{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:11:12Z","timestamp":1790759472085,"version":"4.1.0"},"reference-count":93,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T00:00:00Z","timestamp":1676246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research (CIHR) Project Scheme","doi-asserted-by":"publisher","award":["363195"],"award-info":[{"award-number":["363195"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prenatal maternal stress is linked to adverse pregnancy and infant outcomes, including shortened gestation lengths, low birth weights, cardio-metabolic dysfunction, and cognitive and behavioural problems. Stress disrupts the homeostatic milieu of pregnancy by altering inflammatory and neuroendocrine mediators. These stress-induced phenotypic changes can be passed on to the offspring epigenetically. We investigated the effects of gestational chronic variable stress (CVS) in rats using restraint and social isolation stress in the parental F0 generation and its transgenerational transmission across three generations of female offspring (F1\u2013F3). A subset of F1 rats was housed in an enriched environment (EE) to mitigate the adverse effects of CVS. We found that CVS is transmitted across generations and induces inflammatory changes in the uterus. CVS did not alter any gestational lengths or birth weights. However, inflammatory and endocrine markers changed in the uterine tissues of stressed mothers and their offspring, suggesting that stress is transgenerationally transmitted. The F2 offspring reared in EE had increased birth weights, but their uterine gene expression patterns remained comparable to those of stressed animals. Thus, ancestral CVS induced changes transgenerationally in fetal programming of uterine stress markers over three generations of offspring, and EE housing did not mitigate these effects.<\/jats:p>","DOI":"10.3390\/ijms24043734","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T05:25:26Z","timestamp":1676265926000},"page":"3734","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Environmental Enrichment Promotes Transgenerational Programming of Uterine Inflammatory and Stress Markers Comparable to Gestational Chronic Variable Stress"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3141-7883","authenticated-orcid":false,"given":"Nayara A.","family":"Lopes","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2R3, Canada"},{"name":"Department of Physiology, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirela","family":"Ambeskovic","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0970-6355","authenticated-orcid":false,"given":"Stephanie E.","family":"King","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamshid","family":"Faraji","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasrin","family":"Soltanpour","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin A.","family":"Falkenberg","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Scheidl","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansi","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5801-7716","authenticated-orcid":false,"given":"Gerlinde A. S.","family":"Metz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2R3, Canada"},{"name":"Department of Neuroscience, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Olson","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2R3, Canada"},{"name":"Department of Physiology, University of Alberta, Edmonton, AB T6G 2R3, Canada"},{"name":"Department of Neuroscience, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada"},{"name":"Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1097\/01.grf.0000142512.38733.8c","article-title":"Stress and preterm birth","volume":"47","author":"Hobel","year":"2004","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1177\/0884217503257484","article-title":"Psychological and physiological stress: Impact on preterm birth","volume":"32","author":"Gennaro","year":"2003","journal-title":"J. Obstet. Gynecol. Neonatal. Nurs."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Yao, Y., Robinson, A.M., Zucchi, F.C., Robbins, J.C., Babenko, O., Kovalchuk, O., Kovalchuk, I., Olson, D.M., and Metz, G.A. (2014). Ancestral exposure to stress epigenetically programs preterm birth risk and adverse maternal and newborn outcomes. BMC Med., 12.","DOI":"10.1186\/s12916-014-0121-6"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"254","DOI":"10.3389\/fimmu.2020.00254","article-title":"Prenatal Maternal Stress Causes Preterm Birth and Affects Neonatal Adaptive Immunity in Mice","volume":"11","author":"Romero","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/s41398-020-00876-5","article-title":"Prenatal stress causes intrauterine inflammation and serotonergic dysfunction, and long-term behavioral deficits through microbe- and CCL2-dependent mechanisms","volume":"10","author":"Chen","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100229","DOI":"10.1016\/j.ajogmf.2020.100229","article-title":"Effects of psychological stress on adverse pregnancy outcomes and nonpharmacologic approaches for reduction: An expert review","volume":"2","author":"Traylor","year":"2020","journal-title":"Am. J. Obstet. Gynecol. MFM"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.reprotox.2007.09.001","article-title":"What is an epigenetic transgenerational phenotype? F3 or F2","volume":"25","author":"Skinner","year":"2008","journal-title":"Reprod. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"506","DOI":"10.5468\/ogs.2017.60.6.506","article-title":"What is fetal programming?: A lifetime health is under the control of in utero health","volume":"60","author":"Kwon","year":"2017","journal-title":"Obstet. Gynecol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1042\/CS19980019","article-title":"In utero programming of chronic disease","volume":"95","author":"Barker","year":"1998","journal-title":"Clin. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/0140-6736(93)91224-A","article-title":"Fetal nutrition and cardiovascular disease in adult life","volume":"341","author":"Barker","year":"1993","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.tem.2009.12.007","article-title":"Epigenetic transgenerational actions of environmental factors in disease etiology","volume":"21","author":"Skinner","year":"2010","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"dvy016","DOI":"10.1093\/eep\/dvy016","article-title":"Environmentally induced epigenetic transgenerational inheritance of disease","volume":"4","author":"Nilsson","year":"2018","journal-title":"Environ. Epigenet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3109\/10253890.2013.876404","article-title":"Prenatal maternal stress exposure and immune function in the offspring","volume":"17","author":"Veru","year":"2014","journal-title":"Stress"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.neubiorev.2021.04.032","article-title":"Long-lasting effects of prenatal stress on HPA axis and inflammation: A systematic review and multilevel meta-analysis in rodent studies","volume":"127","author":"Creutzberg","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/ppe.12042","article-title":"Maternal stress\/distress, hormonal pathways and spontaneous preterm birth","volume":"27","author":"Kramer","year":"2013","journal-title":"Paediatr. Perinat. Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1210\/en.2017-00896","article-title":"Prenatal Stress, Glucocorticoids, and Developmental Programming of the Stress Response","volume":"159","author":"McGowan","year":"2018","journal-title":"Endocrinology"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lopes, N.A., Falkenberg, E.A., Wiley, C., Patel, V., Serrano-Lomelin, J., Fang, X., Weiler, A.M., McCreary, J.K., Metz, G.A.S., and Olson, D.M. (2022). Social Isolation Stress Modulates Pregnancy Outcomes and the Inflammatory Profile of Rat Uterus. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116169"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1080\/17446651.2017.1356222","article-title":"Developmental origins of the human hypothalamic-pituitary-adrenal axis","volume":"12","author":"Howland","year":"2017","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1113\/jphysiol.2006.105254","article-title":"Fetal programming of hypothalamo-pituitary-adrenal function: Prenatal stress and glucocorticoids","volume":"572","author":"Kapoor","year":"2006","journal-title":"J. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"104.e1","DOI":"10.1016\/j.ajog.2008.08.032","article-title":"Term labor is associated with a core inflammatory response in human fetal membranes, myometrium, and cervix","volume":"200","author":"Bollapragada","year":"2009","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"660983","DOI":"10.3389\/fcimb.2021.660983","article-title":"Inflammatory Amplification: A Central Tenet of Uterine Transition for Labor","volume":"11","author":"Leimert","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.bbi.2006.08.006","article-title":"Psychosocial stress increases inflammatory markers and alters cytokine production across pregnancy","volume":"21","author":"Okun","year":"2007","journal-title":"Brain Behav. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1097\/PSY.0b013e31829bbc89","article-title":"Stress-induced inflammatory responses in women: Effects of race and pregnancy","volume":"75","author":"Christian","year":"2013","journal-title":"Psychosom. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1097\/01.psy.0000170331.74960.ad","article-title":"Prenatal stress alters cytokine levels in a manner that may endanger human pregnancy","volume":"67","author":"Okun","year":"2005","journal-title":"Psychosom. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.bbi.2012.02.009","article-title":"The occurrence of preterm delivery is linked to pregnancy-specific distress and elevated inflammatory markers across gestation","volume":"26","author":"Lobel","year":"2012","journal-title":"Brain Behav. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/aje\/kwf176","article-title":"Maternal stress and preterm birth","volume":"157","author":"Dole","year":"2003","journal-title":"Am. J. Epidemiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.bbi.2018.11.009","article-title":"Elevated pro-inflammatory gene expression in the third trimester of pregnancy in mothers who experienced stressful life events","volume":"76","author":"Ross","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/biolre\/ioy166","article-title":"Prenatal two-hit stress affects maternal and offspring pregnancy outcomes and uterine gene expression in rats: Match or mismatch?","volume":"100","author":"Verstraeten","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"134368","DOI":"10.1016\/j.neulet.2019.134368","article-title":"Cellular stress mechanisms of prenatal maternal stress: Heat shock factors and oxidative stress","volume":"709","author":"Dowell","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5116","DOI":"10.1093\/cercor\/bhz052","article-title":"The Role of Redox Dysregulation in the Effects of Prenatal Stress on Embryonic Interneuron Migration","volume":"29","author":"Bittle","year":"2019","journal-title":"Cereb. Cortex"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12974-018-1079-7","article-title":"The role of glucocorticoid, interleukin-1\u03b2, and antioxidants in prenatal stress effects on embryonic microglia","volume":"15","author":"Bittle","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Karanikas, E., Daskalakis, N.P., and Agorastos, A. (2021). Oxidative Dysregulation in Early Life Stress and Posttraumatic Stress Disorder: A Comprehensive Review. Brain Sci., 11.","DOI":"10.3390\/brainsci11060723"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1177\/1099800418791028","article-title":"Oxidative Stress and Preterm Birth: An Integrative Review","volume":"20","author":"Moore","year":"2018","journal-title":"Biol. Res. Nurs."