, Hoyo C, Murphy S, Huang Z, Overcash F, Thompson J, Brown H, Murtha AP (2013) DNA methylation at imprint regulatory regions in preterm birth and infection. Am J Obstet Gynecol 208(5):395.e1–7. https://doi.org/10.1016/j.ajog.2013.02.006
Liu S, Yu H, Liu Y, Liu X, Zhang Y, Bu C, Yuan S, Chen Z, Xie G, Li W, Xu B, Yang J, He L, Jin T, Xiong Y, Sun L, Liu X, Han C, Cheng Z, Liang J, Shang Y (2017) Chromodomain protein CDYL acts as a Crotonyl-CoA Hydratase to regulate histone crotonylation and spermatogenesis. Mol Cell 67(5):853-866.e5. https://doi.org/10.1016/j.molcel.2017.07.011
Liu X, Tong Z, Chen K, Hu X, Jin H, Hou M (2018) The role of miRNA-132 against apoptosis and oxidative stress in heart failure. Biomed Res Int 2018:3452748. https://doi.org/10.1155/2018/3452748
Loke YJ, Galati JC, Morley R, Joo EJ, Novakovic B, Li X, Weinrich B, Carson N, Ollikainen M, Ng HK, Andronikos R, Aziz NK, Saffery R, Craig JM (2013) Association of maternal and nutrient supply line factors with DNA methylation at the imprinted IGF2/H19 locus in multiple tissues of newborn twins. Epigenetics 8(10):1069–1079. https://doi.org/10.4161/epi.25908
Loke YJ, Galati JC, Saffery R, Craig JM (2015) Association of in vitro fertilization with global and IGF2/H19 methylation variation in newborn twins. J Dev Orig Health Dis 6(2):115–124. https://doi.org/10.1017/S2040174415000161
López P, Castro A, Flórez M, Miranda K, Aranda P, Sánchez-González C, Llopis J, Arredondo M (2018) miR-155 and miR-122 expression of spermatozoa in obese subjects. Front Genet 9:175. https://doi.org/10.3389/fgene.2018.00175
Lu S, Niu Z, Chen Y, Tu Q, Zhang Y, Chen W, Tong W, Zhang Z (2018) Repetitive element DNA methylation is associated with menopausal age. Aging Dis 9(3):435–443. https://doi.org/10.14336/AD.2017.0810
Maschietto M, Bastos LC, Tahira AC, Bastos EP, Euclydes VL, Brentani A, Fink G, de Baumont A, Felipe-Silva A, Francisco RP, Gouveia G, Grisi SJ, Escobar AM, Moreira-Filho CA, Polanczyk GV, Miguel EC, Brentani H (2017) Sex differences in DNA methylation of the cord blood are related to sex-bias psychiatric diseases. Sci Rep 7:44547. https://doi.org/10.1038/srep44547
Masuyama H, Mitsui T, Eguchi T, Tamada S, Hiramatsu Y (2016) The effects of paternal high-fat diet exposure on offspring metabolism with epigenetic changes in the mouse adiponectin and leptin gene promoters. Am J Physiol Endocrinol Metab 311(1):E236–E245. https://doi.org/10.1152/ajpendo.00095.2016
Mayr E (1980). Prologue: some thoughts on the history of the evolutionary synthesis. In: Mayr E, Provine WB (eds) The evolutionary synthesis: perspectives on the unification of biology. Harvard University Press, Cambridge, pp 1–48. ISBN 9780674865389. http://hdl.handle.net/10822/548441
Mayr E (1982) The growth of biological thought: diversity, evolution, and inheritance. Belknap Press, Cambridge. ISBN 0-674-36446-5. epitropakisg.gr/grigorise/Mayr_GrowthOfBiologicalThought.pdf
McCullough LE, Mendez MA, Miller EE, Murtha AP, Murphy SK, Hoyo C (2015) Associations between prenatal physical activity, birth weight, and DNA methylation at genomically imprinted domains in a multiethnic newborn cohort. Epigenetics 10(7):597–606. https://doi.org/10.1080/15592294.2015.1045181
McGowan PO, Sasaki A, D’Alessio AC, Dymov S, Labonté B, Szyf M, Turecki G, Meaney MJ (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12(3):342–348. https://doi.org/10.1038/nn.2270
