{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:28:49Z","timestamp":1790803729663,"version":"4.1.0"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,6,28]],"date-time":"2016-06-28T00:00:00Z","timestamp":1467072000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,6,28]],"date-time":"2016-06-28T00:00:00Z","timestamp":1467072000000},"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":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Psychological stress during pregnancy increases the risk of childhood wheeze and asthma. However, the transmitting mechanisms remain largely unknown. Since epigenetic alterations have emerged as a link between perturbations in the prenatal environment and an increased disease risk we used whole genome bisulfite sequencing (WGBS) to analyze changes in DNA methylation in mothers and their children related to prenatal psychosocial stress and assessed its role in the development of wheeze in the child. We evaluated genomic regions altered in their methylation level due to maternal stress based of WGBS data of 10 mother-child-pairs. These data were complemented by longitudinal targeted methylation and transcriptional analyses in children from our prospective mother-child cohort LINA for whom maternal stress and wheezing information was available (n\u2009=\u2009443). High maternal stress was associated with an increased risk for persistent wheezing in the child until the age of 5. Both mothers and children showed genome-wide alterations in DNA-methylation specifically in enhancer elements. Deregulated neuroendocrine and neurotransmitter receptor interactions were observed in stressed mothers and their children. In children but not in mothers, calcium- and Wnt-signaling required for lung maturation in the prenatal period were epigenetically deregulated and could be linked with wheezing later in children\u2019s life.<\/jats:p>","DOI":"10.1038\/srep28616","type":"journal-article","created":{"date-parts":[[2016,6,28]],"date-time":"2016-06-28T09:27:09Z","timestamp":1467106029000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Prenatal maternal stress and wheeze in children: novel insights into epigenetic regulation"],"prefix":"10.1038","volume":"6","author":[{"given":"Saskia","family":"Trump","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Bieg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuguang","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loreen","family":"Th\u00fcrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveed","family":"Ishaque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"R\u00f6der","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunda","family":"Herberth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lawerenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Borte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schlesner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Plass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolle","family":"Diessl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Eszlinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"M\u00fccke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst-Dietrich","family":"Elvers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk K.","family":"Wissenbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"von Bergen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Weichenhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalind J.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Lehmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Eils","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,28]]},"reference":[{"key":"BFsrep28616_CR1","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1164\/rccm.201201-0162OC","volume":"186","author":"YH Mathilda Chiu","year":"2012","unstructured":"Mathilda Chiu, Y. H., Coull, B. A., Cohen, S., Wooley, A. & Wright, R. J. Prenatal and postnatal maternal stress and wheeze in urban children: effect of maternal sensitization. American Journal of Respiratory and Critical Care Medicine 186, 147\u2013154, doi: 10.1164\/rccm.201201-0162OC (2012).","journal-title":"American Journal of Respiratory and Critical Care Medicine"},{"key":"BFsrep28616_CR2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/j.1365-3016.2007.00879.x","volume":"21","author":"RJ Wright","year":"2007","unstructured":"Wright, R. J. Prenatal maternal stress and early caregiving experiences: implications for childhood asthma risk. Paediatric