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.jsgi.2005.01.029","article-title":"The effects of chorioamnionitis and betamethasone on 11beta hydroxysteroid dehydrogenase types 1 and 2 and the glucocorticoid receptor in preterm human placenta","volume":"12","author":"Johnstone","year":"2005","journal-title":"J. Soc. Gynecol. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"E282","DOI":"10.1152\/ajpendo.00328.2005","article-title":"Pro-inflammatory cytokines inhibit human placental 11beta-hydroxysteroid dehydrogenase type 2 activity through Ca2+ and cAMP pathways","volume":"290","author":"Kossintseva","year":"2006","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.reprotox.2022.03.016","article-title":"Effects of prenatal hypoxia on placental glucocorticoid barrier: Mechanistic insight from experiments in rats","volume":"110","author":"Ji","year":"2022","journal-title":"Reprod. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4797","DOI":"10.1210\/jc.2002-020310","article-title":"Oxygen Regulation of Placental 11\u03b2-Hydroxysteroid Dehydrogenase 2: Physiological and Pathological Implications","volume":"87","author":"Alfaidy","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.biopsych.2018.08.018","article-title":"Inflammation: A Proposed Intermediary between Maternal Stress and Offspring Neuropsychiatric Risk","volume":"85","author":"Hantsoo","year":"2019","journal-title":"Biol. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"103273","DOI":"10.1016\/j.jri.2021.103273","article-title":"Maternal environmental enrichment modulates the immune response against an inflammatory challenge during gestation and protects the offspring","volume":"144","author":"Schander","year":"2021","journal-title":"J. Reprod. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"37814","DOI":"10.1038\/srep37814","article-title":"Environmental Intervention as a Therapy for Adverse Programming by Ancestral Stress","volume":"6","author":"McCreary","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_41","first-page":"139","article-title":"Animal Models of Brain Plasticity and Behavioral Change","volume":"Volume 9","author":"Kolb","year":"2003","journal-title":"Handbook of Neuropsychology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1530\/REP-19-0572","article-title":"The enrichment of maternal environment prevents preterm birth in a mice model","volume":"159","author":"Schander","year":"2020","journal-title":"Reproduction"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"dvw013","DOI":"10.1093\/eep\/dvw013","article-title":"Environmental enrichment as an intervention for adverse health outcomes of prenatal stress","volume":"2","author":"McCreary","year":"2016","journal-title":"Environ. Epigenet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.neulet.2016.08.059","article-title":"Environmental enrichment mitigates the impact of ancestral stress on motor skill and corticospinal tract plasticity","volume":"632","author":"McCreary","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5807","DOI":"10.1113\/JP275472","article-title":"Increased susceptibility to cardiovascular disease in offspring born from dams of advanced maternal age","volume":"596","author":"Cooke","year":"2018","journal-title":"J. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1002\/dev.20316","article-title":"Influence of prenatal psychosocial stress on cytokine production in adult women","volume":"50","author":"Entringer","year":"2008","journal-title":"Dev. Psychobiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5614","DOI":"10.4049\/jimmunol.161.10.5614","article-title":"IL-1 receptor accessory protein is an essential component of the IL-1 receptor","volume":"161","author":"Cullinan","year":"1998","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"R101","DOI":"10.1530\/JOE-16-0157","article-title":"Myometrial cytokines and their role in the onset of labour","volume":"231","author":"Sivarajasingam","year":"2016","journal-title":"J. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lilliecreutz, C., Lar\u00e9n, J., Sydsj\u00f6, G., and Josefsson, A. (2016). Effect of maternal stress during pregnancy on the risk for preterm birth. BMC Pregnancy Childbirth, 16.","DOI":"10.1186\/s12884-015-0775-x"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.clp.2011.06.007","article-title":"The contribution of maternal stress to preterm birth: Issues and considerations","volume":"38","author":"Wadhwa","year":"2011","journal-title":"Clin. Perinatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"438.e1","DOI":"10.1016\/j.ajog.2013.07.003","article-title":"The combined association of psychosocial stress and chronic hypertension with preeclampsia","volume":"209","author":"Yu","year":"2013","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.mehy.2011.04.007","article-title":"Distress conditions during pregnancy may lead to pre-eclampsia by increasing cortisol levels and altering lymphocyte sensitivity to glucocorticoids","volume":"77","author":"Vianna","year":"2011","journal-title":"Med. Hypotheses"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.bbi.2016.12.021","article-title":"Prenatal stress affects placental cytokines and neurotrophins, commensal microbes, and anxiety-like behavior in adult female offspring","volume":"64","author":"Gur","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1210\/en.2014-1040","article-title":"Prenatal stress-induced increases in placental inflammation and offspring hyperactivity are male-specific and ameliorated by maternal antiinflammatory treatment","volume":"155","author":"Bronson","year":"2014","journal-title":"Endocrinology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"112332","DOI":"10.1016\/j.bbr.2019.112332","article-title":"Environmental determinants of behavioural responses to short-term stress in rats: Evidence for inhibitory effect of ambient landmarks","volume":"379","author":"Faraji","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5277","DOI":"10.1038\/s41598-017-05440-8","article-title":"Lack of Social Support Raises Stress Vulnerability in Rats with a History of Ancestral Stress","volume":"7","author":"Faraji","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bbr.2012.02.040","article-title":"Prenatal exposure to chronic mild stress increases corticosterone levels in the amniotic fluid and induces cognitive deficits in female offspring, improved by treatment with the antidepressant drug amitriptyline","volume":"231","author":"Aziz","year":"2012","journal-title":"Behav. Brain Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Jafari, Z., Mehla, J., Afrashteh, N., Kolb, B.E., and Mohajerani, M.H. (2017). Corticosterone response to gestational stress and postpartum memory function in mice. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180306"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1113\/jphysiol.2014.271460","article-title":"The biology of developmental plasticity and the Predictive Adaptive Response hypothesis","volume":"592","author":"Bateson","year":"2014","journal-title":"J. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1016\/j.psyneuen.2013.06.008","article-title":"The three-hit concept of vulnerability and resilience: Toward understanding adaptation to early-life adversity outcome","volume":"38","author":"Daskalakis","year":"2013","journal-title":"Psychoneuroendocrinology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.bbi.2019.05.004","article-title":"Resilience to chronic stress is associated with specific neurobiological, neuroendocrine and immune responses","volume":"80","author":"Gururajan","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.euroneuro.2012.09.011","article-title":"Vulnerability versus resilience to prenatal stress in male and female rats; implications from gene expression profiles in the hippocampus and frontal cortex","volume":"23","author":"Kenis","year":"2013","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ynstr.2014.10.006","article-title":"Individual differences in the effects of prenatal stress exposure in rodents","volume":"1","author":"Boersma","year":"2015","journal-title":"Neurobiol. Stress"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.biopsych.2010.05.036","article-title":"Epigenetic transmission of the impact of early stress across generations","volume":"68","author":"Franklin","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e12866","DOI":"10.14814\/phy2.12866","article-title":"Interleukin (IL)-1 in rat parturition: IL-1 receptors 1 and 2 and accessory proteins abundance in pregnant rat uterus at term\u2014Regulation by progesterone","volume":"4","author":"Ishiguro","year":"2016","journal-title":"Physiol. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1111\/jcmm.13985","article-title":"Potential regulatory network in the PSG10P\/miR-19a-3p\/IL1RAP pathway is possibly involved in preeclampsia pathogenesis","volume":"23","author":"Wang","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1210\/er.2013-1012","article-title":"Early-life glucocorticoid exposure: The hypothalamic-pituitary-adrenal axis, placental function, and long-term disease risk","volume":"34","author":"Braun","year":"2013","journal-title":"Endocr. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.placenta.2014.03.005","article-title":"Roles of glucocorticoids in human parturition: A controversial fact?","volume":"35","author":"Li","year":"2014","journal-title":"Placenta"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1177\/1753495X19847832","article-title":"Glucocorticoids in pregnancy","volume":"13","author":"Pofi","year":"2020","journal-title":"Obstet. Med."},{"key":"ref_70","first-page":"652738","article-title":"Modulation of Immunity and Inflammation by the Mineralocorticoid Receptor and Aldosterone","volume":"2015","author":"Vecchiola","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1007\/s11010-022-04499-w","article-title":"Placental oxidative stress and monoamine oxidase expression are increased in severe preeclampsia: A pilot study","volume":"477","author":"Sturza","year":"2022","journal-title":"Mol. Cell. Biochem."},{"key":"ref_72","first-page":"287","article-title":"First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid","volume":"54","author":"Ighodaro","year":"2018","journal-title":"Alex. J. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s12958-018-0391-5","article-title":"A novel and compact review on the role of oxidative stress in female reproduction","volume":"16","author":"Lu","year":"2018","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1267\/ahc.11054","article-title":"Environmental Enrichment during Gestation Improves Behavior Consequences and Synaptic Plasticity in Hippocampus of Prenatal-Stressed Offspring Rats","volume":"45","author":"Li","year":"2012","journal-title":"Acta Histochem. Cytochem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1096\/fj.02-1032fje","article-title":"The postnatal environment can counteract prenatal effects on cognitive ability, cell proliferation, and synaptic protein expression","volume":"17","author":"Koo","year":"2003","journal-title":"FASEB J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0304-3940(92)90494-R","article-title":"Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment","volume":"138","author":"Falkenberg","year":"1992","journal-title":"Neurosci. Lett."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nlm.2007.03.009","article-title":"The behavioral effects of enriched housing are not altered by serotonin depletion but enrichment alters hippocampal neurochemistry","volume":"88","author":"Galani","year":"2007","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.neuroscience.2016.05.046","article-title":"Altered brain morphology and functional connectivity reflect a vulnerable affective state after cumulative multigenerational stress in rats","volume":"330","author":"McCreary","year":"2016","journal-title":"Neuroscience"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/dev.20592","article-title":"Transgenerational effects of infantile adversity and enrichment in male and female rats","volume":"54","author":"Leshem","year":"2012","journal-title":"Dev. Psychobiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1242\/bio.015024","article-title":"The effects of laboratory housing and spatial enrichment on brain size and metabolic rate in the eastern mosquitofish, Gambusia holbrooki","volume":"5","author":"Turschwell","year":"2016","journal-title":"Biol. Open"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1002\/ece3.2717","article-title":"Environmental enrichment, sexual dimorphism, and brain size in sticklebacks","volume":"7","author":"Toli","year":"2017","journal-title":"Ecol. Evol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Fairhurst, G.D., Frey, M.D., Reichert, J.F., Szelest, I., Kelly, D.M., and Bortolotti, G.R. (2011). Does environmental enrichment reduce stress? An integrated measure of corticosterone from feathers provides a novel perspective. PLoS ONE, 6.","DOI":"10.1371\/annotation\/3ac615cc-2ecf-4d3e-9281-3b9b9b04cf08"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1365-2826.2004.01173.x","article-title":"Effect of environmental enrichment on stress related systems in rats","volume":"16","author":"Moncek","year":"2004","journal-title":"J. Neuroendocrinol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ynstr.2016.09.002","article-title":"Forced treadmill exercise can induce stress and increase neuronal damage in a mouse model of global cerebral ischemia","volume":"5","author":"Svensson","year":"2016","journal-title":"Neurobiol. Stress"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s12970-016-0155-6","article-title":"Exercise-induced stress behavior, gut-microbiota-brain axis and diet: A systematic review for athletes","volume":"13","author":"Clark","year":"2016","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/6368","article-title":"Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus","volume":"2","author":"Kempermann","year":"1999","journal-title":"Nat. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"186","DOI":"10.4103\/cjp.cjp_39_21","article-title":"Exercise-induced increases of corticosterone contribute to exercise-enhanced adult hippocampal neurogenesis in mice","volume":"64","author":"Tsai","year":"2021","journal-title":"Chin. J. Physiol."},{"key":"ref_88","first-page":"jeb202234","article-title":"The effect of environmental enrichment on behavioral variability depends on genotype, behavior, and type of enrichment","volume":"222","author":"Ho","year":"2019","journal-title":"J. Exp. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e35690","DOI":"10.7554\/eLife.35690","article-title":"Selective increases in inter-individual variability in response to environmental enrichment in female mice","volume":"7","author":"Zocher","year":"2018","journal-title":"Elife"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"292","DOI":"10.3389\/fnmol.2018.00292","article-title":"Epigenetic Inheritance: Concepts, Mechanisms and Perspectives","volume":"11","author":"Lacal","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Burggren, W. (2016). Epigenetic Inheritance and Its Role in Evolutionary Biology: Re-Evaluation and New Perspectives. Biology, 5.","DOI":"10.3390\/biology5020024"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1093\/biolre\/ioy232","article-title":"Maternal and fetal intrauterine tissue crosstalk promotes pro-inflammatory amplification and uterine transition \u2020","volume":"100","author":"Leimert","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3734\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:33:24Z","timestamp":1760121204000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,13]]},"references-count":93,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24043734"],"URL":"https:\/\/doi.org\/10.3390\/ijms24043734","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,13]]}}}