McPherson NO, Owens JA, Fullston T, Lane M (2015) Preconception diet or exercise intervention in obese fathers normalizes sperm microRNA profile and metabolic syndrome in female offspring. Am J Physiol Endocrinol Metab 308:E805–E821. https://doi.org/10.1152/ajpendo.0013.2015
Millership SJ, Van de Pette M, Withers DJ (2019) Genomic imprinting and its effects on postnatal growth and adult metabolism. Cell Mol Life Sci 76(20):4009–4021. https://doi.org/10.1007/s00018-019-03197-z
Minkina O, Hunter CP (2018) Intergenerational transmission of gene regulatory information in Caenorhabditis elegans. Trends Genet 34(1):54–64. https://doi.org/10.1016/j.tig.2017.09.012
Miska EA, Ferguson-Smith AC (2016) Transgenerational inheritance: models and mechanisms of non-DNA sequence-based inheritance. Science 354:59–63. https://doi.org/10.1126/science.aaf4945
Monsey MS, Ota KT, Akingbade IF, Hong ES, Schafe GE (2011) Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala. PLoS ONE 6(5):e19958. https://doi.org/10.1371/journal.pone.0019958
Mørkve Knudsen T, Rezwan FI, Jiang Y, Karmaus W, Svanes C, Holloway JW (2018) Transgenerational and intergenerational epigenetic inheritance in allergic diseases. J Allergy Clin Immunol 142(3):765–772. https://doi.org/10.1016/j.jaci.2018.07.007
Mørkve Knudsen GT, Rezwan FI, Johannessen A, Skulstad SM, Bertelsen RJ, Real FG, Krauss-Etschmann S, Patil V, Jarvis D, Arshad SH, Holloway JW, Svanes C (2019) Epigenome-wide association of father’s smoking with offspring DNA methylation: a hypothesis-generating study. Environ Epigenet 5(4):dvz023. https://doi.org/10.1093/eep/dvz023
Moussa HF, Bsteh D, Yelagandula R, Pribitzer C, Stecher K, Bartalska K, Michetti L, Wang J, Zepeda-Martinez JA, Elling U, Stuckey JI, James LI, Frye SV, Bell O (2019) Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing. Nat Commun 10(1):1931. https://doi.org/10.1038/s41467-019-09628-6
Mulligan CJ, D’Errico NC, Stees J, Hughes DA (2012) Methylation changes at NR3C1 in newborns associate with maternal prenatal stress exposure and newborn birth weight. Epigenetics 7(8):853–857. https://doi.org/10.4161/epi.21180
Nestler EJ (2016) Transgenerational epigenetic contributions to stress responses: fact or fiction? PLoS Biol 14(3):e1002426. https://doi.org/10.1371/journal.pbio.1002426. Erratum in: PLoS Biol 14(6):e1002486
Newman DJ, Cragg GM (2020) Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod 83(3):770–803. https://doi.org/10.1021/acs.jnatprod.9b01285
Newman AC, Maddocks ODK (2017) One-carbon metabolism in cancer. Br J Cancer 116(12):1499–1504. https://doi.org/10.1038/bjc.2017.118
Nixon B, Stanger SJ, Mihalas BP, Reilly JN, Anderson AL, Tyagi S, Holt JE, McLaughlin EA (2015) The microRNA signature of mouse spermatozoa is substantially modified during epididymal maturation. Biol Reprod 93:91. https://doi.org/10.1095/biolreprod.115.132209
Oberlander TF, Weinberg J, Papsdorf M, Grunau R, Misri S, Devlin AM (2008) Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 3:97–106. https://doi.org/10.4161/epi.3.2.6034
Pang TYC, Short AK, Bredy TW, Hannan AJ (2017) Transgenerational paternal transmission of acquired traits: stress-induced modification of the sperm regulatory transcriptome and offspring phenotypes. Curr Opin Behav Sci 14:140–147. https://doi.org/10.1016/j.cobeha.2017.02.007
Papin C, Ibrahim A, Gras SL, Velt A, Stoll I, Jost B, Menoni H, Bronner C, Dimitrov S, Hamiche A (2017) Combinatorial DNA methylation codes at repetitive elements. Genome Res 27(6):934–946. https://doi.org/10.1101/gr.213983.116
