{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T02:25:18Z","timestamp":1789871118265,"version":"4.0.1"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071525"],"award-info":[{"award-number":["82071525"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571269"],"award-info":[{"award-number":["81571269"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In response to stressful events, the hypothalamic-pituitary-adrenal (HPA) axis is activated, and consequently glucocorticoids are released by the adrenal gland into the blood circulation. A large body of research has illustrated that excessive glucocorticoids in the hippocampus exerts negative feedback regulation of the HPA axis through glucocorticoid receptor (GR), which is critical for the homeostasis of the HPA axis. Maternal prenatal stress causes dysfunction of the HPA axis feedback mechanism in their offspring in adulthood. Here we report that telomerase reverse transcriptase (TERT) gene knockout causes hyperactivity of the HPA axis without hippocampal GR deficiency. We found that the level of TERT in the dentate gyrus (DG) of the hippocampus during the developmental stage determines the responses of the HPA axis to stressful events in adulthood through modulating the excitability of the dentate granular cells (DGCs) rather than the expression of GR. Our study also suggests that the prenatal high level of glucocorticoids exposure-induced hypomethylation at Chr13:73764526 in the first exon of mouse <jats:italic>Tert<\/jats:italic> gene accounted for TERT deficiency in the DG and HPA axis abnormality in the adult offspring. This study reveals a novel GR-independent mechanism underlying prenatal stress-associated HPA axis impairment, providing a new angle for understanding the mechanisms for maintaining HPA axis homeostasis.<\/jats:p>","DOI":"10.1038\/s41380-022-01898-9","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T13:06:14Z","timestamp":1670504774000},"page":"1383-1395","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Prenatal stress modulates HPA axis homeostasis of offspring through dentate TERT independently of glucocorticoids receptor"],"prefix":"10.1038","volume":"28","author":[{"given":"Meng-Ying","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Lu","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian-Hui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9933-8735","authenticated-orcid":false,"given":"Hua-Chen","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Hu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian-Di","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Wei","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ping","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Lin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3870-3070","authenticated-orcid":false,"given":"Qi-Gang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"1898_CR1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.neubiorev.2009.11.008.","volume":"35","author":"V Glover","year":"2010","unstructured":"Glover V, O\u2019Connor TG, O\u2019Donnell K. Prenatal stress and the programming of the HPA axis. Neurosci Biobehav Rev. 2010;35:17\u201322. https:\/\/doi.org\/10.1016\/j.neubiorev.2009.11.008.","journal-title":"Neurosci Biobehav Rev"},{"key":"1898_CR2","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1017\/S0954579418000342.","volume":"30","author":"BRH van den Bergh","year":"2018","unstructured":"van den Bergh BRH, Dahnke R, Mennes M. Prenatal stress and the developing brain: Risks for neurodevelopmental disorders. Dev Psychopathol. 2018;30:743\u201362. https:\/\/doi.org\/10.1017\/S0954579418000342.","journal-title":"Dev Psychopathol"},{"key":"1898_CR3","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.ejphar.2018.07.039.","volume":"834","author":"V Micale","year":"2018","unstructured":"Micale V, Drago F. Endocannabinoid system, stress and HPA axis. Eur J Pharm. 