{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:06:07Z","timestamp":1792037167438,"version":"4.4.0"},"reference-count":83,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T00:00:00Z","timestamp":1465862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T00:00:00Z","timestamp":1465862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent studies have suggested that physiological and behavioral traits may be transgenerationally inherited through the paternal lineage, possibly via non-genomic signals derived from the sperm. To investigate how paternal stress might influence offspring behavioral phenotypes, a model of hypothalamic\u2013pituitary\u2013adrenal (HPA) axis dysregulation was used. Male breeders were administered water supplemented with corticosterone (CORT) for 4 weeks before mating with untreated female mice. Female, but not male, F1 offspring of CORT-treated fathers displayed altered fear extinction at 2 weeks of age. Only male F1 offspring exhibited altered patterns of ultrasonic vocalization at postnatal day 3 and, as adults, showed decreased time in open on the elevated-plus maze and time in light on the light\u2013dark apparatus, suggesting a hyperanxiety-like behavioral phenotype due to paternal CORT treatment. Interestingly, expression of the paternally imprinted gene <jats:italic>Igf2<\/jats:italic> was increased in the hippocampus of F1 male offspring but downregulated in female offspring. Male and female F2 offspring displayed increased time spent in the open arm of the elevated-plus maze, suggesting lower levels of anxiety compared with control animals. Only male F2 offspring showed increased immobility time on the forced-swim test and increased latency to feed on the novelty-supressed feeding test, suggesting a depression-like phenotype in these animals. Collectively, these data provide evidence that paternal CORT treatment alters anxiety and depression-related behaviors across multiple generations. Analysis of the small RNA profile in sperm from CORT-treated males revealed marked effects on the expression of small noncoding RNAs. Sperm from CORT-treated males contained elevated levels of three microRNAs, miR-98, miR-144 and miR-190b, which are predicted to interact with multiple growth factors, including <jats:italic>Igf2<\/jats:italic> and <jats:italic>Bdnf<\/jats:italic>. Sustained elevation of glucocorticoids is therefore involved in the transmission of paternal stress-induced traits across generations in a process involving small noncoding RNA signals transmitted by the male germline.<\/jats:p>","DOI":"10.1038\/tp.2016.109","type":"journal-article","created":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T13:44:35Z","timestamp":1465911875000},"page":"e837-e837","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":233,"title":["Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring"],"prefix":"10.1038","volume":"6","author":[{"given":"A K","family":"Short","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K A","family":"Fennell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V M","family":"Perreau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M K","family":"O\u2019Bryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J H","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T W","family":"Bredy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T Y","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J","family":"Hannan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,14]]},"reference":[{"key":"BFtp2016109_CR1","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1001\/archpsyc.64.9.1040","volume":"64","author":"R Yehuda","year":"2007","unstructured":"Yehuda R, Teicher MH, Seckl JR, Grossman RA, Morris A, Bierer LM . Parental posttraumatic stress disorder as a vulnerability factor for low cortisol trait in offspring of holocaust survivors. Arch Gen Psychiatry 2007; 64: 1040\u20131048.","journal-title":"Arch Gen Psychiatry"},{"key":"BFtp2016109_CR2","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/S0022-3956(01)00032-2","volume":"35","author":"R Yehuda","year":"2001","unstructured":"Yehuda R, Halligan SL, Bierer LM . Relationship of parental trauma exposure and PTSD to PTSD, depressive and anxiety disorders in offspring. J Psychiatr Res 2001; 35: 261\u2013270.","journal-title":"J Psychiatr