Paul KC, Chuang YH, Cockburn M, Bronstein JM, Horvath S, Ritz B (2018) Organophosphate pesticide exposure and differential genome-wide DNA methylation. Sci Total Environ 645:1135–1143. https://doi.org/10.1016/j.scitotenv.2018.07.143
Pauwels S, Ghosh M, Duca RC, Bekaert B, Freson K, Huybrechts I, Langie SAS, Koppen G, Devlieger R, Godderis L (2017) Maternal intake of methyl-group donors affects DNA methylation of metabolic genes in infants. Clin Epigenet 9:16. https://doi.org/10.1186/s13148-017-0321-y
Pembrey ME, Bygren LO, Kaati G, Edvinsson S, Northstone K, Sjöström M, Golding J, ALSPAC Study Team (2006) Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet 14(2):159–166. https://doi.org/10.1038/sj.ejhg.5201538
Perez MF, Lehner B (2019) Intergenerational and transgenerational epigenetic inheritance in animals. Nat Cell Biol 21(2):143–151. https://doi.org/10.1038/s41556-018-0242-9
Perroud N, Rutembesa E, Paoloni-Giacobino A, Mutabaruka J, Mutesa L, Stenz L, Malafosse A, Karege F (2014) The Tutsi genocide and transgenerational transmission of maternal stress: epigenetics and biology of the HPA axis. World J Biol Psychiatry 15(4):334–345. https://doi.org/10.3109/15622975.2013.866693
Provençal N, Binder EB (2015) The effects of early life stress on the epigenome: from the womb to adulthood and even before. Exp Neurol 268:10–20. https://doi.org/10.1016/j.expneurol.2014.09.001
Puschendorf M, Terranova R, Boutsma E, Mao X, Isono K, Brykczynska U, Kolb C, Otte AP, Koseki H, Orkin SH, van Lohuizen M, Peters AH (2008) PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos. Nat Genet 40(4):411–420. https://doi.org/10.1038/ng.99
Qureshi IA, Mehler MF (2010) Genetic and epigenetic underpinnings of sex differences in the brain and in neurological and psychiatric disease susceptibility. Prog Brain Res 186:77–95. https://doi.org/10.1016/B978-0-444-53630-3.00006-3
Radtke KM, Ruf M, Gunter HM, Dohrmann K, Schauer M, Meyer A, Elbert T (2011) Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor. Transl Psychiatry 1(7):e21. https://doi.org/10.1038/tp.2011.21
Rassoulzadegan M, Grandjean V, Gounon P, Vincent S, Gillot I, Cuzin F (2006) RNA-mediated non-Mendelian inheritance of an epigenetic change in the mouse. Nature 441:469–474. https://doi.org/10.1038/nature04674
Reilly JN, McLaughlin EA, Stanger SJ, Anderson AL, Hutcheon K, Church K, Mihalas BP, Tyagi S, Holt JE, Eamens AL, Nixon B (2016) Characterisation of mouse epididymosomes reveals a complex profile of microRNAs and a potential mechanism for modification of the sperm epigenome. Sci Rep 6:31794. https://doi.org/10.1038/srep31794
Remely M, Stefanska B, Lovrecic L, Magnet U, Haslberger AG (2015) Nutriepigenomics: the role of nutrition in epigenetic control of human diseases. Curr Opin Clin Nutr Metab Care 18(4):328–333. https://doi.org/10.1097/MCO.0000000000000180
Roberts AL, Gladish N, Gatev E, Jones MJ, Chen Y, Macisaac JL, Tworoger SS, Austin SB, Tanrikut C, Chavarro JE, Baccarelli AA, Kobor MS (2018) Exposure to childhood abuse is associated with human sperm DNA methylation. Transl Psychiatry 8:194. https://doi.org/10.1038/s41398-018-0252-1
Rodgers AB, Morgan CP, Bronson SL, Revello S, Bale TL (2013) Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. J Neurosci 33(21):9003–9012. https://doi.org/10.1523/JNEUROSCI.0914-13.2013
Rodgers AB, Morgan CP, Leu NA, Bale TL (2015) Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress. Proc Natl Acad Sci USA 112(44):13699–13704. https://doi.org/10.1073/pnas.1508347112