2018;834:230\u20139. https:\/\/doi.org\/10.1016\/j.ejphar.2018.07.039.","journal-title":"Eur J Pharm"},{"key":"1898_CR4","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.tins.2008.06.006.","volume":"31","author":"CM Pariante","year":"2008","unstructured":"Pariante CM, Lightman SL. The HPA axis in major depression: classical theories and new developments. Trends Neurosci. 2008;31:464\u20138. https:\/\/doi.org\/10.1016\/j.tins.2008.06.006.","journal-title":"Trends Neurosci"},{"key":"1898_CR5","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.psyneuen.2005.01.002.","volume":"30","author":"BM Gutteling","year":"2005","unstructured":"Gutteling BM, de Weerth C, Buitelaar JK. Prenatal stress and children\u2019s cortisol reaction to the first day of school. Psychoneuroendocrinology. 2005;30:541\u20139. https:\/\/doi.org\/10.1016\/j.psyneuen.2005.01.002.","journal-title":"Psychoneuroendocrinology"},{"key":"1898_CR6","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/BF03179902","volume":"56","author":"SJ Alonso","year":"2000","unstructured":"Alonso SJ, Damas C, Navarro E. Behavioral despair in mice after prenatal stress. J Physiol Biochem. 2000;56:77\u201382.","journal-title":"J Physiol Biochem"},{"key":"1898_CR7","doi-asserted-by":"publisher","first-page":"3943","DOI":"10.1523\/JNEUROSCI.16-12-03943.1996","volume":"16","author":"A Barbazanges","year":"1996","unstructured":"Barbazanges A, Piazza PV, Le Moal M, Maccari S. Maternal glucocorticoid secretion mediates long-term effects of prenatal stress. J Neurosci: Off J Soc Neurosci. 1996;16:3943\u20139.","journal-title":"J Neurosci: Off J Soc Neurosci"},{"key":"1898_CR8","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.yhbeh.2010.06.007.","volume":"59","author":"A Harris","year":"2011","unstructured":"Harris A, Seckl J. Glucocorticoids, prenatal stress and the programming of disease. Horm Behav. 2011;59:279\u201389. https:\/\/doi.org\/10.1016\/j.yhbeh.2010.06.007.","journal-title":"Horm Behav"},{"key":"1898_CR9","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3389\/neuro.08.019.2009.","volume":"3","author":"EC Cottrell","year":"2009","unstructured":"Cottrell EC, Seckl JR. Prenatal stress, glucocorticoids and the programming of adult disease. Front Behav Neurosci. 2009;3:19 https:\/\/doi.org\/10.3389\/neuro.08.019.2009.","journal-title":"Front Behav Neurosci"},{"key":"1898_CR10","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/0306-4522(87)90238-7","volume":"20","author":"D Saphier","year":"1987","unstructured":"Saphier D, Feldman S. Effects of septal and hippocampal stimuli on paraventricular nucleus neurons. Neuroscience. 1987;20:749\u201355.","journal-title":"Neuroscience"},{"key":"1898_CR11","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1196\/annals.1410.012.","volume":"1148","author":"R Jankord","year":"2008","unstructured":"Jankord R, Herman JP. Limbic regulation of hypothalamo-pituitary-adrenocortical function during acute and chronic stress. Ann N. Y Acad Sci. 2008;1148:64\u201373. https:\/\/doi.org\/10.1196\/annals.1410.012.","journal-title":"Ann N. Y Acad Sci"},{"key":"1898_CR12","doi-asserted-by":"publisher","first-page":"3072","DOI":"10.1523\/JNEUROSCI.09-09-03072.1989","volume":"9","author":"JP Herman","year":"1989","unstructured":"Herman JP, Sch\u00e4fer MK, Young EA, Thompson R, Douglass J, Akil H, et al. Evidence for hippocampal regulation of neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical axis. J Neurosci. 1989;9:3072\u201382.","journal-title":"J Neurosci"},{"key":"1898_CR13","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1210\/edrv.19.3.0331.","volume":"19","author":"ER De Kloet","year":"1998","unstructured":"De Kloet ER, Vreugdenhil E, Oitzl MS, Joels M. Brain corticosteroid receptor balance in health and disease. Endocr Rev. 1998;19:269\u2013301. https:\/\/doi.org\/10.1210\/edrv.19.3.0331.","journal-title":"Endocr Rev"},{"key":"1898_CR14","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1016\/j.neurobiolaging.2012.11.019.","volume":"34","author":"Q Wang","year":"2013","unstructured":"Wang Q, Heerikhuize JV, Aronica E, Kawata M, Seress L, Joels M, et al. Glucocorticoid receptor protein expression in human hippocampus; stability with age. Neurobiol aging. 