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Melatonin protects the placenta in adverse pregnancy; however, whether melatonin protects the fetal heart and vasculature in hypoxic pregnancy independent of effects on the placenta is unknown. Whether melatonin can rescue fetal cardiovascular dysfunction when treatment commences following <jats:styled-content style=\"fixed-case\">FGR<\/jats:styled-content> diagnosis is also unknown. We isolated the effects of melatonin on the developing cardiovascular system of the chick embryo during hypoxic incubation. We tested the hypothesis that melatonin directly protects the fetal cardiovascular system in adverse development and that it can rescue dysfunction following <jats:styled-content style=\"fixed-case\">FGR<\/jats:styled-content> diagnosis. Chick embryos were incubated under normoxia or hypoxia (14% O<jats:sub>2<\/jats:sub>) from day 1 \u00b1 melatonin treatment (1 mg\/kg\/day) from day 13 of incubation (term ~21 days). Melatonin in hypoxic chick embryos rescued cardiac systolic dysfunction, impaired cardiac contractility and relaxability, increased cardiac sympathetic dominance, and endothelial dysfunction in peripheral circulations. The mechanisms involved included reduced oxidative stress, enhanced antioxidant capacity and restored vascular endothelial growth factor expression, and <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> bioavailability. Melatonin treatment of the chick embryo starting at day 13 of incubation, equivalent to <jats:italic>ca<\/jats:italic>. 25 wk of gestation in human pregnancy, rescues early origins of cardiovascular dysfunction during hypoxic development. Melatonin may be a suitable antioxidant candidate for translation to human therapy to protect the fetal cardiovascular system in adverse pregnancy.<\/jats:p>","DOI":"10.1111\/jpi.12283","type":"journal-article","created":{"date-parts":[[2015,10,7]],"date-time":"2015-10-07T13:03:47Z","timestamp":1444223027000},"page":"16-26","source":"Crossref","is-referenced-by-count":61,"title":["Melatonin rescues cardiovascular dysfunction during hypoxic development in the chick embryo"],"prefix":"10.1111","volume":"60","author":[{"given":"Nozomi","family":"Itani","sequence":"first","affiliation":[{"name":"Department of Physiology, Development and Neuroscience University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie L.","family":"Skeffington","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience University of Cambridge Cambridge 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