and Perinatal Epidemiology 21 Suppl 3, 8\u201314, doi: 10.1111\/j.1365-3016.2007.00879.x (2007).","journal-title":"Paediatric and Perinatal Epidemiology"},{"key":"BFsrep28616_CR3","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1111\/j.1399-3038.2012.01346.x","volume":"23","author":"R de Marco","year":"2012","unstructured":"de Marco, R. et al. Foetal exposure to maternal stressful events increases the risk of having asthma and atopic diseases in childhood. Pediatric Allergy and Immunology: Official Publication of the European Society of Pediatric Allergy and Immunology 23, 724\u2013729, doi: 10.1111\/j.1399-3038.2012.01346.x (2012).","journal-title":"Pediatric Allergy and Immunology: Official Publication of the European Society of Pediatric Allergy and Immunology"},{"key":"BFsrep28616_CR4","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1097\/PSY.0b013e31825ac5e7","volume":"74","author":"AS Khashan","year":"2012","unstructured":"Khashan, A. S. et al. Prenatal stress and risk of asthma hospitalization in the offspring: a Swedish population-based study. Psychosomatic Medicine 74, 635\u2013641, doi: 10.1097\/PSY.0b013e31825ac5e7 (2012).","journal-title":"Psychosomatic Medicine"},{"key":"BFsrep28616_CR5","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1111\/j.1398-9995.2012.02791.x","volume":"67","author":"JL Peters","year":"2012","unstructured":"Peters, J. L. et al. Prenatal negative life events increases cord blood IgE: interactions with dust mite allergen and maternal atopy. Allergy 67, 545\u2013551, doi: 10.1111\/j.1398-9995.2012.02791.x (2012).","journal-title":"Allergy"},{"key":"BFsrep28616_CR6","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.bbi.2007.05.007","volume":"22","author":"E Merlot","year":"2008","unstructured":"Merlot, E., Couret, D. & Otten, W. Prenatal stress, fetal imprinting and immunity. Brain, Behavior, and Immunity 22, 42\u201351, doi: 10.1016\/j.bbi.2007.05.007 (2008).","journal-title":"Brain, Behavior, and Immunity"},{"key":"BFsrep28616_CR7","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.vetimm.2009.03.003","volume":"131","author":"D Couret","year":"2009","unstructured":"Couret, D., Jamin, A., Kuntz-Simon, G., Prunier, A. & Merlot, E. Maternal stress during late gestation has moderate but long-lasting effects on the immune system of the piglets. Veterinary Immunology and Immunopathology 131, 17\u201324, doi: 10.1016\/j.vetimm.2009.03.003 (2009).","journal-title":"Veterinary Immunology and Immunopathology"},{"key":"BFsrep28616_CR8","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.resp.2005.04.014","volume":"149","author":"R Kinkead","year":"2005","unstructured":"Kinkead, R. et al. Neonatal maternal separation and early life programming of the hypoxic ventilatory response in rats. Respiratory Physiology & Neurobiology 149, 313\u2013324, doi: 10.1016\/j.resp.2005.04.014 (2005).","journal-title":"Respiratory Physiology & Neurobiology"},{"key":"BFsrep28616_CR9","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1152\/jappl.2001.90.5.1729","volume":"90","author":"R Kinkead","year":"2001","unstructured":"Kinkead, R., Dupenloup, L., Valois, N. & Gulemetova, R. Stress-induced attenuation of the hypercapnic ventilatory response in awake rats. Journal of Applied Physiology 90, 1729\u20131735 (2001).","journal-title":"Journal of Applied Physiology"},{"key":"BFsrep28616_CR10","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1111\/j.1365-2222.2004.1928.x","volume":"34","author":"YC Lin","year":"2004","unstructured":"Lin, Y. C., Wen, H. J., Lee, Y. L. & Guo, Y. L. Are maternal psychosocial factors associated with cord immunoglobulin E in addition to family atopic history and mother immunoglobulin E? Clinical and Experimental Allergy: Journal of the BRITISH Society for Allergy and Clinical Immunology 34, 548\u2013554, doi: 10.1111\/j.1365-2222.2004.1928.x (2004).","journal-title":"Clinical and Experimental Allergy: Journal of the BRITISH Society for Allergy and Clinical Immunology"},{"key":"BFsrep28616_CR11","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jaci.2005.04.017","volume":"116","author":"PG Holt","year":"2005","unstructured":"Holt, P. G., Upham, J. W. & Sly, P. D. Contemporaneous maturation of immunologic and respiratory functions during early childhood: implications for development of asthma prevention strategies. The Journal of Allergy and Clinical Immunology 116, 16\u201324; quiz 25, doi: 10.1016\/j.jaci.2005.04.017 (2005).","journal-title":"The