{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:22:12Z","timestamp":1788916932904,"version":"build-2803163510"},"reference-count":87,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"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","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Adopting an integrative approach, by combining studies of cardiovascular function with those at cellular and molecular levels, this study investigated whether maternal treatment with melatonin protects against programmed cardiovascular dysfunction in the offspring using an established rodent model of hypoxic pregnancy. Wistar rats were divided into normoxic (N) or hypoxic (H, 10% O<jats:sub>2<\/jats:sub>) pregnancy\u00a0\u00b1\u00a0melatonin (M) treatment (5\u00a0\u03bcg\u00b7ml<jats:sup>\u22121<\/jats:sup>.day<jats:sup>\u22121<\/jats:sup>) in the maternal drinking water. Hypoxia\u00a0\u00b1\u00a0melatonin treatment was from day 15\u201320 of gestation (term is <jats:italic>ca<\/jats:italic>. 22\u00a0days). To control for possible effects of maternal hypoxia\u2010induced reductions in maternal food intake, additional dams underwent pregnancy under normoxic conditions but were pair\u2010fed (PF) to the daily amount consumed by hypoxic dams from day 15 of gestation. In one cohort of animals from each experimental group (N, NM, H, HM, PF, PFM), measurements were made at the end of gestation. In another, following delivery of the offspring, investigations were made at adulthood. In both fetal and adult offspring, fixed aorta and hearts were studied stereologically and frozen hearts were processed for molecular studies. In adult offspring, mesenteric vessels were isolated and vascular reactivity determined by <jats:italic>in<\/jats:italic>\u2010<jats:italic>vitro<\/jats:italic> wire myography. Melatonin treatment during normoxic, hypoxic or pair\u2010fed pregnancy elevated circulating plasma melatonin in the pregnant dam and fetus. Relative to normoxic pregnancy, hypoxic pregnancy increased fetal haematocrit, promoted asymmetric fetal growth restriction and resulted in accelerated postnatal catch\u2010up growth. Whilst fetal offspring of hypoxic pregnancy showed aortic wall thickening, adult offspring of hypoxic pregnancy showed dilated cardiomyopathy. Similarly, whilst cardiac protein expression of eNOS was downregulated in the fetal heart, eNOS protein expression was elevated in the heart of adult offspring of hypoxic pregnancy. Adult offspring of hypoxic pregnancy further showed enhanced mesenteric vasoconstrictor reactivity to phenylephrine and the thromboxane mimetic U46619. The effects of hypoxic pregnancy on cardiovascular remodelling and function in the fetal and adult offspring were independent of hypoxia\u2010induced reductions in maternal food intake. Conversely, the effects of hypoxic pregnancy on fetal and postanal growth were similar in pair\u2010fed pregnancies. Whilst maternal treatment of normoxic or pair\u2010fed pregnancies with melatonin on the offspring cardiovascular system was unremarkable, treatment of hypoxic pregnancies with melatonin in doses lower than those recommended for overcoming jet lag in humans enhanced fetal cardiac eNOS expression and prevented all alterations in cardiovascular structure and function in fetal and adult offspring. Therefore, the data support that melatonin is a potential therapeutic target for clinical intervention against developmental origins of cardiovascular dysfunction in pregnancy complicated by chronic fetal hypoxia.<\/jats:p>","DOI":"10.1111\/jpi.12766","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T18:47:52Z","timestamp":1633978072000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Maternal melatonin: Effective intervention against developmental programming of cardiovascular dysfunction in adult offspring of complicated pregnancy"],"prefix":"10.1111","volume":"72","author":[{"given":"Jeremy A.","family":"Hansell","sequence":"first","affiliation":[{"name":"Department of Physiology Development and Neuroscience University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7224-9388","authenticated-orcid":false,"given":"Hans G.","family":"Richter","sequence":"additional","affiliation":[{"name":"Facultad de Medicina Instituto de Anatom\u00eda, Histolog\u00eda y Patolog\u00eda Universidad Austral de Chile Valdivia Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J.","family":"Camm","sequence":"additional","affiliation":[{"name":"Department of Physiology Development and Neuroscience University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6342-085X","authenticated-orcid":false,"given":"Emilio A.","family":"Herrera","sequence":"additional","affiliation":[{"name":"Programa de Fisiopatolog\u00eda Facultad de Medicina Instituto de Ciencias Biom\u00e9dicas (ICBM) Universidad de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos E.","family":"Blanco","sequence":"additional","affiliation":[{"name":"National Children\u2019s Research Centre Our Lady\u2019s Children\u2019s Hospital Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Villamor","sequence":"additional","affiliation":[{"name":"Department of Pediatrics School for Oncology and Developmental Biology (GROW) Maastricht University Medical Center (MUMC+) Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga V.","family":"Patey","sequence":"additional","affiliation":[{"name":"Department of Physiology Development and Neuroscience University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3594-1455","authenticated-orcid":false,"given":"Mitchell C.","family":"Lock","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences Manchester Academic Health Science Centre University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2770-445X","authenticated-orcid":false,"given":"Andrew W.","family":"Trafford","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences Manchester Academic Health Science Centre University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina L. 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