{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:23:41Z","timestamp":1789410221131,"version":"build-2803163510"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,5,13]],"date-time":"2015-05-13T00:00:00Z","timestamp":1431475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/11\/16\/29260"],"award-info":[{"award-number":["RG\/11\/16\/29260"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Experimental studies in animal models supporting protective effects on the fetus of melatonin in adverse pregnancy have prompted clinical trials in human pregnancy complicated by fetal growth restriction. However, the effects of melatonin on the fetal defense to acute hypoxia, such as that which may occur during labor, remain unknown. This translational study tested the hypothesis, in\u00a0vivo, that melatonin modulates the fetal cardiometabolic defense responses to acute hypoxia in chronically instrumented late gestation fetal sheep via alterations in fetal nitric oxide (<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>) bioavailability. Under anesthesia, 6 fetal sheep at 0.85 gestation were instrumented with vascular catheters and a Transonic flow probe around a femoral artery. Five days later, fetuses were exposed to acute hypoxia with or without melatonin treatment. Fetal blood was taken to determine blood gas and metabolic status and plasma catecholamine concentrations. Hypoxia during melatonin treatment was repeated during in\u00a0vivo <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> blockade with the <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> clamp. This technique permits blockade of de novo synthesis of <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> while compensating for the tonic production of the gas, thereby maintaining basal cardiovascular function. Melatonin suppressed the redistribution of blood flow away from peripheral circulations and the glycemic and plasma catecholamine responses to acute hypoxia. These are important components of the fetal brain sparing response to acute hypoxia. The effects of melatonin involved <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>\u2010dependent mechanisms as the responses were reverted by fetal treatment with the <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> clamp. Melatonin modulates the in vivo fetal cardiometabolic responses to acute hypoxia by increasing <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> bioavailability.<\/jats:p>","DOI":"10.1111\/jpi.12242","type":"journal-article","created":{"date-parts":[[2015,4,22]],"date-time":"2015-04-22T13:08:57Z","timestamp":1429708137000},"page":"80-90","source":"Crossref","is-referenced-by-count":47,"title":["Melatonin modulates the fetal cardiovascular defense response to acute hypoxia"],"prefix":"10.1111","volume":"59","author":[{"given":"Avnesh S.","family":"Thakor","sequence":"first","affiliation":[{"name":"Department of Physiology, Development &amp; Neuroscience University of Cambridge Cambridge UK"},{"name":"Department of Radiology Stanford University Stanford CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth J.","family":"Allison","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development &amp; Neuroscience University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youguo","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development &amp; Neuroscience University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberley J.","family":"Botting","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development &amp; Neuroscience University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ser\u00f3n\u2010Ferr\u00e9","sequence":"additional","affiliation":[{"name":"Facultad de Medicina Programa de Fisiopatolog\u00eda Instituto de Ciencias Biom\u00e9dicas Universidad de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio A.","family":"Herrera","sequence":"additional","affiliation":[{"name":"Facultad de Medicina Programa de Fisiopatolog\u00eda Instituto de Ciencias Biom\u00e9dicas Universidad de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dino A.","family":"Giussani","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development &amp; Neuroscience University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,5,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2014.06.014"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1530\/acta.0.1240233"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(02)00414-8"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2010.04.008"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12010"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1600-079X.2003.00092.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2008.00647.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12162"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2010.00813.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00407.2011"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.270934"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.07.010"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2013-004141"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000240877"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(74)90587-0"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0965539500000954"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019521"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1975.sp010960"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00504.2006"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.196402"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/152308603764816541"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031017"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.264275"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000080323.40820.A1"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000033827.48974.C8"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.562546"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200005000-00021"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2001.310106.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2004.00142.x"},{"key":"e_1_2_7_31_1","first-page":"CD001520","article-title":"Melatonin for preventing and treating jet lag","author":"Herxheimer A","year":"2001","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.015693"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.300.6719.230"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2009.00671.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2014.04.007"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00211.2012"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12121"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12141"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/283180"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jash.2014.01.009"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2013.152"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.258210"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009250"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms14035380"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)00112-5"},{"key":"e_1_2_7_46_1","first-page":"232","article-title":"Impact of maternal melatonin suppression on amount and functionality of brown adipose tissue (BAT) in the newborn sheep","volume":"5","author":"Seron\u2010Ferre M","year":"2014","journal-title":"Front Endocrinol"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(97)00401-9"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1254\/jjp.81.29"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1159\/000139083"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.1994.tb00095.x"},{"key":"e_1_2_7_51_1","first-page":"R1130","article-title":"Metabolic adaptation of fetal hindlimb to severe, nonlethal hypoxia","volume":"263","author":"Boyle DW","year":"1992","journal-title":"Am J Physiol"},{"key":"e_1_2_7_52_1","first-page":"223","article-title":"The effects of hypoxia on glucose turnover in the fetal sheep","volume":"5","author":"Jones CT","year":"1983","journal-title":"J Dev Physiol"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1071\/RD9950527"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-128-4-1812"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/newbio237117a0"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-197906000-00015"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.1998.tb00550.x"},{"key":"e_1_2_7_58_1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1093\/clinchem\/33.4.453","article-title":"Gas chromatographic\u2010mass spectrometric assay for 6\u2010hydroxymelatonin sulfate and 6\u2010hydroxymelatonin glucuronide in urine","volume":"33","author":"Francis PL","year":"1987","journal-title":"Clin Chem"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1159\/000244238"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1475-097X.1987.tb00179.x"}],"container-title":["Journal of Pineal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjpi.12242","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.12242","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jpi.12242","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.12242","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T17:45:32Z","timestamp":1696614332000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jpi.12242"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,13]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["10.1111\/jpi.12242"],"URL":"https:\/\/doi.org\/10.1111\/jpi.12242","archive":["Portico"],"relation":{},"ISSN":["0742-3098","1600-079X"],"issn-type":[{"value":"0742-3098","type":"print"},{"value":"1600-079X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,13]]}}}