{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T11:14:29Z","timestamp":1769944469344,"version":"3.49.0"},"reference-count":104,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"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>Pre-reproductive stress (PRS) to adolescent female rats alters anxiogenic behavior in first (F1)- and second-generation (F2) offspring and increases mRNA expression of corticotropin-releasing factor receptor type 1 (<jats:italic>Crhr1)<\/jats:italic> in oocytes and in neonate offspring brain. Here, we ask whether the expression of <jats:italic>Crhr1<\/jats:italic> and <jats:italic>Crhr1-<\/jats:italic>targeting microRNA is altered in brain, blood, and oocytes of exposed females and in the brain of their neonate and adult F1 and F2 offspring. In addition, we inquire whether maternal post-stress drug treatment reverses PRS-induced abnormalities in offspring. We find that PRS induces a selective increase in <jats:italic>Crhr1-<\/jats:italic>targeting mir-34a and mir-34c in blood and oocytes, while non-<jats:italic>Crhr1<\/jats:italic> microRNA molecules remain unaltered. PRS induces similar microRNA changes in prefrontal cortex of F1 and F2 neonates. In adult animals, cortical <jats:italic>Crhr1<\/jats:italic>, but not mir-34, expression is affected by both maternal and direct stress exposure. Post-PRS fluoxetine (FLX) treatment increases pup mortality, and both FLX and the <jats:italic>Crhr1<\/jats:italic> antagonist NBI 27914 reverse some of the effects of PRS and also have independent effects on F1 behavior and gene expression. PRS also alters behavior as well as gene and miRNA expression patterns in paternally derived F2 offspring, producing effects that are different from those previously found in maternally derived F2 offspring. These findings extend current knowledge on inter- and trans-generational transfer of stress effects, point to microRNA changes in stress-exposed oocytes as a potential mechanism, and highlight the consequences of post-stress pharmacological interventions in adolescence.<\/jats:p>","DOI":"10.1038\/s41398-021-01220-1","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T12:22:33Z","timestamp":1612527753000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Pre-reproductive stress in adolescent female rats alters oocyte microRNA expression and offspring phenotypes: pharmacological interventions and putative mechanisms"],"prefix":"10.1038","volume":"11","author":[{"given":"Hiba","family":"Zaidan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalia","family":"Galiani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5082-0686","authenticated-orcid":false,"given":"Inna","family":"Gaisler-Salomon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"1220_CR1","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1177\/070674378803300309","volume":"33","author":"JJ Sigal","year":"1988","unstructured":"Sigal, J. J., DiNicola, V. F. & Buonvino, M. Grandchildren of survivors: can negative effects of prolonged exposure to excessive stress be observed two generations later? Can. J. Psychiatry 33, 207\u2013212 (1988).","journal-title":"Can. J. Psychiatry"},{"key":"1220_CR2","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/s10802-016-0153-9","volume":"45","author":"A Shachar-Dadon","year":"2017","unstructured":"Shachar-Dadon, A., Gueron-Sela, N., Weintraub, Z., Maayan-Metzger, A. & Leshem, M. Pre-conception war exposure and mother and child adjustment 4 years later. J. Abnorm. Child Psychol. 45, 131\u2013142 (2017).","journal-title":"J. Abnorm. Child Psychol."},{"key":"1220_CR3","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1016\/j.psyneuen.2009.10.009","volume":"35","author":"SR Brand","year":"2010","unstructured":"Brand, S. R. et al. The impact of maternal childhood abuse on maternal and infant HPA axis function in the postpartum period. Psychoneuroendocrinology 35, 686\u2013693 (2010).","journal-title":"Psychoneuroendocrinology"},{"key":"1220_CR4","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/S0079-6123(07)67009-5","volume":"167","author":"R Yehuda","year":"2008","unstructured":"Yehuda, R. & Bierer, L. M. Transgenerational transmission of cortisol and PTSD risk. Prog. Brain Res. 167, 121\u2013135 (2008).","journal-title":"Prog. Brain Res."},{"key":"1220_CR5","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.nbd.2009.11.012","volume":"39","author":"TB Franklin","year":"2010","unstructured":"Franklin, T. B. & Mansuy, I. M. Epigenetic inheritance in mammals: evidence for the impact of adverse environmental effects. Neurobiol. Dis. 39, 61\u201365 (2010).","journal-title":"Neurobiol. Dis."},{"key":"1220_CR6","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3389\/fnbeh.2011.00003","volume":"5","author":"IC Weiss","year":"2011","unstructured":"Weiss, I. C., Franklin, T. B., Vizi, S. & Mansuy, I. M. Inheritable effect of unpredictable maternal separation on behavioral responses in mice. Front Behav. Neurosci. 5, 3 (2011).","journal-title":"Front Behav. Neurosci."},{"key":"1220_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6466","volume":"5","author":"K Gapp","year":"2014","unstructured":"Gapp, K. et al. Early life stress in fathers improves behavioural flexibility in their offspring. Nat. Commun. 