2013;34:1662\u201373. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2012.11.019.","journal-title":"Neurobiol aging"},{"key":"1898_CR15","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1590\/S1516-44462004000300009","volume":"26","author":"MF Juruena","year":"2004","unstructured":"Juruena MF, Cleare AJ, Pariante CM. [The hypothalamic pituitary adrenal axis, glucocorticoid receptor function and relevance to depression]. Braz J Psychiatry. 2004;26:189\u2013201. \/S1516-44462004000300009.","journal-title":"Braz J Psychiatry"},{"key":"1898_CR16","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.jpsychires.2012.11.002.","volume":"47","author":"A Medina","year":"2013","unstructured":"Medina A, Seasholtz AF, Sharma V, Burke S, Bunney W, Myers RM, et al. Glucocorticoid and mineralocorticoid receptor expression in the human hippocampus in major depressive disorder. J Psychiatr Res. 2013;47:307\u201314. https:\/\/doi.org\/10.1016\/j.jpsychires.2012.11.002.","journal-title":"J Psychiatr Res"},{"key":"1898_CR17","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/S0306-4522(03)00105-2.","volume":"119","author":"K Mizoguchi","year":"2003","unstructured":"Mizoguchi K, Ishige A, Aburada M, Tabira T. Chronic stress attenuates glucocorticoid negative feedback: Involvement of the prefrontal cortex and hippocampus. Neuroscience. 2003;119:887\u201397. https:\/\/doi.org\/10.1016\/S0306-4522(03)00105-2.","journal-title":"Neuroscience"},{"key":"1898_CR18","doi-asserted-by":"publisher","first-page":"7579","DOI":"10.1523\/JNEUROSCI.0004-11.2011.","volume":"31","author":"QG Zhou","year":"2011","unstructured":"Zhou QG, Zhu LJ, Chen C, Wu HY, Luo CX, Lei C, et al. Hippocampal neuronal nitric oxide synthase mediates the stress-related depressive behaviors of glucocorticoids by downregulating glucocorticoid receptor. J Neurosci. 2011;31:7579\u201390. https:\/\/doi.org\/10.1523\/JNEUROSCI.0004-11.2011.","journal-title":"J Neurosci"},{"key":"1898_CR19","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.bbr.2017.02.014.","volume":"324","author":"S Niknazar","year":"2017","unstructured":"Niknazar S, Nahavandi A, Peyvandi AA, Peyvandi H, Roozbahany NA, Abbaszadeh HA, et al. Hippocampal NR3C1. DNA methylation can mediate part of preconception paternal stress effects in rat offspring. Behavioural Brain Res. 2017;324:71\u201376. https:\/\/doi.org\/10.1016\/j.bbr.2017.02.014.","journal-title":"Behavioural Brain Res"},{"key":"1898_CR20","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1080\/15592294.2015.1088630.","volume":"10","author":"H Palma-Gudiel","year":"2015","unstructured":"Palma-Gudiel H, Cordova-Palomera A, Eixarch E, Deuschle M, Fananas L. Maternal psychosocial stress during pregnancy alters the epigenetic signature of the glucocorticoid receptor gene promoter in their offspring: a meta-analysis. Epigenetics. 2015;10:893\u2013902. https:\/\/doi.org\/10.1080\/15592294.2015.1088630.","journal-title":"Epigenetics"},{"key":"1898_CR21","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/S0893-133x(00)00159-7.","volume":"23","author":"F Holsboer","year":"2000","unstructured":"Holsboer F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacol: Off Publ Am Coll Neuropsychopharmacol. 2000;23:477\u2013501. https:\/\/doi.org\/10.1016\/S0893-133x(00)00159-7.","journal-title":"Neuropsychopharmacol: Off Publ Am Coll Neuropsychopharmacol"},{"key":"1898_CR22","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.sbi.2014.01.008.","volume":"24","author":"EJ Miracco","year":"2014","unstructured":"Miracco EJ, Jiang J, Cash DD, Feigon J. Progress in structural studies of telomerase. Curr Opin Struct Biol. 2014;24:115\u201324. https:\/\/doi.org\/10.1016\/j.sbi.2014.01.008.","journal-title":"Curr Opin Struct Biol"},{"key":"1898_CR23","doi-asserted-by":"publisher","first-page":"160","DOI":"10.3389\/fnmol.2018.00160.","volume":"11","author":"MY Liu","year":"2018","unstructured":"Liu MY, Nemes A, Zhou QG. The emerging roles for telomerase in the central nervous system. Front Mol Neurosci. 