Journal of Allergy and Clinical Immunology"},{"key":"BFsrep28616_CR12","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.prrv.2006.03.001","volume":"7","author":"SL Prescott","year":"2006","unstructured":"Prescott, S. L. The development of respiratory inflammation in children. Paediatric Respiratory Reviews 7, 89\u201396, doi: 10.1016\/j.prrv.2006.03.001 (2006).","journal-title":"Paediatric Respiratory Reviews"},{"key":"BFsrep28616_CR13","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1016\/j.jaci.2014.07.005","volume":"134","author":"SL Rosenberg","year":"2014","unstructured":"Rosenberg, S. L., Miller, G. E., Brehm, J. M. & Celedon, J. C. Stress and asthma: Novel insights on genetic, epigenetic, and immunologic mechanisms. The Journal of Allergy and Clinical Immunology 134, 1009\u20131015, doi: 10.1016\/j.jaci.2014.07.005 (2014).","journal-title":"The Journal of Allergy and Clinical Immunology"},{"key":"BFsrep28616_CR14","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1111\/j.1398-9995.2011.02767.x","volume":"67","author":"D Hinz","year":"2012","unstructured":"Hinz, D. et al. Cord blood Tregs with stable FOXP3 expression are influenced by prenatal environment and associated with atopic dermatitis at the age of one year. Allergy 67, 380\u2013389, doi: 10.1111\/j.1398-9995.2011.02767.x (2012).","journal-title":"Allergy"},{"key":"BFsrep28616_CR15","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1056\/NEJM199501193320301","volume":"332","author":"FD Martinez","year":"1995","unstructured":"Martinez, F. D., W., A. L., T., L. M., Holberg, C. J., Halonen, M. & Morgan, W. J. Asthma and wheezing in the first six years of life. The Group Health Mediacl Associates. The New England Journal of Medicine 332, 133\u2013138 (1995).","journal-title":"The New England Journal of Medicine"},{"key":"BFsrep28616_CR16","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1111\/j.1398-9995.2011.02587.x","volume":"66","author":"G Herberth","year":"2011","unstructured":"Herberth, G. et al. Maternal immune status in pregnancy is related to offspring\u2019s immune responses and atopy risk. Allergy 66, 1065\u20131074, doi: 10.1111\/j.1398-9995.2011.02587.x (2011).","journal-title":"Allergy"},{"key":"BFsrep28616_CR17","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1097\/01.psy.0000151491.80178.78","volume":"67","author":"H Fliege","year":"2005","unstructured":"Fliege, H. et al. The Perceived Stress Questionnaire (PSQ) reconsidered: validation and reference values from different clinical and healthy adult samples. Psychosomatic Medicine 67, 78\u201388, doi: 10.1097\/01.psy.0000151491.80178.78 (2005).","journal-title":"Psychosomatic Medicine"},{"key":"BFsrep28616_CR18","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/0022-3999(93)90120-5","volume":"37","author":"S Levenstein","year":"1993","unstructured":"Levenstein, S. et al. Development of the Perceived Stress Questionnaire: a new tool for psychosomatic research. Journal of Psychosomatic Research 37, 19\u201332 (1993).","journal-title":"Journal of Psychosomatic Research"},{"key":"BFsrep28616_CR19","doi-asserted-by":"publisher","first-page":"856","DOI":"10.2466\/pr0.1989.64.3.856","volume":"64","author":"M Rauste-von Wright","year":"1989","unstructured":"Rauste-von Wright, M. & Frankenhaeuser, M. Females\u2019 emotionality as reflected in the excretion of the dopamine metabolite HVA during mental stress. Psychological Reports 64, 856\u2013858, doi: 10.2466\/pr0.1989.64.3.856 (1989).","journal-title":"Psychological Reports"},{"key":"BFsrep28616_CR20","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1542\/peds.79.2.203","volume":"79","author":"M Tuchman","year":"1987","unstructured":"Tuchman, M., Ramnaraine, M. L., Woods, W. G. & Krivit, W. Three years of experience with random urinary homovanillic and vanillylmandelic acid levels in the diagnosis of neuroblastoma. Pediatrics 79, 203\u2013205 (1987).","journal-title":"Pediatrics"},{"key":"BFsrep28616_CR21","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.jchromb.2015.06.021","volume":"998\u2013999","author":"D Remane","year":"2015","unstructured":"Remane, D. et al. Validation of a multi-analyte HPLC-DAD method for determination of uric acid, creatinine, homovanillic acid, niacinamide, hippuric acid, indole-3-acetic acid and 2-methylhippuric acid in human urine. J Chromatogr B Analyt Technol Biomed Life Sci 998\u2013999, 40\u201344, doi: 10.1016\/j.jchromb.2015.06.021 (2015).","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"BFsrep28616_CR22","doi-asserted-by":"crossref","unstructured":"Junge, K. M. et al. Increased vitamin D levels at birth and in early infancy increase offspring allergy risk-evidence for involvement of epigenetic mechanisms. The Journal of Allergy and Clinical Immunology, doi: 10.1016\/j.jaci.2015.06.040 (2015).","DOI":"10.1016\/j.jaci.2015.06.040"},{"key":"BFsrep28616_CR23","doi-asserted-by":"publisher","first-page":"R83","DOI":"10.1186\/gb-2012-13-10-r83","volume":"13","author":"KD Hansen","year":"2012","unstructured":"Hansen, K. D., Langmead, B. & Irizarry, R. A. BSmooth: from whole genome bisulfite sequencing reads to differentially methylated regions. Genome Biol 13, R83, doi: 10.1186\/gb-2012-13-10-r83 (2012).","journal-title":"Genome Biol"},{"key":"BFsrep28616_CR24","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1093\/ije\/dyr238","volume":"41","author":"AE Jaffe","year":"2012","unstructured":"Jaffe, A. E. et al. Bump hunting to identify differentially methylated regions in epigenetic epidemiology studies. Int J Epidemiol 41, 200\u2013209, doi: 10.1093\/ije\/dyr238 (2012).","journal-title":"Int J Epidemiol"},{"key":"BFsrep28616_CR25","doi-asserted-by":"publisher","first-page":"324","DOI":"10.3389\/fgene.2014.00324","volume":"5","author":"MD Robinson","year":"2014","unstructured":"Robinson, M. D. et al. Statistical methods for detecting differentially methylated loci and regions. Front Genet 5, 324, doi: 10.3389\/fgene.2014.00324 (2014).","journal-title":"Front Genet"},{"key":"BFsrep28616_CR26","doi-asserted-by":"publisher","first-page":"15785","DOI":"10.1073\/pnas.0507816102","volume":"102","author":"M Ehrich","year":"2005","unstructured":"Ehrich, M. et al. Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. Proceedings of the National Academy of Sciences of the United States of America 102, 15785\u201315790, doi: 10.1073\/pnas.0507816102 (2005).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep28616_CR27","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.envint.2014.08.013","volume":"73","author":"U Franck","year":"2014","unstructured":"Franck, U. et al. Prenatal VOC exposure and redecoration are related to wheezing in early infancy. Environment International 73, 393\u2013401, doi: 10.1016\/j.envint.2014.08.013 (2014).","journal-title":"Environment International"},{"key":"BFsrep28616_CR28","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1002\/dta.1767","volume":"7","author":"H Hoeke","year":"2015","unstructured":"Hoeke, H. et al. Monitoring of drug intake during pregnancy by questionnaires and LC-MS\/MS drug urine screening: evaluation of both monitoring methods. Drug Testing and Analysis 7, 695\u2013702, doi: 10.1002\/dta.1767 (2015).","journal-title":"Drug Testing and Analysis"},{"key":"BFsrep28616_CR29","doi-asserted-by":"publisher","first-page":"e00523","DOI":"10.7554\/eLife.00523","volume":"2","author":"M Gutierrez-Arcelus","year":"2013","unstructured":"Gutierrez-Arcelus, M. et al. Passive and active DNA methylation and the interplay with genetic variation in gene regulation. eLife 2, e00523, doi: 10.7554\/eLife.00523 (2013).","journal-title":"eLife"},{"key":"BFsrep28616_CR30","doi-asserted-by":"publisher","first-page":"R61","DOI":"10.1186\/gb-2012-13-7-r61","volume":"13","author":"Y Liu","year":"2012","unstructured":"Liu, Y., Siegmund, K. D., Laird, P. W. & Berman, B. P. Bis-SNP: combined DNA methylation and SNP calling for Bisulfite-seq data. Genome Biol 13, R61, doi: 10.1186\/gb-2012-13-7-r61 (2012).","journal-title":"Genome Biol"},{"key":"BFsrep28616_CR31","doi-asserted-by":"publisher","first-page":"861","DOI":"10.15252\/msb.20156520","volume":"12","author":"T Bauer","year":"2016","unstructured":"Bauer, T. et al. Environment-induced epigenetic reprogramming in genomic regulatory elements in smoking mothers and their children. Molecular Systems Biology 12, 861, doi: 10.15252\/msb.20156520 (2016).","journal-title":"Molecular Systems Biology"},{"key":"BFsrep28616_CR32","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nature14248","volume":"518","author":"C Roadmap Epigenomics","year":"2015","unstructured":"Roadmap Epigenomics, C. et al. Integrative analysis of 111 reference human epigenomes. Nature 518, 317\u2013330, doi: 10.1038\/nature14248 (2015).","journal-title":"Nature"},{"key":"BFsrep28616_CR33","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature11247","volume":"489","author":"EP Consortium","year":"2012","unstructured":"Consortium, E. P. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57\u201374, doi: 10.1038\/nature11247 (2012).","journal-title":"Nature"},{"key":"BFsrep28616_CR34","doi-asserted-by":"publisher","first-page":"D56","DOI":"10.1093\/nar\/gks1172","volume":"41","author":"KR Rosenbloom","year":"2013","unstructured":"Rosenbloom, K. R. et al. ENCODE data in the UCSC Genome Browser: year 5 update. Nucleic Acids Research 41, D56\u201363, doi: 10.1093\/nar\/gks1172 (2013).","journal-title":"Nucleic Acids Research"},{"key":"BFsrep28616_CR35","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1465-9921-7-15","volume":"7","author":"JE Pongracz","year":"2006","unstructured":"Pongracz, J. E. & Stockley, R. A. Wnt signalling in lung development and diseases. Respiratory Research 7, 15, doi: 10.1186\/1465-9921-7-15 (2006).","journal-title":"Respiratory Research"},{"key":"BFsrep28616_CR36","doi-asserted-by":"publisher","first-page":"e80294","DOI":"10.1371\/journal.pone.0080294","volume":"8","author":"SC Brennan","year":"2013","unstructured":"Brennan, S. C. et al. Fetal calcium regulates branching morphogenesis in the developing human and mouse lung: involvement of voltage-gated calcium channels. PloS one 8, e80294, doi: 10.1371\/journal.pone.0080294 (2013).","journal-title":"PloS one"},{"key":"BFsrep28616_CR37","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.bbrc.2004.08.058","volume":"323","author":"EL Thompson","year":"2004","unstructured":"Thompson, E. L. et al. Chronic administration of NMU into the paraventricular nucleus stimulates the HPA axis but does not influence food intake or body weight. Biochemical and Biophysical Research Communications 323, 65\u201371, doi: 10.1016\/j.bbrc.2004.08.058 (2004).","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"BFsrep28616_CR38","doi-asserted-by":"publisher","first-page":"156","DOI":"10.3389\/fendo.2012.00156","volume":"3","author":"LK Malendowicz","year":"2012","unstructured":"Malendowicz, L. K., Ziolkowska, A. & Rucinski, M. Neuromedins U and S involvement in the regulation of the hypothalamo-pituitary-adrenal axis. Frontiers in Endocrinology 3, 156, doi: 10.3389\/fendo.2012.00156 (2012).","journal-title":"Frontiers in Endocrinology"},{"key":"BFsrep28616_CR39","doi-asserted-by":"publisher","first-page":"7230","DOI":"10.4049\/jimmunol.173.12.7230","volume":"173","author":"EN Johnson","year":"2004","unstructured":"Johnson, E. N. et al. Neuromedin U elicits cytokine release in murine Th2-type T cell clone D10.G4.1. Journal of imMunology 173, 7230\u20137238 (2004).","journal-title":"Journal of imMunology"},{"key":"BFsrep28616_CR40","doi-asserted-by":"crossref","unstructured":"Su, Q. et al. Maternal Stress in Gestation: Birth Outcomes and Stress-Related Hormone Response of the Neonates. Pediatrics and Neonatology, doi: 10.1016\/j.pedneo.2015.02.002 (2015).","DOI":"10.1016\/j.pedneo.2015.02.002"},{"key":"BFsrep28616_CR41","doi-asserted-by":"publisher","first-page":"570541","DOI":"10.1155\/2015\/570541","volume":"2015","author":"KN Dancause","year":"2015","unstructured":"Dancause, K. N. et al. Prenatal stress due to a natural disaster predicts adiposity in childhood: the Iowa Flood Study. J Obes 2015, 570541, doi: 10.1155\/2015\/570541 (2015).","journal-title":"J Obes"},{"key":"BFsrep28616_CR42","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1007\/s10803-007-0414-0","volume":"38","author":"D Kinney","year":"2008","unstructured":"Kinney, D., Miller, A., Crowley, D., Huang, E. & Gerber, E. Autism Prevalence Following Prenatal Exposure to Hurricanes and Tropical Storms in Louisiana. J Autism Dev Disord 38, 481\u2013488, doi: 10.1007\/s10803-007-0414-0 (2008).","journal-title":"J Autism Dev Disord"},{"key":"BFsrep28616_CR43","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.psychres.2014.04.034","volume":"219","author":"DJ Walder","year":"2014","unstructured":"Walder, D. J. et al. Prenatal maternal stress predicts autism traits in 6(1\/2) year-old children: Project Ice Storm. Psychiatry Research 219, 353\u2013360, doi: 10.1016\/j.psychres.2014.04.034 (2014).","journal-title":"Psychiatry Research"},{"key":"BFsrep28616_CR44","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.neubiorev.2014.12.003","volume":"49","author":"M Debnath","year":"2015","unstructured":"Debnath, M., Venkatasubramanian, G. & Berk, M. Fetal programming of schizophrenia: select mechanisms. Neuroscience and Biobehavioral reviews 49, 90\u2013104, doi: 10.1016\/j.neubiorev.2014.12.003 (2015).","journal-title":"Neuroscience and Biobehavioral reviews"},{"key":"BFsrep28616_CR45","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, T. G. & O\u2019Donnell, K. Prenatal stress and the programming of the HPA axis. Neuroscience and Biobehavioral reviews 35, 17\u201322, doi: 10.1016\/j.neubiorev.2009.11.008 (2010).","journal-title":"Neuroscience and Biobehavioral reviews"},{"key":"BFsrep28616_CR46","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3389\/neuro.08.019.2009","volume":"3","author":"EC Cottrell","year":"2009","unstructured":"Cottrell, E. C. & Seckl, J. R. Prenatal stress, glucocorticoids and the programming of adult disease. Front Behav Neurosci 3, 19, doi: 10.3389\/neuro.08.019.2009 (2009).","journal-title":"Front Behav Neurosci"},{"key":"BFsrep28616_CR47","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1159\/000341684","volume":"96","author":"L Paternain","year":"2012","unstructured":"Paternain, L. et al. Transcriptomic and epigenetic changes in the hypothalamus are involved in an increased susceptibility to a high-fat-sucrose diet in prenatally stressed female rats. Neuroendocrinology 96, 249\u2013260, doi: 10.1159\/000341684 (2012).","journal-title":"Neuroendocrinology"},{"key":"BFsrep28616_CR48","doi-asserted-by":"publisher","first-page":"C198","DOI":"10.1152\/ajpcell.00045.2010","volume":"300","author":"JE Campbell","year":"2011","unstructured":"Campbell, J. E., Peckett, A. J., D\u2019Souza, A. M., Hawke, T. J. & Riddell, M. C. Adipogenic and lipolytic effects of chronic glucocorticoid exposure. American Journal of Physiology. Cell Physiology 300, C198\u2013209, doi: 10.1152\/ajpcell.00045.2010 (2011).","journal-title":"American Journal of Physiology. Cell Physiology"},{"key":"BFsrep28616_CR49","doi-asserted-by":"crossref","unstructured":"Sternthal, M. J., Coull, B. A., Chiu, Y. H., Cohen, S. & Wright, R. J. Associations among maternal childhood socioeconomic status, cord blood IgE levels, and repeated wheeze in urban children. The Journal of Allergy and Clinical Immunology 128, 337\u2013345 e331, doi: 10.1016\/j.jaci.2011.05.008 (2011).","DOI":"10.1016\/j.jaci.2011.05.008"},{"key":"BFsrep28616_CR50","doi-asserted-by":"crossref","unstructured":"Chiu, Y. H. et al. Effects of prenatal community violence and ambient air pollution on childhood wheeze in an urban population. The Journal of Allergy and Clinical Immunology 133, 713\u2013722 e714, doi: 10.1016\/j.jaci.2013.09.023 (2014).","DOI":"10.1016\/j.jaci.2013.09.023"},{"key":"BFsrep28616_CR51","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1164\/rccm.200904-0637OC","volume":"182","author":"RJ Wright","year":"2010","unstructured":"Wright, R. J. et al. Prenatal maternal stress and cord blood innate and adaptive cytokine responses in an inner-city cohort. American Journal of Respiratory and Critical Care Medicine 182, 25\u201333, doi: 10.1164\/rccm.200904-0637OC (2010).","journal-title":"American Journal of Respiratory and Critical Care Medicine"},{"key":"BFsrep28616_CR52","doi-asserted-by":"crossref","unstructured":"Lange, N. E. et al. Parental psychosocial stress and asthma morbidity in Puerto Rican twins. The Journal of Allergy and Clinical Immunology 127, 734\u2013740 e731\u2013737, doi: 10.1016\/j.jaci.2010.11.010 (2011).","DOI":"10.1016\/j.jaci.2010.11.010"},{"key":"BFsrep28616_CR53","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1101\/gr.180240.114","volume":"25","author":"X Agirre","year":"2015","unstructured":"Agirre, X. et al. Whole-epigenome analysis in multiple myeloma reveals DNA hypermethylation of B cell-specific enhancers. Genome Research 25, 478\u2013487, doi: 10.1101\/gr.180240.114 (2015).","journal-title":"Genome Research"},{"key":"BFsrep28616_CR54","doi-asserted-by":"publisher","first-page":"7758","DOI":"10.1038\/ncomms8758","volume":"6","author":"A Stone","year":"2015","unstructured":"Stone, A. et al. DNA methylation of oestrogen-regulated enhancers defines endocrine sensitivity in breast cancer. Nature Communications 6, 7758, doi: 10.1038\/ncomms8758 (2015).","journal-title":"Nature Communications"},{"key":"BFsrep28616_CR55","doi-asserted-by":"publisher","first-page":"10522","DOI":"10.1073\/pnas.1120658109","volume":"109","author":"H Heyn","year":"2012","unstructured":"Heyn, H. et al. Distinct DNA methylomes of newborns and centenarians. Proceedings of the National Academy of Sciences of the United States of America 109, 10522\u201310527, doi: 10.1073\/pnas.1120658109 (2012).