5, 5466 (2014).","journal-title":"Nat. Commun."},{"key":"1220_CR8","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.biopsych.2010.05.036","volume":"68","author":"TB Franklin","year":"2010","unstructured":"Franklin, T. B. et al. Epigenetic transmission of the impact of early stress across generations. Biol. Psychiatry 68, 408\u2013415 (2010).","journal-title":"Biol. Psychiatry"},{"key":"1220_CR9","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.biopsych.2012.06.035","volume":"73","author":"L Saavedra-Rodriguez","year":"2013","unstructured":"Saavedra-Rodriguez, L. & Feig, L. A. Chronic social instability induces anxiety and defective social interactions across generations. Biol. Psychiatry 73, 44\u201353 (2013).","journal-title":"Biol. Psychiatry"},{"key":"1220_CR10","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.biopsych.2011.05.005","volume":"70","author":"DM Dietz","year":"2011","unstructured":"Dietz, D. M. et al. Paternal transmission of stress-induced pathologies. Biol. Psychiatry 70, 408\u2013414 (2011).","journal-title":"Biol. Psychiatry"},{"key":"1220_CR11","doi-asserted-by":"crossref","first-page":"dvy023","DOI":"10.1093\/eep\/dvy023","volume":"4","author":"G van Steenwyk","year":"2018","unstructured":"van Steenwyk, G., Roszkowski, M., Manuella, F., Franklin, T. B. & Mansuy, I. M. Transgenerational inheritance of behavioral and metabolic effects of paternal exposure to traumatic stress in early postnatal life: evidence in the 4th generation. Environ. Epigenet 4, dvy023 (2018).","journal-title":"Environ. Epigenet"},{"key":"1220_CR12","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.neuroscience.2012.10.048","volume":"249","author":"L Eiland","year":"2013","unstructured":"Eiland, L. & Romeo, R. D. Stress and the developing adolescent brain. Neuroscience 249, 162\u2013171 (2013).","journal-title":"Neuroscience"},{"key":"1220_CR13","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/S0149-7634(00)00014-2","volume":"24","author":"LP Spear","year":"2000","unstructured":"Spear, L. P. The adolescent brain and age-related behavioral manifestations. Neurosci. Biobehav. Rev. 24, 417\u2013463 (2000).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"1220_CR14","doi-asserted-by":"publisher","first-page":"292","DOI":"10.3389\/fnmol.2018.00292","volume":"11","author":"I Lacal","year":"2018","unstructured":"Lacal, I. & Ventura, R. Epigenetic inheritance: concepts, mechanisms and perspectives. Front. Mol. Neurosci. 11, 292 (2018).","journal-title":"Front. Mol. Neurosci."},{"key":"1220_CR15","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.molmed.2014.12.004","volume":"21","author":"M Szyf","year":"2015","unstructured":"Szyf, M. Nongenetic inheritance and transgenerational epigenetics. Trends Mol. Med. 21, 134\u2013144 (2015).","journal-title":"Trends Mol. Med."},{"key":"1220_CR16","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/nrg3964","volume":"16","author":"J Bohacek","year":"2015","unstructured":"Bohacek, J. & Mansuy, I. M. Molecular insights into transgenerational non-genetic inheritance of acquired behaviours. Nat. Rev. Genet. 16, 641\u2013652 (2015).","journal-title":"Nat. Rev. Genet."},{"key":"1220_CR17","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1126\/science.286.5442.1155","volume":"286","author":"D Francis","year":"1999","unstructured":"Francis, D., Diorio, J., Liu, D. & Meaney, M. J. Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286, 1155\u20131158 (1999).","journal-title":"Science"},{"key":"1220_CR18","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/S0031-9384(03)00149-5","volume":"79","author":"FA Champagne","year":"2003","unstructured":"Champagne, F. A., Francis, D. D., Mar, A. & Meaney, M. J. Variations in maternal care in the rat as a mediating influence for the effects of environment on development. Physiol. Behav. 79, 359\u2013371 (2003).","journal-title":"Physiol. Behav."},{"key":"1220_CR19","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.yfrne.2015.11.001","volume":"40","author":"JP Curley","year":"2016","unstructured":"Curley, J. P. & Champagne, F. A. Influence of maternal care on the developing brain: Mechanisms, temporal dynamics and sensitive periods. Front Neuroendocrinol. 40, 52\u201366 (2016).","journal-title":"Front Neuroendocrinol."},{"key":"1220_CR20","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/nn.3695","volume":"17","author":"K Gapp","year":"2014","unstructured":"Gapp, K. et al. Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat. Neurosci. 17, 667\u2013669 (2014).","journal-title":"Nat. Neurosci."},{"key":"1220_CR21","doi-asserted-by":"publisher","first-page":"9003","DOI":"10.1523\/JNEUROSCI.0914-13.2013","volume":"33","author":"AB Rodgers","year":"2013","unstructured":"Rodgers, A. B., Morgan, C. P., Bronson, S. L., Revello, S. & Bale, T. L. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. J. Neurosci. 33, 9003\u20139012 (2013).","journal-title":"J. Neurosci."