2018;11:160 https:\/\/doi.org\/10.3389\/fnmol.2018.00160.","journal-title":"Front Mol Neurosci"},{"key":"1898_CR24","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/mp.2011.53.","volume":"17","author":"SS Drury","year":"2012","unstructured":"Drury SS, Theall K, Gleason MM, Smyke AT, Vivo ID, Wong JYY, et al. Telomere length and early severe social deprivation: linking early adversity and cellular aging. Mol Psychiatry. 2012;17:719\u201327. https:\/\/doi.org\/10.1038\/mp.2011.53.","journal-title":"Mol Psychiatry"},{"key":"1898_CR25","doi-asserted-by":"publisher","first-page":"E513","DOI":"10.1073\/pnas.1107759108.","volume":"108","author":"S Entringer","year":"2011","unstructured":"Entringer S, Epel ES, Kumsta R, Lin J, Hellhammer DH, Blackburn EH, et al. Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood. Proc Natl Acad Sci USA. 2011;108:E513\u2013518. https:\/\/doi.org\/10.1073\/pnas.1107759108.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1898_CR26","doi-asserted-by":"publisher","first-page":"94 e91","DOI":"10.1016\/j.ajog.2016.01.177.","volume":"215","author":"NM Marchetto","year":"2016","unstructured":"Marchetto NM, Glynn RA, Ferry ML, Ostojic M, Wolff SM, Yao R, et al. Prenatal stress and newborn telomere length. Am J Obstet Gynecol. 2016;215:94 e91\u201398. https:\/\/doi.org\/10.1016\/j.ajog.2016.01.177.","journal-title":"Am J Obstet Gynecol"},{"key":"1898_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.106.","volume":"6","author":"QG Zhou","year":"2016","unstructured":"Zhou QG, et al. Reactivation of Tert in the medial prefrontal cortex and hippocampus rescues aggression and depression of Tert(\u2212\/\u2212) mice. Transl Psychiatry. 2016;6:e836 https:\/\/doi.org\/10.1038\/tp.2016.106.","journal-title":"Transl Psychiatry"},{"key":"1898_CR28","doi-asserted-by":"publisher","first-page":"12258","DOI":"10.1523\/JNEUROSCI.0805-11.2011.","volume":"31","author":"QG Zhou","year":"2011","unstructured":"Zhou QG, Wu HY, Zhou H, Liu MY, Lee HW, Liu X, et al. Hippocampal telomerase is involved in the modulation of depressive behaviors. J Neurosci. 2011;31:12258\u201369. https:\/\/doi.org\/10.1523\/JNEUROSCI.0805-11.2011.","journal-title":"J Neurosci"},{"key":"1898_CR29","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.stemcr.2017.06.014.","volume":"9","author":"QG Zhou","year":"2017","unstructured":"Zhou QG, Liu MY, Lee HW, Ishikawa F, Devkota S, Shen XR, et al. Hippocampal TERT regulates spatial memory formation through modulation of neural development. Stem Cell Rep. 2017;9:543\u201356. https:\/\/doi.org\/10.1016\/j.stemcr.2017.06.014.","journal-title":"Stem Cell Rep"},{"key":"1898_CR30","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1080\/10253890.2018.1470238","volume":"21","author":"JK Gjerstad","year":"2018","unstructured":"Gjerstad JK, Lightman SL, Spiga F. Role of glucocorticoid negative feedback in the regulation of HPA axis pulsatility. Stress. 2018;21:403\u201316. https:\/\/doi.org\/10.1080\/10253890.2018.1470238","journal-title":"Stress"},{"key":"1898_CR31","doi-asserted-by":"publisher","first-page":"3754","DOI":"10.1038\/sj.onc.1211037.","volume":"27","author":"J Lee","year":"2008","unstructured":"Lee J, Sung YH, Cheong C, Choi YS, Jeon HK, Sun W, et al. TERT promotes cellular and organismal survival independently of telomerase activity. Oncogene. 2008;27:3754\u201360. https:\/\/doi.org\/10.1038\/sj.onc.1211037.","journal-title":"Oncogene"},{"key":"1898_CR32","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1038\/nature03836.","volume":"436","author":"KY Sarin","year":"2005","unstructured":"Sarin KY, Cheung P, Gilison D, Lee E, Tennen RI, Wang E, et al. Conditional telomerase induction causes proliferation of hair follicle stem cells. Nature. 