Res"},{"key":"BFtp2016109_CR3","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1097\/00005053-198606000-00001","volume":"174","author":"R Rosenheck","year":"1986","unstructured":"Rosenheck R . Impact of posttraumatic stress disorder of World War II on the next generation. J Nerv Ment Dis 1986; 174: 319\u2013327.","journal-title":"J Nerv Ment Dis"},{"key":"BFtp2016109_CR4","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/S0079-6123(07)67009-5","volume":"167","author":"R Yehuda","year":"2007","unstructured":"Yehuda R, Bierer LM . Transgenerational transmission of cortisol and PTSD risk. Prog Brain Res 2007; 167: 121\u2013135.","journal-title":"Prog Brain Res"},{"key":"BFtp2016109_CR5","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.biopsych.2010.05.036","volume":"68","author":"TB Franklin","year":"2010","unstructured":"Franklin TB, Russig H, Weiss IC, Graff J, Linder N, Michalon A et al. Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry 2010; 68: 408\u2013415.","journal-title":"Biol Psychiatry"},{"key":"BFtp2016109_CR6","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.biopsych.2011.05.005","volume":"70","author":"DM Dietz","year":"2011","unstructured":"Dietz DM, Laplant Q, Watts EL, Hodes GE, Russo SJ, Feng J et al. Paternal transmission of stress-induced pathologies. Biol Psychiatry 2011; 70: 408\u2013414.","journal-title":"Biol Psychiatry"},{"key":"BFtp2016109_CR7","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.bbr.2004.05.013","volume":"156","author":"A Gregus","year":"2005","unstructured":"Gregus A, Wintink AJ, Davis AC, Kalynchuk LE . Effect of repeated corticosterone injections and restraint stress on anxiety and depression-like behavior in male rats. Behav Brain Res 2005; 156: 105\u2013114.","journal-title":"Behav Brain Res"},{"key":"BFtp2016109_CR8","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1002\/(SICI)1099-1700(199707)13:3<173::AID-SMI739>3.0.CO;2-6","volume":"13","author":"D Wheatley","year":"1997","unstructured":"Wheatley D . Stress, anxiety and depression. Stress Med 1997; 13: 173\u2013177.","journal-title":"Stress Med"},{"key":"BFtp2016109_CR9","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1093\/oxfordjournals.bmb.a011570","volume":"52","author":"S Checkley","year":"1996","unstructured":"Checkley S . The neuroendocrinology of depression and chronic stress. Br Med Bull 1996; 52: 597\u2013617.","journal-title":"Br Med Bull"},{"key":"BFtp2016109_CR10","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1016\/j.biopsych.2008.06.016","volume":"64","author":"SL Gourley","year":"2008","unstructured":"Gourley SL, Kiraly DD, Howell JL, Olausson P, Taylor JR . Acute hippocampal BDNF restores motivational and forced swim performance after corticosterone. Biol Psychiatry 2008; 64: 884\u2013890.","journal-title":"Biol Psychiatry"},{"key":"BFtp2016109_CR11","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1038\/npp.2008.123","volume":"34","author":"SL Gourley","year":"2009","unstructured":"Gourley SL, Kedves AT, Olausson P, Taylor JR . A history of corticosterone exposure regulates fear extinction and cortical NR2B, GluR2\/3, and BDNF. Neuropsychopharmacology 2009; 34: 707\u2013716.","journal-title":"Neuropsychopharmacology"},{"key":"BFtp2016109_CR12","first-page":"311","volume":"208","author":"C Osterlund","year":"2011","unstructured":"Osterlund C, Spencer RL . Corticosterone pretreatment suppresses stress-induced hypothalamic-pituitary-adrenal axis activity via multiple actions that vary with time, site of action, and de novo protein synthesis. J Endocrinol 2011; 208: 311\u2013322.","journal-title":"J Endocrinol"},{"key":"BFtp2016109_CR13","first-page":"32","volume":"9","author":"SL Gourley","year":"2009","unstructured":"Gourley SL, Taylor JR . Recapitulation and reversal of a persistent depression-like syndrome in rodents. Curr Protoc Neurosci 2009; 9: 32.","journal-title":"Curr Protoc Neurosci"},{"key":"BFtp2016109_CR14","doi-asserted-by":"publisher","first-page":"9003","DOI":"10.1523\/JNEUROSCI.0914-13.2013","volume":"33","author":"AB Rodgers","year":"2013","unstructured":"Rodgers AB, Morgan CP, Bronson SL, Revello S, Bale TL . Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. J Neurosci 2013; 33: 9003\u20139012.","journal-title":"J Neurosci"},{"key":"BFtp2016109_CR15","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1046\/j.1365-2826.1999.00288.x","volume":"11","author":"I Liberzon","year":"1999","unstructured":"Liberzon I, L\u00f3pez JF, Flagel SB, V\u00e1zquez DM, Young EA . Differential regulation of hippocampal glucocorticoid receptors mRNA and fast feedback: Relevance to post-traumatic stress disorder. J Neuroendocrinol 1999; 11: 11\u201317.","journal-title":"J Neuroendocrinol"},{"key":"BFtp2016109_CR16","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.pnpbp.2012.05.018","volume":"39","author":"S Chiba","year":"2012","unstructured":"Chiba S, Numakawa T, Ninomiya M, Richards MC, Wakabayashi C, Kunugi H . Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex. Prog Neuro-Psychopharmacology Biol Psychiatry 2012; 39: 112\u2013119.","journal-title":"Prog Neuro-Psychopharmacology Biol Psychiatry"},{"key":"BFtp2016109_CR17","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/0006-3223(93)90252-9","volume":"34","author":"R Yehuda","year":"1993","unstructured":"Yehuda R, Boisoneau D, Mason JW, Giller EL . Glucocorticoid receptor number and cortisol excretion in mood, anxiety, and psychotic disorders. Biol Psychiatry 1993; 34: 18\u201325.","journal-title":"Biol Psychiatry"},{"key":"BFtp2016109_CR18","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1038\/nn1971","volume":"10","author":"K Martinowich","year":"2007","unstructured":"Martinowich K, Manji H, Lu B . New insights into BDNF function in depression and anxiety. Nat Neurosci 2007; 10: 1089\u20131093.","journal-title":"Nat Neurosci"},{"key":"BFtp2016109_CR19","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1002\/jnr.21139","volume":"85","author":"T Aid","year":"2007","unstructured":"Aid T, Kazantseva A, Piirsoo M, Palm K, Timmusk T . Mouse and rat BDNF gene structure and expression revisited. J Neurosci Res 2007; 85: 525\u2013535.","journal-title":"J Neurosci Res"},{"key":"BFtp2016109_CR20","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/0896-6273(93)90335-O","volume":"10","author":"T Timmusk","year":"1993","unstructured":"Timmusk T, Palm K, Metsis M, Reintam T, Paalme V, Saarma M et al. Multiple promoters direct tissue-specific expression of the rat BDNF gene. Neuron 1993; 10: 475\u2013489.","journal-title":"Neuron"},{"key":"BFtp2016109_CR21","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1038\/sj.npp.1300703","volume":"30","author":"X Jiang","year":"2005","unstructured":"Jiang X, Xu K, Hoberman J, Tian F, Marko AJ, Waheed JF et al. BDNF variation and mood disorders: a novel functional promoter polymorphism and Val66Met are associated with anxiety but have opposing effects. Neuropsychopharmacology 2005; 30: 1353\u20131361.","journal-title":"Neuropsychopharmacology"},{"key":"BFtp2016109_CR22","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1126\/science.1129663","volume":"314","author":"Z-Y Chen","year":"2006","unstructured":"Chen Z-Y, Jing D, Bath KG, Ieraci A, Khan T, Siao C-J et al. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 2006; 314: 140\u2013143.","journal-title":"Science"},{"key":"BFtp2016109_CR23","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1101\/lm.029520.112","volume":"20","author":"D Baker-Andresen","year":"2013","unstructured":"Baker-Andresen D, Flavell CR, Li X, Bredy TW . Activation of BDNF signaling prevents the return of fear in female mice. Learn Mem 2013; 20: 237\u2013240.","journal-title":"Learn Mem"},{"key":"BFtp2016109_CR24","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1101\/lm.500907","volume":"14","author":"TW Bredy","year":"2007","unstructured":"Bredy TW, Wu H, Crego C, Zellhoefer J, Sun YE, Barad M . Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear. Learn Mem 2007; 14: 268\u2013276.","journal-title":"Learn Mem"},{"key":"BFtp2016109_CR25","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1159\/000090843","volume":"113","author":"FM Smith","year":"2006","unstructured":"Smith FM, Garfield AS, Ward A . Regulation of growth and metabolism by imprinted genes. Cytogenet Genome Res 2006; 113: 279\u2013291.","journal-title":"Cytogenet Genome Res"},{"key":"BFtp2016109_CR26","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.15252\/emmm.201404228","volume":"6","author":"M Pascual-Lucas","year":"2014","unstructured":"Pascual-Lucas M, Viana da Silva S, Di Scala M, Garcia-Barroso C, Gonz\u00e1lez-Aseguinolaza G, Mulle C et al. Insulin-like growth factor 2 reverses memory and synaptic deficits in APP transgenic mice. EMBO Mol Med 2014; 6: 1246\u20131262.","journal-title":"EMBO Mol