},{"key":"1220_CR22","doi-asserted-by":"publisher","first-page":"432","DOI":"10.4161\/epi.19794","volume":"7","author":"EL Marczylo","year":"2012","unstructured":"Marczylo, E. L., Amoako, A. A., Konje, J. C., Gant, T. W. & Marczylo, T. H. Smoking induces differential miRNA expression in human spermatozoa: a potential transgenerational epigenetic concern? Epigenetics 7, 432\u2013439 (2012).","journal-title":"Epigenetics"},{"key":"1220_CR23","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1016\/j.cell.2014.11.005","volume":"159","author":"A Ost","year":"2014","unstructured":"Ost, A. et al. Paternal diet defines offspring chromatin state and intergenerational obesity. Cell 159, 1352\u20131364 (2014).","journal-title":"Cell"},{"key":"1220_CR24","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1007\/s00128-012-0827-0","volume":"89","author":"Y Li","year":"2012","unstructured":"Li, Y., Li, M., Liu, Y., Song, G. & Liu, N. A microarray for microRNA profiling in spermatozoa from adult men living in an environmentally polluted site. Bull. Environ. contamination Toxicol. 89, 1111\u20131114 (2012).","journal-title":"Bull. Environ. contamination Toxicol."},{"key":"1220_CR25","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/nn.3594","volume":"17","author":"BG Dias","year":"2014","unstructured":"Dias, B. G. & Ressler, K. J. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat. Neurosci. 17, 89\u201396 (2014).","journal-title":"Nat. Neurosci."},{"key":"1220_CR26","doi-asserted-by":"publisher","first-page":"13699","DOI":"10.1073\/pnas.1508347112","volume":"112","author":"AB Rodgers","year":"2015","unstructured":"Rodgers, A. B., Morgan, C. P., Leu, N. A. & Bale, T. L. Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress. Proc. Natl Acad. Sci. USA 112, 13699\u201313704 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1220_CR27","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.semcdb.2015.07.003","volume":"43","author":"HJ Clarke","year":"2015","unstructured":"Clarke, H. J. & Vieux, K. F. Epigenetic inheritance through the female germ-line: the known, the unknown, and the possible. Semin. Cell Dev. Biol. 43, 106\u2013116 (2015).","journal-title":"Semin. Cell Dev. Biol."},{"key":"1220_CR28","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.psyneuen.2015.04.013","volume":"58","author":"H Zaidan","year":"2015","unstructured":"Zaidan, H. & Gaisler-Salomon, I. Prereproductive stress in adolescent female rats affects behavior and corticosterone levels in second-generation offspring. Psychoneuroendocrinology 58, 120\u2013129 (2015).","journal-title":"Psychoneuroendocrinology"},{"key":"1220_CR29","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.biopsych.2013.04.014","volume":"74","author":"H Zaidan","year":"2013","unstructured":"Zaidan, H., Leshem, M. & Gaisler-Salomon, I. Prereproductive stress to female rats alters corticotropin releasing factor type 1 expression in ova and behavior and brain corticotropin releasing factor type 1 expression in offspring. Biol. Psychiatry 74, 680\u2013687 (2013).","journal-title":"Biol. Psychiatry"},{"key":"1220_CR30","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1007\/s00429-014-0940-4","volume":"221","author":"J Bock","year":"2016","unstructured":"Bock, J. et al. Transgenerational sex-specific impact of preconception stress on the development of dendritic spines and dendritic length in the medial prefrontal cortex. Brain Struct. Funct. 221, 855\u2013863 (2016).","journal-title":"Brain Struct. Funct."},{"key":"1220_CR31","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1037\/a0014030","volume":"45","author":"A Shachar-Dadon","year":"2009","unstructured":"Shachar-Dadon, A., Schulkin, J. & Leshem, M. Adversity before conception will affect adult progeny in rats. Dev. Psychol. 45, 9\u201316 (2009).","journal-title":"Dev. Psychol."},{"key":"1220_CR32","doi-asserted-by":"publisher","first-page":"14191","DOI":"10.1523\/JNEUROSCI.1673-11.2011","volume":"31","author":"S Haramati","year":"2011","unstructured":"Haramati, S. et al. MicroRNA as repressors of stress-induced anxiety: the case of amygdalar miR-34. J. Neurosci. 31, 14191\u201314203 (2011).","journal-title":"J. Neurosci."},{"key":"1220_CR33","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.pneurobio.2016.06.005","volume":"143","author":"SL Hollins","year":"2016","unstructured":"Hollins, S. L. & Cairns, M. J. MicroRNA: small RNA mediators of the brains genomic response to environmental stress. Prog. Neurobiol. 143, 61\u201381 (2016).","journal-title":"Prog. Neurobiol."},{"key":"1220_CR34","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1007\/s12035-016-0365-6","volume":"55","author":"M Zhou","year":"2018","unstructured":"Zhou, M. et al. Abnormal expression of microRNAs induced by chronic unpredictable mild stress in rat hippocampal tissues. Mol. Neurobiol. 55, 917\u2013935 (2018).","journal-title":"Mol. Neurobiol."