2005;436:1048\u201352. https:\/\/doi.org\/10.1038\/nature03836.","journal-title":"Nature"},{"key":"1898_CR33","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1172\/JCI95731.","volume":"129","author":"QG Zhou","year":"2019","unstructured":"Zhou QG, Nemes AD, Lee D, Ro EJ, Zhang J, Nowacki AS, et al. Chemogenetic silencing of hippocampal neurons suppresses epileptic neural circuits. J Clin Invest. 2019;129:310\u201323. https:\/\/doi.org\/10.1172\/JCI95731.","journal-title":"J Clin Invest"},{"key":"1898_CR34","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1126\/science.1205295.","volume":"333","author":"RS Ray","year":"2011","unstructured":"Ray RS, Corcoran AE, Brust RD, Kim JC, Richerson GB, Nattie E, et al. Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition. Science. 2011;333:637\u201342. https:\/\/doi.org\/10.1126\/science.1205295.","journal-title":"Science"},{"key":"1898_CR35","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1210\/en.2012-1980.","volume":"154","author":"A Crudo","year":"2013","unstructured":"Crudo A, Suderman M, Moisiadis VD, Petropoulos S, Kostaki A, Hallett M, et al. Glucocorticoid programming of the fetal male hippocampal epigenome. Endocrinology. 2013;154:1168\u201380. https:\/\/doi.org\/10.1210\/en.2012-1980.","journal-title":"Endocrinology"},{"key":"1898_CR36","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1038\/nrendo.2014.74.","volume":"10","author":"VG Moisiadis","year":"2014","unstructured":"Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part 2: Mechanisms. Nat Rev Endocrinol. 2014;10:403\u201311. https:\/\/doi.org\/10.1038\/nrendo.2014.74.","journal-title":"Nat Rev Endocrinol"},{"key":"1898_CR37","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1038\/nrendo.2014.73.","volume":"10","author":"VG Moisiadis","year":"2014","unstructured":"Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part 1: Outcomes. Nat Rev Endocrinol. 2014;10:391\u2013402. https:\/\/doi.org\/10.1038\/nrendo.2014.73.","journal-title":"Nat Rev Endocrinol"},{"key":"1898_CR38","doi-asserted-by":"publisher","first-page":"152308","DOI":"10.1016\/j.tox.2019.152308.","volume":"428","author":"Y Chen","year":"2019","unstructured":"Chen Y, He Z, Chen G, Liu M, Wang H. Prenatal glucocorticoids exposure and fetal adrenal developmental programming. Toxicology. 2019;428:152308 https:\/\/doi.org\/10.1016\/j.tox.2019.152308.","journal-title":"Toxicology"},{"key":"1898_CR39","doi-asserted-by":"publisher","first-page":"964","DOI":"10.4161\/epi.28853.","volume":"9","author":"AL Non","year":"2014","unstructured":"Non AL, Binder AM, Kubzansky LD, Michels KB. Genome-wide DNA methylation in neonates exposed to maternal depression, anxiety, or SSRI medication during pregnancy. Epigenetics. 2014;9:964\u201372. https:\/\/doi.org\/10.4161\/epi.28853.","journal-title":"Epigenetics"},{"key":"1898_CR40","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.cell.2016.08.056.","volume":"167","author":"XS Liu","year":"2016","unstructured":"Liu XS, Wu H, Ji X, Stelzer Y, Wu X, Czauderna S, et al. Editing DNA methylation in the mammalian genome. Cell. 2016;167:233 https:\/\/doi.org\/10.1016\/j.cell.2016.08.056.","journal-title":"Cell"},{"key":"1898_CR41","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.cell.2015.08.046.","volume":"163","author":"Y Stelzer","year":"2015","unstructured":"Stelzer Y, Shivalila CS, Soldner F, Markoulaki S, Jaenisch R. Tracing dynamic changes of DNA methylation at single-cell resolution. Cell. 2015;163:218\u201329. https:\/\/doi.org\/10.1016\/j.cell.2015.08.046.","journal-title":"Cell"},{"key":"1898_CR42","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/j.brainresrev.2007.06.013.","volume":"57","author":"A Kapoor","year":"2008","unstructured":"Kapoor A, Petropoulos S, Matthews SG. Fetal programming of hypothalamic-pituitary-adrenal (HPA) axis function and behavior by synthetic glucocorticoids. Brain Res Rev. 2008;57:586\u201395. https:\/\/doi.org\/10.1016\/j.brainresrev.2007.06.013.","journal-title":"Brain Res Rev"},{"key":"1898_CR43","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1042\/bst0270074.","volume":"27","author":"JR Seckl","year":"1999","unstructured":"Seckl JR, Nyirenda MJ, Walker BR, Chapman KE. Glucocorticoids and fetal programming. Biochem Soc Trans. 