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep28616_CR56","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/gb4033","volume":"13","author":"M Winnefeld","year":"2012","unstructured":"Winnefeld, M. & Lyko, F. The aging epigenome: DNA methylation from the cradle to the grave. Genome Biology 13, 165, doi: 10.1186\/gb4033 (2012).","journal-title":"Genome Biology"},{"key":"BFsrep28616_CR57","doi-asserted-by":"publisher","first-page":"a001917","DOI":"10.1101\/cshperspect.a001917","volume":"2","author":"A Chedotal","year":"2010","unstructured":"Chedotal, A. & Richards, L. J. Wiring the brain: the biology of neuronal guidance. Cold Spring Harbor Perspectives in Biology 2, a001917, doi: 10.1101\/cshperspect.a001917 (2010).","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"BFsrep28616_CR58","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1196\/annals.1314.006","volume":"1032","author":"JR Seckl","year":"2004","unstructured":"Seckl, J. R. & Meaney, M. J. Glucocorticoid programming. Annals of the New York Academy of Sciences 1032, 63\u201384, doi: 10.1196\/annals.1314.006 (2004).","journal-title":"Annals of the New York Academy of Sciences"},{"key":"BFsrep28616_CR59","doi-asserted-by":"crossref","unstructured":"Turecki, G. & Meaney, M. J. Effects of the Social Environment and Stress on Glucocorticoid Receptor Gene Methylation: A Systematic Review. Biol Psychiatry, doi: 10.1016\/j.biopsych.2014.11.022 (2014).","DOI":"10.1016\/j.biopsych.2014.11.022"},{"key":"BFsrep28616_CR60","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.neubiorev.2015.05.016","volume":"55","author":"H Palma-Gudiel","year":"2015","unstructured":"Palma-Gudiel, H., Cordova-Palomera, A., Leza, J. C. & Fananas, L. Glucocorticoid receptor gene (NR3C1) methylation processes as mediators of early adversity in stress-related disorders causality: A critical review. Neuroscience and Biobehavioral Reviews 55, 520\u2013535, doi: 10.1016\/j.neubiorev.2015.05.016 (2015).","journal-title":"Neuroscience and Biobehavioral Reviews"},{"key":"BFsrep28616_CR61","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.psyneuen.2015.04.012","volume":"58","author":"LJ van der Knaap","year":"2015","unstructured":"van der Knaap, L. J., Oldehinkel, A. J., Verhulst, F. C., van Oort, F. V. & Riese, H. Glucocorticoid receptor gene methylation and HPA-axis regulation in adolescents. The TRAILS study. Psychoneuroendocrinology 58, 46\u201350, doi: 10.1016\/j.psyneuen.2015.04.012 (2015).","journal-title":"Psychoneuroendocrinology"},{"key":"BFsrep28616_CR62","doi-asserted-by":"publisher","first-page":"334","DOI":"10.3109\/15622975.2013.866693","volume":"15","author":"N Perroud","year":"2014","unstructured":"Perroud, N. et al. The Tutsi genocide and transgenerational transmission of maternal stress: epigenetics and biology of the HPA axis. World J Biol Psychiatry 15, 334\u2013345, doi: 10.3109\/15622975.2013.866693 (2014).","journal-title":"World J Biol Psychiatry"},{"key":"BFsrep28616_CR63","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1016\/j.biopsych.2014.02.006","volume":"77","author":"R Yehuda","year":"2015","unstructured":"Yehuda, R. et al. Lower methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of veterans with posttraumatic stress disorder. Biol Psychiatry 77, 356\u2013364, doi: 10.1016\/j.biopsych.2014.02.006 (2015).","journal-title":"Biol Psychiatry"},{"key":"BFsrep28616_CR64","doi-asserted-by":"publisher","first-page":"97","DOI":"10.4161\/epi.3.2.6034","volume":"3","author":"TF Oberlander","year":"2008","unstructured":"Oberlander, T. F. et al. Prenatal exposure to maternal depression, neonatal methylation of human. Epigenetics: Official Journal of the DNA Methylation Society 3, 97\u2013106 (2008).","journal-title":"Epigenetics: Official Journal of the DNA Methylation Society"},{"key":"BFsrep28616_CR65","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1016\/j.jpsychires.2013.03.009","volume":"47","author":"T Hompes","year":"2013","unstructured":"Hompes, T. et al. Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood. Journal of Psychiatric Research 47, 880\u2013891, doi: 10.1016\/j.jpsychires.2013.03.009 (2013).","journal-title":"Journal of Psychiatric Research"},{"key":"BFsrep28616_CR66","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.biopsycho.2010.01.007","volume":"84","author":"RJ Wright","year":"2010","unstructured":"Wright, R. J. Perinatal stress and early life programming of lung structure and function. Biological Psychology 84, 46\u201356, doi: 10.1016\/j.biopsycho.2010.01.007 (2010).","journal-title":"Biological Psychology"},{"key":"BFsrep28616_CR67","doi-asserted-by":"publisher","first-page":"2597","DOI":"10.1172\/JCI27331","volume":"116","author":"V Dave","year":"2006","unstructured":"Dave, V. et al. Calcineurin\/Nfat signaling is required for perinatal lung maturation and function. The Journal of Clinical Investigation 116, 2597\u20132609, doi: 10.1172\/JCI27331 (2006).","journal-title":"The Journal of Clinical Investigation"},{"key":"BFsrep28616_CR68","doi-asserted-by":"publisher","first-page":"21068","DOI":"10.1074\/jbc.M001546200","volume":"275","author":"R Fujii","year":"2000","unstructured":"Fujii, R. et al. Identification of neuromedin U as the cognate ligand of the orphan G protein-coupled receptor FM-3. The Journal of Biological Chemistry 275, 21068\u201321074, doi: 10.1074\/jbc.M001546200 (2000).","journal-title":"The Journal of Biological Chemistry"},{"key":"BFsrep28616_CR69","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1016\/j.bbrc.2006.01.075","volume":"341","author":"M Moriyama","year":"2006","unstructured":"Moriyama, M. et al. The neuropeptide neuromedin U promotes IL-6 production from macrophages and endotoxin shock. Biochemical and Biophysical Research Communications 341, 1149\u20131154, doi: 10.1016\/j.bbrc.2006.01.075 (2006).","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"BFsrep28616_CR70","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1006\/bbrc.2001.5945","volume":"289","author":"R Hanada","year":"2001","unstructured":"Hanada, R. et al. A role for neuromedin U in stress response. Biochemical and Biophysical Research Communications 289, 225\u2013228, doi: 10.1006\/bbrc.2001.5945 (2001).","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"BFsrep28616_CR71","first-page":"289","volume":"43","author":"V Klenerova","year":"1994","unstructured":"Klenerova, V. & Sida, P. Changes in beta-adrenergic receptors in the neurohypophysis and intermediate lobe of rat hypophysis exposed to stress. Physiological research\/Academia Scientiarum Bohemoslovaca 43, 289\u2013292 (1994).","journal-title":"Physiological research\/Academia Scientiarum Bohemoslovaca"},{"key":"BFsrep28616_CR72","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1124\/mol.104.002337","volume":"66","author":"PJ Brighton","year":"2004","unstructured":"Brighton, P. J., Szekeres, P. G., Wise, A. & Willars, G. B. Signaling and ligand binding by recombinant neuromedin U receptors: evidence for dual coupling to Galphaq\/11 and Galphai and an irreversible ligand-receptor interaction. Mol Pharmacol 66, 1544\u20131556, doi: 10.1124\/mol.104.002337 (2004).","journal-title":"Mol Pharmacol"},{"key":"BFsrep28616_CR73","doi-asserted-by":"publisher","first-page":"40231","DOI":"10.1074\/jbc.M305892200","volume":"278","author":"ML Mucenski","year":"2003","unstructured":"Mucenski, M. L. et al. beta-Catenin is required for specification of proximal\/distal cell fate during lung morphogenesis. The Journal of Biological Chemistry 278, 40231\u201340238, doi: 10.1074\/jbc.M305892200 (2003).","journal-title":"The Journal of Biological Chemistry"},{"key":"BFsrep28616_CR74","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1006\/dbio.2002.0729","volume":"248","author":"C Li","year":"2002","unstructured":"Li, C., Xiao, J., Hormi, K., Borok, Z. & Minoo, P. Wnt5a participates in distal lung morphogenesis. Developmental Biology 248, 68\u201381 (2002).","journal-title":"Developmental Biology"},{"key":"BFsrep28616_CR75","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.ydbio.2005.08.035","volume":"287","author":"C Li","year":"2005","unstructured":"Li, C. et al. Wnt5a regulates Shh and Fgf10 signaling during lung development. Dev Biol 287, 86\u201397, doi: 10.1016\/j.ydbio.2005.08.035 (2005).","journal-title":"Dev Biol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep28616.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep28616","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep28616.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T05:09:00Z","timestamp":1672895340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep28616"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,28]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,6,30]]}},"alternative-id":["BFsrep28616"],"URL":"https:\/\/doi.org\/10.1038\/srep28616","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,28]]},"assertion":[{"value":"2 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"28616"}}