},{"key":"1220_CR35","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/j.biopsych.2018.01.009","volume":"83","author":"NP Daskalakis","year":"2018","unstructured":"Daskalakis, N. P., Provost, A. C., Hunter, R. G. & Guffanti, G. Noncoding RNAs: stress, glucocorticoids, and posttraumatic stress disorder. Biol. Psychiatry 83, 849\u2013865 (2018).","journal-title":"Biol. Psychiatry"},{"key":"1220_CR36","doi-asserted-by":"publisher","first-page":"901","DOI":"10.3892\/etm.2014.1504","volume":"7","author":"Y Cui","year":"2014","unstructured":"Cui, Y. et al. Differential expression of miRNA in rat myocardial tissues under psychological and physical stress. Exp. Ther. Med. 7, 901\u2013906 (2014).","journal-title":"Exp. Ther. Med."},{"key":"1220_CR37","doi-asserted-by":"publisher","first-page":"7401","DOI":"10.1007\/s12035-018-0925-z","volume":"55","author":"D Andolina","year":"2018","unstructured":"Andolina, D. et al. MicroRNA-34 contributes to the stress-related behavior and affects 5-HT prefrontal\/GABA amygdalar system through regulation of corticotropin-releasing factor receptor 1. Mol. Neurobiol. 55, 7401\u20137412 (2018).","journal-title":"Mol. Neurobiol."},{"key":"1220_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-016-0820-1","volume":"14","author":"BB Shenoda","year":"2016","unstructured":"Shenoda, B. B., Alexander, G. M. & Ajit, S. K. Hsa-miR-34a mediated repression of corticotrophin releasing hormone receptor 1 regulates pro-opiomelanocortin expression in patients with complex regional pain syndrome. J. Transl. Med. 14, 64 (2016).","journal-title":"J. Transl. Med."},{"key":"1220_CR39","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1016\/j.neuron.2014.07.019","volume":"83","author":"BG Dias","year":"2014","unstructured":"Dias, B. G. et al. Amygdala-dependent fear memory consolidation via miR-34a and Notch signaling. Neuron 83, 906\u2013918 (2014).","journal-title":"Neuron"},{"key":"1220_CR40","volume":"1","author":"SV Sotnikov","year":"2014","unstructured":"Sotnikov, S.V. & Markt, P.O. Epigenetic regulation of corticotropin-releasing hormone receptor 1: implication for anxiety-related disorders.Recep. Clin. Invest. 1, e175 (2014).","journal-title":"Recep. Clin. Invest."},{"key":"1220_CR41","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1002\/mrd.21005","volume":"76","author":"D Tesfaye","year":"2009","unstructured":"Tesfaye, D. et al. Identification and expression profiling of microRNAs during bovine oocyte maturation using heterologous approach. Mol. Reprod. Dev. 76, 665\u2013677 (2009).","journal-title":"Mol. Reprod. Dev."},{"key":"1220_CR42","doi-asserted-by":"publisher","first-page":"14270","DOI":"10.1523\/JNEUROSCI.5080-14.2015","volume":"35","author":"AK Rajbhandari","year":"2015","unstructured":"Rajbhandari, A. K., Baldo, B. A. & Bakshi, V. P. Predator Stress-Induced CRF Release Causes Enduring Sensitization of Basolateral Amygdala Norepinephrine Systems that Promote PTSD-Like Startle Abnormalities. J. Neurosci. 35, 14270\u201314285 (2015).","journal-title":"J. Neurosci."},{"key":"1220_CR43","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1016\/S0140-6736(04)16043-1","volume":"363","author":"CJ Whittington","year":"2004","unstructured":"Whittington, C. J. et al. Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet 363, 1341\u20131345 (2004).","journal-title":"Lancet"},{"key":"1220_CR44","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1097\/01.chi.0000183464.41777.c1","volume":"44","author":"DB Clark","year":"2005","unstructured":"Clark, D. B. et al. Fluoxetine for the treatment of childhood anxiety disorders: open-label, long-term extension to a controlled trial. J. Am. Acad. Child Adolesc. Psychiatry 44, 1263\u20131270 (2005).","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"1220_CR45","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.jsps.2015.03.006","volume":"24","author":"M Farhan","year":"2016","unstructured":"Farhan, M. & Haleem, D. J. Anxiolytic profile of fluoxetine as monitored following repeated administration in animal rat model of chronic mild stress. Saudi Pharm. J. 24, 571\u2013578 (2016).","journal-title":"Saudi Pharm. J."},{"key":"1220_CR46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0186700","volume":"12","author":"Y Lu","year":"2017","unstructured":"Lu, Y. et al. Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression. PLoS ONE 12, e0186700 (2017).","journal-title":"PLoS ONE"},{"key":"1220_CR47","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1002\/dev.20592","volume":"54","author":"M Leshem","year":"2012","unstructured":"Leshem, M. & Schulkin, J. Transgenerational effects of infantile adversity and enrichment in male and female rats. Dev. Psychobiol. 54, 169\u2013186 (2012).","journal-title":"Dev. Psychobiol."},{"key":"1220_CR48","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02071-x","volume":"7","author":"H Grossman","year":"2017","unstructured":"Grossman, H. et al. Regulation of GVBD in mouse oocytes by miR-125a-3p and Fyn kinase through modulation of actin filaments. Sci. Rep. 7, 2238 (2017).","journal-title":"Sci. Rep."