1999;27:74\u201378. https:\/\/doi.org\/10.1042\/bst0270074.","journal-title":"Biochem Soc Trans"},{"key":"1898_CR44","doi-asserted-by":"publisher","first-page":"268","DOI":"10.3389\/fgene.2019.00268.","volume":"10","author":"JN Kuehner","year":"2019","unstructured":"Kuehner JN, Bruggeman EC, Wen Z, Yao B. Epigenetic regulations in neuropsychiatric disorders. Front Genet. 2019;10:268 https:\/\/doi.org\/10.3389\/fgene.2019.00268.","journal-title":"Front Genet"},{"key":"1898_CR45","doi-asserted-by":"publisher","first-page":"4830","DOI":"10.1073\/pnas.1524857113.","volume":"113","author":"EA Saunderson","year":"2016","unstructured":"Saunderson EA, et al. Stress-induced gene expression and behavior are controlled by DNA methylation and methyl donor availability in the dentate gyrus. Proc Natl Acad Sci USA. 2016;113:4830\u20135. https:\/\/doi.org\/10.1073\/pnas.1524857113.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1898_CR46","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1002\/dev.21604.","volume":"60","author":"DW Sosnowski","year":"2018","unstructured":"Sosnowski DW, Booth C, York TP, Amstadter AB, Kliewer W. Maternal prenatal stress and infant DNA methylation: A systematic review. Dev Psychobiol. 2018;60:127\u201339. https:\/\/doi.org\/10.1002\/dev.21604.","journal-title":"Dev Psychobiol"},{"key":"1898_CR47","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1097\/WNR.0000000000000581.","volume":"27","author":"Z Zhu","year":"2016","unstructured":"Zhu Z, Sun H, Gong X, Li H. Different effects of prenatal stress on ERK2\/CREB\/Bcl-2 expression in the hippocampus and the prefrontal cortex of adult offspring rats. Neuroreport. 2016;27:600\u20134. https:\/\/doi.org\/10.1097\/WNR.0000000000000581.","journal-title":"Neuroreport"},{"key":"1898_CR48","doi-asserted-by":"publisher","first-page":"2407","DOI":"10.1038\/npp.2017.73.","volume":"42","author":"TS Send","year":"2017","unstructured":"Send TS, Gilles M, Codd V, Wolf I, Bardtke S, Streit F, et al. Telomere length in newborns is related to maternal stress during pregnancy. Neuropsychopharmacol: Off Publ Am Coll Neuropsychopharmacol. 2017;42:2407\u201313. https:\/\/doi.org\/10.1038\/npp.2017.73.","journal-title":"Neuropsychopharmacol: Off Publ Am Coll Neuropsychopharmacol"},{"key":"1898_CR49","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2015.134.","volume":"5","author":"F Mamdani","year":"2015","unstructured":"Mamdani F, Rollins B, Morgan L, Myers RM, Barchas JD, Schatzberg AF, et al. Variable telomere length across post-mortem human brain regions and specific reduction in the hippocampus of major depressive disorder. Transl Psychiatry. 2015;5:e636 https:\/\/doi.org\/10.1038\/tp.2015.134.","journal-title":"Transl Psychiatry"},{"key":"1898_CR50","doi-asserted-by":"publisher","first-page":"244","DOI":"10.3389\/fnmol.2017.00244.","volume":"10","author":"A Pacheco","year":"2017","unstructured":"Pacheco A, Aguayo FI, Aliaga E, Mu\u00f1oz M, Garc\u00eda-Rojo G, Olave FA, et al. Chronic stress triggers expression of immediate early genes and differentially affects the expression of AMPA and NMDA subunits in dorsal and ventral hippocampus of rats. Front Mol Neurosci. 2017;10:244 https:\/\/doi.org\/10.3389\/fnmol.2017.00244.","journal-title":"Front Mol Neurosci"},{"key":"1898_CR51","doi-asserted-by":"publisher","first-page":"7770","DOI":"10.1523\/JNEUROSCI.5352-12.2013.","volume":"33","author":"TJ Schoenfeld","year":"2013","unstructured":"Schoenfeld TJ, Rada P, Pieruzzini PR, Hsueh B, Gould E. Physical exercise prevents stress-induced activation of granule neurons and enhances local inhibitory mechanisms in the dentate gyrus. J Neurosci: Off J Soc Neurosci. 