There is a search for rescue therapy against fetal origins of cardiovascular disease in pregnancy complicated by chronic fetal hypoxia, particularly following clinical diagnosis of fetal growth restriction (FGR). 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 FGR 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 FGR diagnosis. Chick embryos were incubated under normoxia or hypoxia (14% O2) from day 1 ± 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 NO bioavailability. Melatonin treatment of the chick embryo starting at day 13 of incubation, equivalent to ca. 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.

中文翻译：

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褪黑激素可在鸡胚的缺氧发育过程中挽救心血管功能障碍。

正在寻找针对胎儿起源的妊娠期心血管疾病并发慢性胎儿缺氧的抢救疗法，特别是在临床诊断为胎儿生长受限 (FGR) 之后。褪黑激素在不良妊娠中保护胎盘；然而，褪黑激素是否能在缺氧妊娠中保护胎儿心脏和脉管系统，而与胎盘的影响无关。在 FGR 诊断后开始治疗时，褪黑激素是否可以挽救胎儿心血管功能障碍也是未知的。我们分离了褪黑激素对缺氧孵化期间鸡胚心血管系统发育的影响。我们检验了褪黑激素直接保护胎儿心血管系统不良发育的假设，并且它可以挽救 FGR 诊断后的功能障碍。从孵化的第 13 天（约 21 天）开始，在常氧或缺氧（14% O2）下培养鸡胚±褪黑激素处理（1 mg/kg/天）。缺氧鸡胚中的褪黑激素可挽救心脏收缩功能障碍、心脏收缩性和舒张性受损、心脏交感神经支配性增加以及外周循环中的内皮功能障碍。所涉及的机制包括减少氧化应激、增强抗氧化能力和恢复血管内皮生长因子表达，以及 NO 生物利用度。从孵化第 13 天开始对鸡胚进行褪黑激素处理，相当于 ca。人类妊娠 25 周的妊娠期，可挽救低氧发育过程中心血管功能障碍的早期起源。