},{"key":"1220_CR49","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-017-4409-8","volume":"19","author":"H Zaidan","year":"2018","unstructured":"Zaidan, H. et al. A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations. BMC Genomics 19, 28 (2018).","journal-title":"BMC Genomics"},{"key":"1220_CR50","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25, 402\u2013408 (2001).","journal-title":"Methods"},{"key":"1220_CR51","doi-asserted-by":"publisher","DOI":"10.1038\/srep36766","volume":"6","author":"M Isik","year":"2016","unstructured":"Isik, M., Blackwell, T. K. & Berezikov, E. MicroRNA mir-34 provides robustness to environmental stress response via the DAF-16 network in C. elegans. Sci. Rep. 6, 36766 (2016).","journal-title":"Sci. Rep."},{"key":"1220_CR52","doi-asserted-by":"publisher","first-page":"5658","DOI":"10.18632\/oncotarget.13923","volume":"8","author":"D Andolina","year":"2017","unstructured":"Andolina, D., Di Segni, M. & Ventura, R. MiRNA-34 and stress response. Oncotarget 8, 5658\u20135659 (2017).","journal-title":"Oncotarget"},{"key":"1220_CR53","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s00439-019-02046-0","volume":"139","author":"HE Kinser","year":"2020","unstructured":"Kinser, H. E. & Pincus, Z. MicroRNAs as modulators of longevity and the aging process. Hum. Genet. 139, 291\u2013308 (2020).","journal-title":"Hum. Genet."},{"key":"1220_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2017.82","volume":"7","author":"AK Short","year":"2017","unstructured":"Short, A. K. et al. Exercise alters mouse sperm small noncoding RNAs and induces a transgenerational modification of male offspring conditioned fear and anxiety. Transl. Psychiatry 7, e1114 (2017).","journal-title":"Transl. Psychiatry"},{"key":"1220_CR55","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/nature04674","volume":"441","author":"M Rassoulzadegan","year":"2006","unstructured":"Rassoulzadegan, M. et al. RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature 441, 469\u2013474 (2006).","journal-title":"Nature"},{"key":"1220_CR56","doi-asserted-by":"publisher","DOI":"10.1038\/srep09266","volume":"5","author":"S Yuan","year":"2015","unstructured":"Yuan, S., Oliver, D., Schuster, A., Zheng, H. & Yan, W. Breeding scheme and maternal small RNAs affect the efficiency of transgenerational inheritance of a paramutation in mice. Sci. Rep. 5, 9266 (2015).","journal-title":"Sci. Rep."},{"key":"1220_CR57","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12407","volume":"17","author":"K Gapp","year":"2018","unstructured":"Gapp, K. & Bohacek, J. Epigenetic germline inheritance in mammals: looking to the past to understand the future. Genes Brain Behav. 17, e12407 (2018).","journal-title":"Genes Brain Behav."},{"key":"1220_CR58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052331","volume":"7","author":"LM Wu","year":"2012","unstructured":"Wu, L. M. et al. Chronic unpredictable stress decreases expression of brain-derived neurotrophic factor (BDNF) in mouse ovaries: relationship to oocytes developmental potential. PLoS One 7, e52331 (2012).","journal-title":"PLoS One"},{"key":"1220_CR59","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1095\/biolreprod.110.087890","volume":"84","author":"SY Zhang","year":"2011","unstructured":"Zhang, S. Y. et al. Maternal restraint stress diminishes the developmental potential of oocytes. Biol. Reprod. 84, 672\u2013681 (2011).","journal-title":"Biol. Reprod."},{"key":"1220_CR60","doi-asserted-by":"publisher","DOI":"10.1038\/srep24036","volume":"6","author":"HJ Yuan","year":"2016","unstructured":"Yuan, H. J. et al. Glucocorticoids impair oocyte developmental potential by triggering apoptosis of ovarian cells via activating the Fas system. Sci. Rep. 6, 24036 (2016).","journal-title":"Sci. Rep."},{"key":"1220_CR61","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/nn.3603","volume":"17","author":"M Szyf","year":"2014","unstructured":"Szyf, M. Lamarck revisited: epigenetic inheritance of ancestral odor fear conditioning. Nat. Neurosci. 17, 2\u20134 (2014).","journal-title":"Nat. Neurosci."},{"key":"1220_CR62","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.gene.2014.01.051","volume":"538","author":"A Sharma","year":"2014","unstructured":"Sharma, A. Novel transcriptome data analysis implicates circulating microRNAs in epigenetic inheritance in mammals. Gene 538, 366\u2013372 (2014).","journal-title":"Gene"},{"key":"1220_CR63","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.schres.2010.07.002","volume":"124","author":"AH Kim","year":"2010","unstructured":"Kim, A. H. et al. MicroRNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders. Schizophrenia Res. 124, 183\u2013191 (2010).","journal-title":"Schizophrenia Res."},{"key":"1220_CR64","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.jpsychires.2014.03.008","volume":"54","author":"H-t Song","year":"2014","unstructured":"Song, H.-t et al. A preliminary analysis of association between the down-regulation of microRNA-181b expression and symptomatology improvement in schizophrenia patients before and after antipsychotic treatment. J. Psychiatr. Res. 54, 134\u2013140 (2014).","journal-title":"J. Psychiatr. Res."},{"key":"1220_CR65","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.brainres.2013.08.011","volume":"1533","author":"JS Truettner","year":"2013","unstructured":"Truettner, J. S., Motti, D. & Dietrich, W. D. MicroRNA overexpression increases cortical neuronal vulnerability to injury. Brain Res. 1533, 122\u2013130 (2013).","journal-title":"Brain Res."