Rönn T, Volkov P, Davegårdh C, Dayeh T, Hall E, Olsson AH, Nilsson E, Tornberg A, Dekker Nitert M, Eriksson KF, Jones HA, Groop L, Ling C (2013) A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet 9(6):e1003572. https://doi.org/10.1371/journal.pgen.1003572
Schagdarsurengin U, Steger K (2016) Epigenetics in male reproduction: effect of paternal diet on sperm quality and offspring health. Nat Rev Urol 13(10):584–595. https://doi.org/10.1038/nrurol.2016.157
Sciamanna I, Serafino A, Shapiro JA, Spadafora C (2019) The active role of spermatozoa in transgenerational inheritance. Proc Biol Sci 286(1909):20191263. https://doi.org/10.1098/rspb.2019.1263
Seisenberger S, Andrews S, Krueger F, Arand J, Walter J, Santos F, Popp C, Thienpont B, Dean W, Reik W (2012) The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol Cell 48(6):849–862. https://doi.org/10.1016/j.molcel.2012.11.001
Sen A, Heredia N, Senut MC, Land S, Hollocher K, Lu X, Dereski MO, Ruden DM (2015) Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren. Sci Rep 5:14466. https://doi.org/10.1038/srep14466
Senaldi L, Smith-Raska M (2020) Evidence for germline non-genetic inheritance of human phenotypes and diseases. Clin Epigenet 1:136. https://doi.org/10.1186/s13148-020-00929-y
Seong KH, Li D, Shimizu H, Nakamura R, Ishii S (2011) Inheritance of stress-induced, ATF-2-dependent epigenetic change. Cell 145(7):1049–1061. https://doi.org/10.1016/j.cell.2011.05.029
Serpeloni F, Radtke K, de Assis SG, Henning F, Nätt D, Elbert T (2017) Grandmaternal stress during pregnancy and DNA methylation of the third generation: an epigenome-wide association study. Transl Psychiatry 7(8):e1202. https://doi.org/10.1038/tp.2017.153
Singmann P, Shem-Tov D, Wahl S, Grallert H, Fiorito G, Shin SY, Schramm K, Wolf P, Kunze S, Baran Y, Guarrera S, Vineis P, Krogh V, Panico S, Tumino R, Kretschmer A, Gieger C, Peters A, Prokisch H, Relton CL, Matullo G, Illig T, Waldenberger M, Halperin E (2015) Characterization of whole-genome autosomal differences of DNA methylation between men and women. Epigenet Chromatin 8:43. https://doi.org/10.1186/s13072-015-0035-3
Skinner MK, Ben Maamar M, Sadler-Riggleman I, Beck D, Nilsson E, McBirney M, Klukovich R, Xie Y, Tang C, Yan W (2018) Alterations in sperm DNA methylation, non-coding RNA and histone retention associate with DDT-induced epigenetic transgenerational inheritance of disease. Epigenet Chromatin 11(1):8. https://doi.org/10.1186/s13072-018-0178-0
Skvortsova K, Iovino N, Bogdanović O (2018) Functions and mechanisms of epigenetic inheritance in animals. Nat Rev Mol Cell Biol 19(12):774–790. https://doi.org/10.1038/s41580-018-0074-2
Soubry A (2015) Epigenetic inheritance and evolution: a paternal perspective on dietary influences. Prog Biophys Mol Biol 118(1–2):79–85. https://doi.org/10.1016/j.pbiomolbio.2015.02.008
Soubry A (2017) Epigenetics as a driver of developmental origins of health and disease: did we forget the fathers? BioEssays 40:1700113. https://doi.org/10.1002/bies.201700113
Soubry A, Schildkraut JM, Murtha A, Wang F, Huang Z, Bernal A, Kurtzberg J, Jirtle RL, Murphy SK, Hoyo C (2013) Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort. BMC Med 11:29. https://doi.org/10.1186/1741-7015-11-29
Soubry A, Hoyo C, Jirtle RL, Murphy SK (2014) A paternal environmental legacy: evidence for epigenetic inheritance through the male germ line. BioEssays 36(4):359–371. https://doi.org/10.1002/bies.201300113