Med"},{"key":"BFtp2016109_CR27","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1038\/mp.2009.15","volume":"14","author":"J-M Revest","year":"2009","unstructured":"Revest J-M, Dupret D, Koehl M, Funk-Reiter C, Grosjean N, Piazza P-V et al. Adult hippocampal neurogenesis is involved in anxiety-related behaviors. Mol Psychiatry 2009; 14: 959\u2013967.","journal-title":"Mol Psychiatry"},{"key":"BFtp2016109_CR28","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1111\/gbb.12249","volume":"14","author":"EB Vangeel","year":"2015","unstructured":"Vangeel EB, Izzi B, Hompes T, Vansteelandt K, Lambrechts D, Freson K et al. DNA methylation in imprinted genes IGF2 and GNASXL is associated with prenatal maternal stress. Genes Brain Behav 2015; 14: 573\u2013582.","journal-title":"Genes Brain Behav"},{"key":"BFtp2016109_CR29","doi-asserted-by":"publisher","first-page":"2311","DOI":"10.1038\/ncomms3311","volume":"4","author":"MA Mikaelsson","year":"2013","unstructured":"Mikaelsson MA, Const\u00e2ncia M, Dent CL, Wilkinson LS, Humby T . Placental programming of anxiety in adulthood revealed by Igf2-null models. Nat Commun 2013; 4: 2311.","journal-title":"Nat Commun"},{"key":"BFtp2016109_CR30","doi-asserted-by":"publisher","first-page":"4071","DOI":"10.1038\/emboj.2011.293","volume":"30","author":"RC Agis-Balboa","year":"2011","unstructured":"Agis-Balboa RC, Arcos-Diaz D, Wittnam J, Govindarajan N, Blom K, Burkhardt S et al. A hippocampal insulin-growth factor 2 pathway regulates the extinction of fear memories. EMBO J 2011; 30: 4071\u20134083.","journal-title":"EMBO J"},{"key":"BFtp2016109_CR31","doi-asserted-by":"publisher","first-page":"e19218","DOI":"10.1371\/journal.pone.0019218","volume":"6","author":"S Chourbaji","year":"2011","unstructured":"Chourbaji S, Hoyer C, Richter SH, Brandwein C, Pfeiffer N, Vogt MA et al. Differences in mouse maternal care behavior - is there a genetic impact of the glucocorticoid receptor? PLoS One 2011; 6: e19218\u2013e19218.","journal-title":"PLoS One"},{"key":"BFtp2016109_CR32","doi-asserted-by":"publisher","first-page":"e3067","DOI":"10.1371\/journal.pone.0003067","volume":"3","author":"ML Scattoni","year":"2008","unstructured":"Scattoni ML, Gandhy SU, Ricceri L, Crawley JN . Unusual repertoire of vocalizations in the BTBR T+tf\/J mouse model of autism. PLoS One 2008; 3: e3067\u2013e3067.","journal-title":"PLoS One"},{"key":"BFtp2016109_CR33","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3389\/fphar.2013.00093","volume":"4","author":"TY Pang","year":"2013","unstructured":"Pang TY, Du X, Catchlove WA, Renoir T, Lawrence AJ, Hannan AJ . Positive environmental modification of depressive phenotype and abnormal hypothalamic-pituitary-adrenal axis activity in female C57BL\/6\u2009J mice during abstinence from chronic ethanol consumption. Front Pharmacol 2013; 4: 93.","journal-title":"Front Pharmacol"},{"key":"BFtp2016109_CR34","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1093\/hmg\/ddn385","volume":"18","author":"TYC Pang","year":"2009","unstructured":"Pang TYC, Du X, Zajac MS, Howard ML, Hannan AJ . Altered serotonin receptor expression is associated with depression-related behavior in the R6\/1 transgenic mouse model of Huntington\u2019s disease. Hum Mol Genet 2009; 18: 753\u2013766.","journal-title":"Hum Mol Genet"},{"key":"BFtp2016109_CR35","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/S0006-3223(02)01507-X","volume":"52","author":"M Davis","year":"2002","unstructured":"Davis M, Myers KM . The role of glutamate and gamma-aminobutyric acid in fear extinction\u202f: clinical implications for exposure therapy. Biol Psychiatry 2002; 52: 998\u20131007.","journal-title":"Biol Psychiatry"},{"key":"BFtp2016109_CR36","doi-asserted-by":"publisher","first-page":"10802","DOI":"10.1523\/JNEUROSCI.0596-09.2009","volume":"29","author":"JH Kim","year":"2009","unstructured":"Kim JH, Hamlin AS, Richardson R . Fear extinction across development: the involvement of the medial prefrontal cortex as assessed by temporary inactivation and immunohistochemistry. J Neurosci 2009; 29: 10802\u201310808.","journal-title":"J Neurosci"},{"key":"BFtp2016109_CR37","doi-asserted-by":"publisher","first-page":"182","DOI":"10.3928\/0048-5713-19880301-11","volume":"18","author":"MDRK Pitman","year":"1988","unstructured":"Pitman MDRK . Post-traumatic stress disorder, conditioning, and network theory. Psychiatr Ann 1988; 18: 182\u2013184 187\u2013189.","journal-title":"Psychiatr