},{"key":"1220_CR66","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/mp.2014.163","volume":"20","author":"PW Gold","year":"2015","unstructured":"Gold, P. W. The organization of the stress system and its dysregulation in depressive illness. Mol. Psychiatry 20, 32\u201347 (2015).","journal-title":"Mol. Psychiatry"},{"key":"1220_CR67","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/j.neuron.2012.08.016","volume":"75","author":"TB Franklin","year":"2012","unstructured":"Franklin, T. B., Saab, B. J. & Mansuy, I. M. Neural mechanisms of stress resilience and vulnerability. Neuron 75, 747\u2013761 (2012).","journal-title":"Neuron"},{"key":"1220_CR68","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1037\/a0020608","volume":"3","author":"A Shrira","year":"2011","unstructured":"Shrira, A., Palgi, Y., Ben-Ezra, M. & Shmotkin, D. Transgenerational effects of trauma in midlife: evidence for resilience and vulnerability in offspring of Holocaust survivors. Psychol. Trauma. 3, 394\u2013402 (2011).","journal-title":"Psychol. Trauma."},{"key":"1220_CR69","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1159\/000363695","volume":"36","author":"S Jakob","year":"2014","unstructured":"Jakob, S. et al. Differential effects of prenatal stress in female 5-HTT-deficient mice: towards molecular mechanisms of resilience. Dev. Neurosci. 36, 454\u2013464 (2014).","journal-title":"Dev. Neurosci."},{"key":"1220_CR70","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.psyneuen.2017.01.021","volume":"78","author":"S Santarelli","year":"2017","unstructured":"Santarelli, S. et al. An adverse early life environment can enhance stress resilience in adulthood. Psychoneuroendocrinology 78, 213\u2013221 (2017).","journal-title":"Psychoneuroendocrinology"},{"key":"1220_CR71","doi-asserted-by":"publisher","first-page":"dvy021","DOI":"10.1093\/eep\/dvy021","volume":"4","author":"H Zaidan","year":"2018","unstructured":"Zaidan, H., Ramaswami, G., Barak, M., Li, J. B. & Gaisler-Salomon, I. Pre-reproductive stress and fluoxetine treatment in rats affect offspring A-to-I RNA editing, gene expression and social behavior. Environ. Epigenet. 4, dvy021 (2018).","journal-title":"Environ. Epigenet."},{"key":"1220_CR72","doi-asserted-by":"publisher","first-page":"2948","DOI":"10.1523\/JNEUROSCI.5289-06.2007","volume":"27","author":"GR Barker","year":"2007","unstructured":"Barker, G. R., Bird, F., Alexander, V. & Warburton, E. C. Recognition memory for objects, place, and temporal order: a disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex. J. Neurosci. 27, 2948\u20132957 (2007).","journal-title":"J. Neurosci."},{"key":"1220_CR73","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/S0306-4522(01)00291-3","volume":"106","author":"M Kabbaj","year":"2001","unstructured":"Kabbaj, M. & Akil, H. Individual differences in novelty-seeking behavior in rats: a c-fos study. Neuroscience 106, 535\u2013545 (2001).","journal-title":"Neuroscience"},{"key":"1220_CR74","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.physbeh.2007.01.017","volume":"91","author":"BR Mueller","year":"2007","unstructured":"Mueller, B. R. & Bale, T. L. Early prenatal stress impact on coping strategies and learning performance is sex dependent. Physiol. Behav. 91, 55\u201365 (2007).","journal-title":"Physiol. Behav."},{"key":"1220_CR75","doi-asserted-by":"publisher","first-page":"4999","DOI":"10.1210\/en.2009-0500","volume":"150","author":"GA Dunn","year":"2009","unstructured":"Dunn, G. A. & Bale, T. L. Maternal high-fat diet promotes body length increases and insulin insensitivity in second-generation mice. Endocrinology 150, 4999\u20135009 (2009).","journal-title":"Endocrinology"},{"key":"1220_CR76","doi-asserted-by":"publisher","first-page":"3202","DOI":"10.1210\/en.2004-1458","volume":"146","author":"S Chung","year":"2005","unstructured":"Chung, S. et al. Differential adaptive responses to chronic stress of maternally stressed male mice offspring. Endocrinology 146, 3202\u20133210 (2005).","journal-title":"Endocrinology"},{"key":"1220_CR77","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.bbr.2017.10.027","volume":"338","author":"L Chen","year":"2018","unstructured":"Chen, L. et al. Activation of CRF\/CRFR1 signaling in the basolateral nucleus of the amygdala contributes to chronic forced swim-induced depressive-like behaviors in rats. Behav. Brain Res. 338, 134\u2013142 (2018).","journal-title":"Behav. Brain Res."},{"key":"1220_CR78","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0006-8993(00)03277-7","volume":"893","author":"V Martinez","year":"2001","unstructured":"Martinez, V. & Tache, Y. Role of CRF receptor 1 in central CRF-induced stimulation of colonic propulsion in rats. Brain Res. 893, 29\u201335 (2001).","journal-title":"Brain Res."},{"key":"1220_CR79","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/S0029-7844(97)00070-7","volume":"89","author":"DJ Goldstein","year":"1997","unstructured":"Goldstein, D. J., Corbin, L. A. & Sundell, K. L. Effects of first-trimester fluoxetine exposure on the newborn. Obstet. Gynecol. 