Soubry A, Murphy SK, Wang F, Huang Z, Vidal AC, Fuemmeler BF, Kurtzberg J, Murtha A, Jirtle RL, Schildkraut JM, Hoyo C (2015) Newborns of obese parents have altered DNA methylation patterns at imprinted genes. Int J Obes 39(4):650–657. https://doi.org/10.1038/ijo.2013.193
Soubry A, Hoyo C, Butt CM, Fieuws S, Price TM, Murphy SK, Stapleton HM (2017) Human exposure to flame- retardants is associated with aberrant DNA methylation at imprinted genes in sperm. Environ Epigenet 3(1):dvx003. https://doi.org/10.1093/eep/dvx003
Spindler C, Segabinazi E, Meireles ALF, Piazza FV, Mega F, Dos Santos SG, Achaval M, Elsner VR, Marcuzzo S (2019) Paternal physical exercise modulates global DNA methylation status in the hippocampus of male rat offspring. Neural Regen Res 14(3):491–500. https://doi.org/10.4103/1673-5374.245473
Steegers-Theunissen RP, Obermann-Borst SA, Kremer D, Lindemans J, Siebel C, Steegers EA, Slagboom PE, Heijmans BT (2009) Periconceptional maternal folic acid use of 400 µg per day is related to increased methylation of the IGF2 gene in the very young child. PLoS ONE 4(11):e7845. https://doi.org/10.1371/journal.pone.0007845
Suen JL, Wu TT, Li YH, Lee CL, Kuo FC, Yan PS, Wu CF, Tran M, Wang CJ, Hung CH, Wu MT, Chan MWY, Huang SK (2020) Environmental factor-mediated transgenerational inheritance of Igf2r hypomethylation and pulmonary allergic response via targeting dendritic cells. Front Immunol 11:603831. https://doi.org/10.3389/fimmu.2020.603831
Tikhodeyev ON (2018) The mechanisms of epigenetic inheritance: how diverse are they? Biol Rev Camb Philos Soc 93(4):1987–2005. https://doi.org/10.1111/brv.12429
Titus-Ernstoff L, Troisi R, Hatch EE, Wise LA, Palmer J, Hyer M, Kaufman R, Adam E, Strohsnitter W, Noller K, Herbst AL, Gibson-Chambers J, Hartge P, Hoover RN (2006) Menstrual and reproductive characteristics of women whose mothers were exposed in utero to diethylstilbestrol (DES). Int J Epidemiol 35(4):862–868. https://doi.org/10.1093/ije/dyl106
Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H, Stein AD, Slagboom PE, Heijmans BT (2009) DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet 18(21):4046–4053. https://doi.org/10.1093/hmg/ddp353
Tunc O, Tremellen K (2009) Oxidative DNA damage impairs global sperm DNA methylation in infertile men. J Assist Reprod Genet 26(9–10):537–544. https://doi.org/10.1007/s10815-009-9346-2
Tuscher JJ, Day JJ (2019) Multigenerational epigenetic inheritance: One step forward, two generations back. Neurobiol Dis 132:104591. https://doi.org/10.1016/j.nbd.2019.104591
van Otterdijk SD, Michels KB (2016) Transgenerational epigenetic inheritance in mammals: how good is the evidence? FASEB J 30(7):2457–2465. https://doi.org/10.1096/fj.201500083
van Cauwenbergh O, Di Serafino A, Tytgat J, Soubry A (2020) Transgenerational epigenetic effects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals. Clin Epigenet 12:65. https://doi.org/10.1186/s13148-020-00845-1
van de Werken C, van der Heijden GW, Eleveld C, Teeuwssen M, Albert M, Baarends WM, Laven JS, Peters AH, Baart EB (2014) Paternal heterochromatin formation in human embryos is H3K9/HP1 directed and primed by sperm-derived histone modifications. Nat Commun 5:5868. https://doi.org/10.1038/ncomms6868
Waterland RA, Kellermayer R, Laritsky E, Rayco-Solon P, Harris RA, Travisano M, Zhang W, Torskaya MS, Zhang J, Shen L, Manary MJ, Prentice AM (2010) Season of conception in rural Gambia affects DNA methylation at putative human metastable epialleles. PLoS Genet 6(12):e1001252. https://doi.org/10.1371/journal.pgen.1001252