2013;33:7770\u20137. https:\/\/doi.org\/10.1523\/JNEUROSCI.5352-12.2013.","journal-title":"J Neurosci: Off J Soc Neurosci"},{"key":"1898_CR52","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1007\/s00213-010-1835-6.","volume":"210","author":"N Elizalde","year":"2010","unstructured":"Elizalde N, Garc\u00eda-Garc\u00eda AL, Totterdell S, Gendive N, Venzala E, Ramirez MJ, et al. Sustained stress-induced changes in mice as a model for chronic depression. Psychopharmacology. 2010;210:393\u2013406. https:\/\/doi.org\/10.1007\/s00213-010-1835-6.","journal-title":"Psychopharmacology"},{"key":"1898_CR53","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/s0006-3223(03)00698-x.","volume":"54","author":"CL Coe","year":"2003","unstructured":"Coe CL, Kramer M, Cz\u00e9h B, Gould E, Reeves AJ, Kirschbaum C, et al. Prenatal stress diminishes neurogenesis in the dentate gyrus of juvenile rhesus monkeys. Biol Psychiatry. 2003;54:1025\u201334. https:\/\/doi.org\/10.1016\/s0006-3223(03)00698-x.","journal-title":"Biol Psychiatry"},{"key":"1898_CR54","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1002\/syn.21512.","volume":"66","author":"R Mychasiuk","year":"2012","unstructured":"Mychasiuk R, Gibb R, Kolb B. Prenatal stress alters dendritic morphology and synaptic connectivity in the prefrontal cortex and hippocampus of developing offspring. Synapse. 2012;66:308\u201314. https:\/\/doi.org\/10.1002\/syn.21512.","journal-title":"Synapse"},{"key":"1898_CR55","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1016\/j.neubiorev.2011.02.003.","volume":"35","author":"JM Koolhaas","year":"2011","unstructured":"Koolhaas JM, Bartolomucci A, Buwalda B, de Boer SF, Fl\u00fcgge G, Korte SM, et al. Stress revisited: A critical evaluation of the stress concept. Neurosci Biobehav R. 2011;35:1291\u2013301. https:\/\/doi.org\/10.1016\/j.neubiorev.2011.02.003.","journal-title":"Neurosci Biobehav R"},{"key":"1898_CR56","first-page":"69","volume":"640","author":"JM Koolhaas","year":"1997","unstructured":"Koolhaas JM, De Boer SF, De Rutter AJ, Meerlo P, Sgoifo A. Social stress in rats and mice. Acta Physiol Scand Suppl. 1997;640:69\u201372.","journal-title":"Acta Physiol Scand Suppl"},{"key":"1898_CR57","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.yhbeh.2005.08.005","volume":"49","author":"H Bonilla-Jaime","year":"2006","unstructured":"Bonilla-Jaime H, V\u00e1zquez-Palacios G, Arteaga-Silva M, Retana-M\u00e1rquez S. Hormonal responses to different sexually related conditions in male rats. Horm Behav. 2006;49:376\u201382.","journal-title":"Horm Behav"},{"key":"1898_CR58","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.yhbeh.2006.06.010.","volume":"50","author":"AR Tarullo","year":"2006","unstructured":"Tarullo AR, Gunnar MR. Child maltreatment and the developing HPA axis. Hormones Behav. 2006;50:632\u20139. https:\/\/doi.org\/10.1016\/j.yhbeh.2006.06.010.","journal-title":"Hormones Behav"},{"key":"1898_CR59","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.1002\/bmc.3232.","volume":"28","author":"H Li","year":"2014","unstructured":"Li H, Liu X, Poh YP, Wu L, Zhou QG, Cai BC. Rapid determination of corticosterone in mouse plasma by ultra fast liquid chromatography-tandem mass spectrometry. Biomed Chromatogr. 2014;28:1860\u20133. https:\/\/doi.org\/10.1002\/bmc.3232.","journal-title":"Biomed Chromatogr"}],"container-title":["Molecular Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41380-022-01898-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-022-01898-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-022-01898-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T10:20:45Z","timestamp":1680862845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41380-022-01898-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,8]]},"references-count":59,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["1898"],"URL":"https:\/\/doi.org\/10.1038\/s41380-022-01898-9","relation":{},"ISSN":["1359-4184","1476-5578"],"issn-type":[{"value":"1359-4184","type":"print"},{"value":"1476-5578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,8]]},"assertion":[{"value":"24 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 December 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}