89, 713\u2013718 (1997).","journal-title":"Obstet. Gynecol."},{"key":"1220_CR80","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1258\/om.2009.090002","volume":"2","author":"A Freyer","year":"2009","unstructured":"Freyer, A. Drugs in Pregnancy and Lactation 8th Edition: A Reference Guide to Fetal and Neonatal Risk. Obstet. Med. 2, 89 (2009).","journal-title":"Obstet. Med."},{"key":"1220_CR81","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1159\/000106433","volume":"93","author":"DL Van den Hove","year":"2008","unstructured":"Van den Hove, D. L. et al. Prenatal maternal paroxetine treatment and neonatal mortality in the rat: a preliminary study. Neonatology 93, 52\u201355 (2008).","journal-title":"Neonatology"},{"key":"1220_CR82","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1006\/faat.1994.1098","volume":"23","author":"CV Vorhees","year":"1994","unstructured":"Vorhees, C. V. et al. A developmental neurotoxicity evaluation of the effects of prenatal exposure to fluoxetine in rats. Fundam. Appl Toxicol. 23, 194\u2013205 (1994).","journal-title":"Fundam. Appl Toxicol."},{"key":"1220_CR83","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000096645","volume":"79","author":"KL Bairy","year":"2007","unstructured":"Bairy, K. L., Madhyastha, S., Ashok, K. P., Bairy, I. & Malini, S. Developmental and behavioral consequences of prenatal fluoxetine. Pharmacology 79, 1\u201311 (2007).","journal-title":"Pharmacology"},{"key":"1220_CR84","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1111\/bcpt.12072","volume":"113","author":"JC Muller","year":"2013","unstructured":"Muller, J. C. et al. In utero and lactational exposure to fluoxetine in Wistar rats: pregnancy outcomes and sexual development. Basic Clin. Pharmacol. Toxicol. 113, 132\u2013140 (2013).","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"1220_CR85","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.reprotox.2018.02.004","volume":"77","author":"SM Hutchison","year":"2018","unstructured":"Hutchison, S. M., Masse, L. C., Pawluski, J. L. & Oberlander, T. F. Perinatal selective serotonin reuptake inhibitor (SSRI) effects on body weight at birth and beyond: A review of animal and human studies. Reprod. Toxicol. 77, 109\u2013121 (2018).","journal-title":"Reprod. Toxicol."},{"key":"1220_CR86","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.bbr.2017.01.043","volume":"323","author":"JC Schoeman","year":"2017","unstructured":"Schoeman, J. C., Steyn, S. F., Harvey, B. H. & Brink, C. B. Long-lasting effects of fluoxetine and\/or exercise augmentation on bio-behavioural markers of depression in pre-pubertal stress sensitive rats. Behav. Brain Res. 323, 86\u201399 (2017).","journal-title":"Behav. Brain Res."},{"key":"1220_CR87","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1097\/JCP.0b013e3181bf344c","volume":"29","author":"S Toh","year":"2009","unstructured":"Toh, S. et al. Antidepressant use during pregnancy and the risk of preterm delivery and fetal growth restriction. J. Clin. Psychopharmacol. 29, 555\u2013560 (2009).","journal-title":"J. Clin. Psychopharmacol."},{"key":"1220_CR88","doi-asserted-by":"publisher","DOI":"10.1038\/srep04873","volume":"4","author":"C Schmauss","year":"2014","unstructured":"Schmauss, C., Lee-McDermott, Z. & Medina, L. R. Trans-generational effects of early life stress: the role of maternal behavior. Sci. Rep. 4, 4873 (2014).","journal-title":"Sci. Rep."},{"key":"1220_CR89","doi-asserted-by":"publisher","first-page":"98837","DOI":"10.18632\/oncotarget.22007","volume":"8","author":"S Wei","year":"2017","unstructured":"Wei, S. et al. Impact of anger emotional stress before pregnancy on adult male offspring. Oncotarget 8, 98837\u201398852 (2017).","journal-title":"Oncotarget"},{"key":"1220_CR90","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1159\/000329417","volume":"88","author":"EK Sawyer","year":"2011","unstructured":"Sawyer, E. K. & Howell, L. L. Pharmacokinetics of fluoxetine in rhesus macaques following multiple routes of administration. Pharmacology 88, 44\u201349 (2011).","journal-title":"Pharmacology"},{"key":"1220_CR91","first-page":"98","volume":"288","author":"DK Raap","year":"1999","unstructured":"Raap, D. K. et al. Daily injections of fluoxetine induce dose-dependent desensitization of hypothalamic 5-HT1A receptors: reductions in neuroendocrine responses to 8-OH-DPAT and in levels of Gz and Gi proteins. J. Pharmacol. Exp. Ther. 288, 98\u2013106 (1999).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"1220_CR92","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.neuropharm.2013.11.011","volume":"79","author":"JY Lee","year":"2014","unstructured":"Lee, J. Y. et al. Fluoxetine inhibits transient global ischemia-induced hippocampal neuronal death and memory impairment by preventing blood\u2013brain barrier disruption. Neuropharmacology 79, 161\u2013171 (2014).","journal-title":"Neuropharmacology"},{"key":"1220_CR93","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/0166-2236(95)93942-Q","volume":"18","author":"N Barden","year":"1995","unstructured":"Barden, N., Reul, J. M. & Holsboer, F. Do antidepressants stabilize mood through actions on the hypothalamic-pituitary-adrenocortical system? Trends Neurosci. 