Watson PJ, Fairall L, Schwabe JW (2012) Nuclear hormone receptor co-repressors: structure and function. Mol Cell Endocrinol 348:440–449. https://doi.org/10.1016/j.mce.2011.08.033
Weng YI, Hsu PY, Liyanarachchi S, Liu J, Deatherage DE, Huang YW, Zuo T, Rodriguez B, Lin CH, Cheng AL, Huang TH (2010) Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol 248(2):111–121. https://doi.org/10.1016/j.taap.2010.07.014
Wise RA (2004) Dopamine, learning and motivation. Nat Rev Neurosci 5(6):483–494. https://doi.org/10.1038/nrn1406
Woodhouse RM, Buchmann G, Hoe M, Harney DJ, Low JKK, Larance M, Boag PR, Ashe A (2018) Chromatin modifiers SET-25 and SET-32 are required for establishment but not long-term maintenance of transgenerational epigenetic inheritance. Cell Rep 25(8):2259-2272.e5. https://doi.org/10.1016/j.celrep.2018
Xu H, Wang F, Liu Y, Yu Y, Gelernter J, Zhang H (2014) Sex-biased methylome and transcriptome in human prefrontal cortex. Hum Mol Genet 23(5):1260–1270. https://doi.org/10.1093/hmg/ddt516
Yehuda R, Daskalakis NP, Lehrner A, Desarnaud F, Bader HN, Makotkine I, Flory JD, Bierer LM, Meaney MJ (2014) Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring. Am J Psychiatry 171(8):872–880. https://doi.org/10.1176/appi.ajp.2014.13121571
Yehuda R, Daskalakis NP, Bierer LM, Bader HN, Klengel T, Holsboer F, Binder EB (2016) Holocaust exposure induced intergenerational effects on FKBP5 methylation. Biol Psychiatry 80(5):372–380. https://doi.org/10.1016/j.biopsych.2015.08.005
Youngson NA, Lecomte V, Maloney CA, Leung P, Liu J, Hesson LB, Luciani F, Krause L, Morris MJ (2016) Obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring. Asian J Androl 18(6):930–936. https://doi.org/10.4103/1008-682X.163190
Yousefi P, Huen K, Davé V, Barcellos L, Eskenazi B, Holland N (2015) Sex differences in DNA methylation assessed by 450 K BeadChip in newborns. BMC Genom 16:911. https://doi.org/10.1186/s12864-015-2034-y
Yu R, Wang X, Moazed D (2018) Epigenetic inheritance mediated by coupling of RNAi and histone H3K9 methylation. Nature 558(7711):615–619. https://doi.org/10.1038/s41586-018-0239-3
Yuan S, Schuster A, Tang C, Yu T, Ortogero N, Bao J, Zheng H, Yan W (2016) Sperm-borne miRNAs and endo- siRNAs are important for fertilization and preimplantation embryonic development. Development 143:635–647. https://doi.org/10.1242/dev.131755
Zhang X, Wallace AD, Du P, Kibbe WA, Jafari N, Xie H, Lin S, Baccarelli A, Soares MB, Hou L (2012) DNA methylation alterations in response to pesticide exposure in vitro. Environ Mol Mutagen 53(7):542–549. https://doi.org/10.1002/em.21718
Zheng Y, Hlady RA, Joyce BT, Robertson KD, He C, Nannini DR, Kibbe WA, Achenbach CJ, Murphy RL, Roberts LR, Hou L (2019) DNA methylation of individual repetitive elements in hepatitis C virus infection- induced hepatocellular carcinoma. Clin Epigenetics 11(1):145. https://doi.org/10.1186/s13148-019-0733-y
Zhou Z, Lin Z, Pang X, Tariq MA, Ao X, Li P, Wang J (2017) Epigenetic regulation of long non-coding RNAs in gastric cancer. Oncotarget 9(27):19443–19458. https://doi.org/10.18632/oncotarget.23821
Funding
No funds, grants or other support was received.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ghai, M., Kader, F. A Review on Epigenetic Inheritance of Experiences in Humans. Biochem Genet 60, 1107–1140 (2022). https://doi.org/10.1007/s10528-021-10155-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10528-021-10155-7