Ann"},{"key":"BFtp2016109_CR38","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1037\/0021-843X.109.2.290","volume":"109","author":"SP Orr","year":"2000","unstructured":"Orr SP, Metzger LJ, Lasko NB, Macklin ML, Peri T, Pitman RK . De novo conditioning in trauma-exposed individuals with and without posttraumatic stress disorder. J Abnorm Psychol 2000; 109: 290\u2013298.","journal-title":"J Abnorm Psychol"},{"key":"BFtp2016109_CR39","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.neuroscience.2004.08.018","volume":"129","author":"J Debiec","year":"2004","unstructured":"Debiec J, Ledoux JE . Disruption of reconsolidation but not consolidation of auditory fear conditioning by noradrenergic blockade in the amygdala. Neuroscience 2004; 129: 267\u2013272.","journal-title":"Neuroscience"},{"key":"BFtp2016109_CR40","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1016\/j.brat.2007.02.012","volume":"45","author":"J Blechert","year":"2007","unstructured":"Blechert J, Michael T, Vriends N, Margraf J, Wilhelm FH . Fear conditioning in posttraumatic stress disorder: evidence for delayed extinction of autonomic, experiential, and behavioural responses. Behav Res Ther 2007; 45: 2019\u20132033.","journal-title":"Behav Res Ther"},{"key":"BFtp2016109_CR41","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1196\/annals.1301.012","volume":"1008","author":"BO Rothbaum","year":"2003","unstructured":"Rothbaum BO, Davis M . Applying learning principles to the treatment of post-trauma reactions. Ann N Y Acad Sci 2003; 1008: 112\u2013121.","journal-title":"Ann N Y Acad Sci"},{"key":"BFtp2016109_CR42","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1037\/1528-3542.5.1.103","volume":"5","author":"T Michael","year":"2005","unstructured":"Michael T, Ehlers A, Halligan SL . Enhanced priming for trauma-related material in posttraumatic stress disorder. Emotion 2005; 5: 103\u2013112.","journal-title":"Emotion"},{"key":"BFtp2016109_CR43","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.nlm.2007.03.004","volume":"88","author":"JH Kim","year":"2007","unstructured":"Kim JH, Richardson R . A developmental dissociation in reinstatement of an extinguished fear response in rats. Neurobiol Learn Mem 2007; 88: 48\u201357.","journal-title":"Neurobiol Learn Mem"},{"key":"BFtp2016109_CR44","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1126\/science.1174146","volume":"325","author":"N Gogolla","year":"2009","unstructured":"Gogolla N, Caroni P, L\u00fcthi A, Herry C . Perineuronal nets protect fear memories from erasure. Science 2009; 325: 1258\u20131261.","journal-title":"Science"},{"key":"BFtp2016109_CR45","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1037\/a0022008","volume":"125","author":"BL Callaghan","year":"2011","unstructured":"Callaghan BL, Richardson R . Maternal separation results in early emergence of adult-like fear and extinction learning in infant rats. Behav Neurosci 2011; 125: 20\u201328.","journal-title":"Behav Neurosci"},{"key":"BFtp2016109_CR46","doi-asserted-by":"publisher","first-page":"e138","DOI":"10.1038\/tp.2012.65","volume":"2","author":"BL Callaghan","year":"2012","unstructured":"Callaghan BL, Richardson R . The effect of adverse rearing environments on persistent memories in young rats: removing the brakes on infant fear memories. Transl Psychiatry 2012; 2: e138.","journal-title":"Transl Psychiatry"},{"key":"BFtp2016109_CR47","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1017\/S1461145714000303","volume":"17","author":"CE Handford","year":"2014","unstructured":"Handford CE, Tan S, Lawrence AJ, Kim JH . The effect of the mGlu5 negative allosteric modulator MTEP and NMDA receptor partial agonist D-cycloserine on Pavlovian conditioned fear. Int J Neuropsychopharmacol 2014; 17: 1521\u20131532.","journal-title":"Int J Neuropsychopharmacol"},{"key":"BFtp2016109_CR48","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1093\/humupd\/dmp032","volume":"16","author":"CL Borg","year":"2009","unstructured":"Borg CL, Wolski KM, Gibbs GM, O\u2019Bryan MK . Phenotyping male infertility in the mouse: how to get the most out of a \u2018non-performer\u2019. Hum Reprod Update 2009; 16: 205\u2013224.","journal-title":"Hum Reprod Update"},{"key":"BFtp2016109_CR49","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1242\/jcs.02704","volume":"119","author":"L Cotton","year":"2006","unstructured":"Cotton L, Gibbs GM, Sanchez-Partida LG, Morrison JR, de Kretser DM, O\u2019Bryan MK . FGFR-1 signaling is involved in spermiogenesis and sperm capacitation. J Cell Sci 2006; 119: 75\u201384.","journal-title":"J Cell Sci"},{"key":"BFtp2016109_CR50","doi-asserted-by":"publisher","first-page":"7034","DOI":"10.1073\/pnas.1015935108","volume":"108","author":"GM Gibbs","year":"2011","unstructured":"Gibbs GM, Orta G, Reddy T, Koppers AJ, Mart\u00ednez-L\u00f3pez P, de la Vega-Beltr\u00e0n JL et al. Cysteine-rich secretory protein 4 is an inhibitor of transient receptor potential M8 with a role in establishing sperm function. Proc Natl Acad Sci USA 2011; 108: 7034\u20137039.