18, 6\u201311 (1995).","journal-title":"Trends Neurosci."},{"key":"1220_CR94","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.bbr.2016.05.062","volume":"311","author":"AA Salari","year":"2016","unstructured":"Salari, A. A., Fatehi-Gharehlar, L., Motayagheni, N. & Homberg, J. R. Fluoxetine normalizes the effects of prenatal maternal stress on depression- and anxietylike behaviors in mouse dams and male offspring. Behav. Brain Res. 311, 354\u2013367 (2016).","journal-title":"Behav. Brain Res."},{"key":"1220_CR95","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.bbr.2016.09.021","volume":"317","author":"R Avitsur","year":"2017","unstructured":"Avitsur, R. Increased symptoms of illness following prenatal stress: Can it be prevented by fluoxetine? Behav. Brain Res. 317, 62\u201370 (2017).","journal-title":"Behav. Brain Res."},{"key":"1220_CR96","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1023\/A:1006986824213","volume":"19","author":"C Sanchez","year":"1999","unstructured":"Sanchez, C. & Hyttel, J. Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding. Cell. Mol. Neurobiol. 19, 467\u2013489 (1999).","journal-title":"Cell. Mol. Neurobiol."},{"key":"1220_CR97","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/aps.2017.83","volume":"39","author":"YH Ran","year":"2018","unstructured":"Ran, Y. H. et al. YL-0919, a dual 5-HT1A partial agonist and SSRI, produces antidepressant- and anxiolytic-like effects in rats subjected to chronic unpredictable stress. Acta pharmacologica Sin. 39, 12\u201323 (2018).","journal-title":"Acta pharmacologica Sin."},{"key":"1220_CR98","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.pbb.2016.12.007","volume":"153","author":"F Gomez","year":"2017","unstructured":"Gomez, F. & Garcia-Garcia, L. Anxiogenic-like effects of fluoxetine render adult male rats vulnerable to the effects of a novel stress. Pharmacol., Biochem., Behav. 153, 32\u201344 (2017).","journal-title":"Pharmacol., Biochem., Behav."},{"key":"1220_CR99","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1080\/10253890802309861","volume":"12","author":"CA Lowry","year":"2009","unstructured":"Lowry, C. A. et al. Fluoxetine inhibits corticotropin-releasing factor (CRF)-induced behavioural responses in rats. Stress 12, 225\u2013239 (2009).","journal-title":"Stress"},{"key":"1220_CR100","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.neuropharm.2017.10.009","volume":"128","author":"M Gemmel","year":"2018","unstructured":"Gemmel, M., Kokras, N., Dalla, C. & Pawluski, J. L. Perinatal fluoxetine prevents the effect of pre-gestational maternal stress on 5-HT in the PFC, but maternal stress has enduring effects on mPFC synaptic structure in offspring. Neuropharmacology 128, 168\u2013180 (2018).","journal-title":"Neuropharmacology"},{"key":"1220_CR101","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1016\/j.cub.2019.04.070","volume":"29","author":"V Ferretti","year":"2019","unstructured":"Ferretti, V. et al. Oxytocin signaling in the central amygdala modulates emotion discrimination in mice. Curr. Biol. 29, 1938\u20131953 (2019). e1936.","journal-title":"Curr. Biol."},{"key":"1220_CR102","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.neulet.2017.07.008","volume":"657","author":"PE Carneiro de Oliveira","year":"2017","unstructured":"Carneiro de Oliveira, P. E., Zaniboni, C. R., Carmona, I. M., Fonseca, A. R. & Canto-de-Souza, A. Preliminary behavioral assessment of cagemates living with conspecifics submitted to chronic restraint stress in mice. Neurosci. Lett. 657, 204\u2013210 (2017).","journal-title":"Neurosci. Lett."},{"key":"1220_CR103","doi-asserted-by":"publisher","first-page":"27","DOI":"10.3389\/neuro.08.027.2009","volume":"3","author":"A Korosi","year":"2009","unstructured":"Korosi, A. & Baram, T. Z. The pathways from mother\u2019s love to baby\u2019s future. Front. Behav. Neurosci. 3, 27 (2009).","journal-title":"Front. Behav. Neurosci."},{"key":"1220_CR104","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1146\/annurev.neuro.24.1.1161","volume":"24","author":"MJ Meaney","year":"2001","unstructured":"Meaney, M. J. Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu. Rev. Neurosci. 24, 1161\u20131192 (2001).","journal-title":"Annu. Rev. Neurosci."}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-021-01220-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-021-01220-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-021-01220-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T15:25:36Z","timestamp":1669821936000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-021-01220-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,5]]},"references-count":104,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["1220"],"URL":"https:\/\/doi.org\/10.1038\/s41398-021-01220-1","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,5]]},"assertion":[{"value":"16 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 December 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 January 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"113"}}