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dc.contributor.authorHansell, JA
dc.contributor.authorRichter, HG
dc.contributor.authorCamm, Emily
dc.contributor.authorHerrera, EA
dc.contributor.authorBlanco, CE
dc.contributor.authorVillamor, E
dc.contributor.authorPatey, OV
dc.contributor.authorLock, MC
dc.contributor.authorTrafford, AW
dc.contributor.authorGalli, GLJ
dc.contributor.authorGiussani, Dino
dc.date.accessioned2021-10-22T19:22:47Z
dc.date.available2021-10-22T19:22:47Z
dc.date.issued2013-03
dc.date.submitted2021-06-11
dc.identifier.issn0742-3098
dc.identifier.otherjpi12766
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329786
dc.descriptionFunder: British Heart Foundation; Id: http://dx.doi.org/10.13039/501100000274
dc.description.abstractAbstract: 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% O2) pregnancy ± melatonin (M) treatment (5 μg·ml−1.day−1) in the maternal drinking water. Hypoxia ± melatonin treatment was from day 15–20 of gestation (term is ca. 22 days). To control for possible effects of maternal hypoxia‐induced reductions in maternal food intake, additional dams underwent pregnancy under normoxic conditions but were pair‐fed (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 in‐vitro wire myography. Melatonin treatment during normoxic, hypoxic or pair‐fed 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‐up 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‐induced reductions in maternal food intake. Conversely, the effects of hypoxic pregnancy on fetal and postanal growth were similar in pair‐fed pregnancies. Whilst maternal treatment of normoxic or pair‐fed 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.
dc.languageen
dc.subjectORIGINAL ARTICLE
dc.subjectORIGINAL ARTICLES
dc.subjectcardiovascular
dc.subjectfetal programming
dc.subjecthypoxia
dc.subjectIUGR
dc.subjectmelatonin
dc.titleMaternal melatonin: Effective intervention against developmental programming of cardiovascular dysfunction in adult offspring of complicated pregnancy
dc.typeArticle
dc.date.updated2021-10-22T19:22:46Z
prism.publicationNameJournal of Pineal Research
dc.identifier.doi10.17863/CAM.77231
dcterms.dateAccepted2021-08-26
rioxxterms.versionofrecord10.1111/jpi.12766
rioxxterms.versionAO
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidRichter, HG [0000-0002-7224-9388]
dc.contributor.orcidHerrera, EA [0000-0002-6342-085X]
dc.contributor.orcidLock, MC [0000-0002-3594-1455]
dc.contributor.orcidTrafford, AW [0000-0002-2770-445X]
dc.contributor.orcidGiussani, Dino [0000-0002-1308-1204]
dc.identifier.eissn1600-079X


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