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFtp2016109_CR51","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger AM, Lohse M, Usadel B . Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 2014; 30: 2114\u20132120.","journal-title":"Bioinformatics"},{"key":"BFtp2016109_CR52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nar\/gks1039","volume":"41","author":"Y Liao","year":"2013","unstructured":"Liao Y, Smyth GK, Shi W . The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote. Nucleic Acids Res 2013; 41: 1\u201317.","journal-title":"Nucleic Acids Res"},{"key":"BFtp2016109_CR53","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","volume":"30","author":"Y Liao","year":"2014","unstructured":"Liao Y, Smyth GK, Shi W . FeatureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 2014; 30: 923\u2013930.","journal-title":"Bioinformatics"},{"key":"BFtp2016109_CR54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/gb-2006-7-s1-s4","volume":"7","author":"J Harrow","year":"2006","unstructured":"Harrow J, Denoeud F, Frankish A, Reymond A, Chen C-K, Chrast J et al. GENCODE: producing a reference annotation for ENCODE. Genome Biol 2006; 7: 1\u20139.","journal-title":"Genome Biol"},{"key":"BFtp2016109_CR55","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson MD, McCarthy DJ, Smyth GK . edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010; 26: 139\u2013140.","journal-title":"Bioinformatics"},{"key":"BFtp2016109_CR56","doi-asserted-by":"publisher","first-page":"R25","DOI":"10.1186\/gb-2010-11-3-r25","volume":"11","author":"MD Robinson","year":"2010","unstructured":"Robinson MD, Oshlack A . A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol 2010; 11: R25.","journal-title":"Genome Biol"},{"key":"BFtp2016109_CR57","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1038\/nprot.2009.97","volume":"4","author":"S Durinck","year":"2009","unstructured":"Durinck S, Spellman PT, Birney E, Huber W . Mapping identifiers for the integration of genomic datasets with the R\/Bioconductor package biomaRt. Nat Protoc 2009; 4: 1184\u20131191.","journal-title":"Nat Protoc"},{"key":"BFtp2016109_CR58","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.jbi.2011.05.002","volume":"44","author":"H Dweep","year":"2011","unstructured":"Dweep H, Sticht C, Pandey P, Gretz N . miRWalk\u2014database: prediction of possible miRNA binding sites by \u2018walking\u2019 the genes of three genomes. J Biomed Inform 2011; 44: 839\u2013847.","journal-title":"J Biomed Inform"},{"key":"BFtp2016109_CR59","doi-asserted-by":"publisher","first-page":"5466","DOI":"10.1038\/ncomms6466","volume":"5","author":"K Gapp","year":"2014","unstructured":"Gapp K, Soldado-Magraner S, Alvarez-S\u00e1nchez M, Bohacek J, Vernaz G, Shu H et al. Early life stress in fathers improves behavioural flexibility in their offspring. Nat Commun 2014; 5: 5466.","journal-title":"Nat Commun"},{"key":"BFtp2016109_CR60","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/nn.3695","volume":"17","author":"K Gapp","year":"2014","unstructured":"Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P, Prados J et al. Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat Neurosci 2014; 17: 667\u2013669.","journal-title":"Nat Neurosci"},{"key":"BFtp2016109_CR61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nar\/gkn923","volume":"37","author":"DW Huang","year":"2009","unstructured":"Huang DW, Sherman BT, Lempicki RA . Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009; 37: 1\u201313.","journal-title":"Nucleic Acids Res"},{"key":"BFtp2016109_CR62","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","volume":"4","author":"DW Huang","year":"2009","unstructured":"Huang DW, Sherman BT, Lempicki RA . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4: 44\u201357.","journal-title":"Nat Protoc"},{"key":"BFtp2016109_CR63","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1016\/S0091-3057(02)00809-2","volume":"72","author":"A Dirks","year":"2002","unstructured":"Dirks A, Fish EW, Kikusui T, van der Gugten J, Groenink L, Olivier B et al. Effects of corticotropin-releasing hormone on distress vocalizations and locomotion in maternally separated mouse pups. Pharmacol Biochem Behav 2002; 72: 993\u2013999.","journal-title":"Pharmacol Biochem Behav"},{"key":"BFtp2016109_CR64","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/sj.ejhg.5201538","volume":"14","author":"ME Pembrey","year":"2006","unstructured":"Pembrey ME, Bygren LO, Kaati G, Edvinsson S, Northstone K, Sjostrom M et al. Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet 2006; 14: 159\u2013166.","journal-title":"Eur J Hum Genet"},{"key":"BFtp2016109_CR65","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1023\/A:1010241825519","volume":"49","author":"LO Bygren","year":"2001","unstructured":"Bygren LO, Kaati G, Edvinsson S . Longevity determined by paternal ancestors\u2019 nutrition during their slow growth period. Acta Biotheor 2001; 49: 53\u201359.","journal-title":"Acta Biotheor"},{"key":"BFtp2016109_CR66","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1210\/en.2009-1436","volume":"151","author":"IN Karatsoreos","year":"2010","unstructured":"Karatsoreos IN, Bhagat SM, Bowles NP, Weil ZM, Pfaff DW, McEwen BS . Endocrine and physiological changes in response to chronic corticosterone: a potential model of the metabolic syndrome in mouse. Endocrinology 2010; 151: 2117\u20132127.","journal-title":"Endocrinology"},{"key":"BFtp2016109_CR67","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.jad.2010.11.005","volume":"131","author":"Z Xu","year":"2011","unstructured":"Xu Z, Zhang Y, Hou B, Gao Y, Wu Y, Zhang C . Chronic corticosterone administration from adolescence through early adulthood attenuates depression-like behaviors in mice. J Affect Disord 2011; 131: 128\u2013135.","journal-title":"J Affect Disord"},{"key":"BFtp2016109_CR68","doi-asserted-by":"publisher","first-page":"13699","DOI":"10.1073\/pnas.1508347112","volume":"112","author":"AB Rodgers","year":"2015","unstructured":"Rodgers AB, Morgan CP, Leu NA, Bale TL . Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress. Proc Natl Acad Sci USA 2015; 112: 13699\u201313704.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFtp2016109_CR69","doi-asserted-by":"publisher","first-page":"e0135605","DOI":"10.1371\/journal.pone.0135605","volume":"10","author":"B Nixon","year":"2015","unstructured":"Nixon B, Stanger SJ, Mihalas BP, Reilly JN, Anderson AL, Dun MD et al. Next generation sequencing analysis reveals segmental patterns of microRNA expression in mouse epididymal epithelial cells. PLoS One 2015; 10: e0135605.","journal-title":"PLoS One"},{"key":"BFtp2016109_CR70","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1095\/biolreprod.115.132209","volume":"93","author":"B Nixon","year":"2015","unstructured":"Nixon B, Stanger SJ, Mihalas BP, Reilly JN, Anderson AL, Tyagi S et al. The microRNA signature of mouse spermatozoa is substantially modified during epididymal maturation. Biol Reprod 2015; 93: 91.","journal-title":"Biol Reprod"},{"key":"BFtp2016109_CR71","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1038\/nature09491","volume":"467","author":"SF Ng","year":"2010","unstructured":"Ng SF, Lin RC, Laybutt DR, Barres R, Owens JA, Morris MJ . Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature 2010; 467: 963\u2013966.","journal-title":"Nature"},{"key":"BFtp2016109_CR72","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1016\/j.cell.2010.12.008","volume":"143","author":"BR Carone","year":"2010","unstructured":"Carone BR, Fauquier L, Habib N, Shea JM, Hart CE, Li R et al. Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 2010; 143: 1084\u20131096.","journal-title":"Cell"},{"key":"BFtp2016109_CR73","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.neuroscience.2013.03.025","volume":"241","author":"R Mychasiuk","year":"2013","unstructured":"Mychasiuk R, Harker A, Ilnytskyy S, Gibb R . Paternal stress prior to conception alters DNA methylation and behaviour of developing rat offspring. Neuroscience 2013; 241: 100\u2013105.","journal-title":"Neuroscience"},{"key":"BFtp2016109_CR74","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1095\/biolreprod.113.115899","volume":"90","author":"S Petropoulos","year":"2014","unstructured":"Petropoulos S, Matthews SG, Szyf M . Adult glucocorticoid exposure leads to transcriptional and DNA methylation changes in nuclear steroid receptors in the hippocampus and kidney of mouse male offspring. Biol Reprod 2014; 90: 43.","journal-title":"Biol Reprod"},{"key":"BFtp2016109_CR75","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.devcel.2010.12.013","volume":"20","author":"AA Bazzini","year":"2011","unstructured":"Bazzini AA, Giraldez AJ . MicroRNAs sculpt gene expression in embryonic development: new insights from plants. Dev Cell 2011; 20: 3\u20134.","journal-title":"Dev Cell"},{"key":"BFtp2016109_CR76","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1093\/nar\/gkl096","volume":"34","author":"J Mineno","year":"2006","unstructured":"Mineno J, Okamoto S, Ando T, Sato M, Chono H, Izu H et al. The expression profile of microRNAs in mouse embryos. Nucleic Acids Res 2006; 34: 1765\u20131771.","journal-title":"Nucleic Acids Res"},{"key":"BFtp2016109_CR77","doi-asserted-by":"publisher","first-page":"10426","DOI":"10.1073\/pnas.1106141108","volume":"108","author":"SI Lee","year":"2011","unstructured":"Lee SI, Lee BR, Hwang YS, Lee HC, Rengaraj D, Song G et al. MicroRNA-mediated posttranscriptional regulation is required for maintaining undifferentiated properties of blastoderm and primordial germ cells in chickens. Proc Natl Acad Sci USA 2011; 108: 10426\u201310431.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFtp2016109_CR78","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1101\/lm.1877010","volume":"17","author":"A Kirtley","year":"2010","unstructured":"Kirtley A, Thomas KL . The exclusive induction of extinction is gated by BDNF. Learn Mem 2010; 17: 612\u2013619.","journal-title":"Learn Mem"},{"key":"BFtp2016109_CR79","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/j.neuropharm.2008.08.001","volume":"55","author":"T Deltheil","year":"2008","unstructured":"Deltheil T, Guiard BP, Cerdan J, David DJ, Tanaka KF, Rep\u00e9rant C et al. Behavioral and serotonergic consequences of decreasing or increasing hippocampus brain-derived neurotrophic factor protein levels in mice. Neuropharmacology 2008; 55: 1006\u20131014.","journal-title":"Neuropharmacology"},{"key":"BFtp2016109_CR80","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1038\/sj.mp.4001957","volume":"12","author":"SA Heldt","year":"2007","unstructured":"Heldt SA, Stanek L, Chhatwal JP, Ressler KJ . Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories. Mol Psychiatry 2007; 12: 656\u2013670.","journal-title":"Mol Psychiatry"},{"key":"BFtp2016109_CR81","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1016\/j.nbd.2012.03.015","volume":"46","author":"M Klug","year":"2012","unstructured":"Klug M, Hill RA, Choy KHC, Kyrios M, Hannan AJ, van den Buuse M . Long-term behavioral and NMDA receptor effects of young-adult corticosterone treatment in BDNF heterozygous mice. Neurobiol Dis 2012; 46: 722\u2013731.","journal-title":"Neurobiol Dis"},{"key":"BFtp2016109_CR82","doi-asserted-by":"publisher","first-page":"17046","DOI":"10.1073\/pnas.0806560105","volume":"105","author":"BT Heijmans","year":"2008","unstructured":"Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA 2008; 105: 17046\u201317049.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFtp2016109_CR83","doi-asserted-by":"publisher","first-page":"e442","DOI":"10.1371\/journal.pmed.0030442","volume":"3","author":"CD Mathers","year":"2006","unstructured":"Mathers CD, Loncar D . Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3: e442.","journal-title":"PLoS Med"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/tp2016109.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/tp2016109","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/tp2016109.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T08:38:58Z","timestamp":1672821538000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/tp2016109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,14]]},"references-count":83,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2016,6]]}},"alternative-id":["BFtp2016109"],"URL":"https:\/\/doi.org\/10.1038\/tp.2016.109","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,14]]},"assertion":[{"value":"24 March 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}