Maternal Obesity During Pregnancy: Translatable Programmed Cardiovascular Dysfunction in Offspring

孕妇孕期肥胖是一个日益令人担忧的保健问题，对母亲和儿童都有短期和长期的有害后果。在2015年的年度报告中，当时担任首席医疗官的莎莉·戴维斯夫人强调，英国超过一半的女性在怀孕期间超重或肥胖。她强调，注重孕妇及其后代的健康并采取干预措施加以改善，为确保母亲和儿童的身心健康提供了一个新的重要机会。在人类中，重要的介入研究集中在肥胖或超重怀孕期间的母亲运动。然而，调查这些研究的长期结果还需要许多年的时间。因此，动物模型是必不可少的，可以为观察到的变化提供机制见解，并为人类长期的后续研究提供信息。目前的项目直接解决了这一问题，使用了一种具有良好特征的绵羊妊娠期母体肥胖模型。它将确定怀孕期间肥胖影响后代患心脏病风险的机制，并提供孕期干预措施预防这种影响的宝贵信息。与啮齿类动物（如小鼠和大鼠）出生时高度不成熟相比，绵羊和人类的胎儿心脏和血液在发育过程中使其结构和功能成熟的速度相似。因此，绵羊是解决这些问题的理想动物模型，使研究与人类临床情况更加相关。研究目标本项目将模拟人类在绵羊怀孕期间的肥胖情况，并确定母亲肥胖如何损害婴儿的心脏和循环，并增加成年后代患心脏病的风险。它将测试一种特殊的抗氧化药物，作为肥胖怀孕期间预防这种情况的潜在治疗方法。研究的潜在益处研究结果可能会导致临床药物疗法的设计，以对抗母亲肥胖对婴儿心脏和循环的不良影响，从而降低后代患心脏病的风险。心血管疾病是当今英国最大的杀手，而心血管疾病的早期起源，如怀孕期间母亲肥胖对未出生的孩子造成的影响，也促成了这一点。因此，这项工作提供了强有力的计划，旨在提供现实的潜在干预措施，以改善人口健康，改善肥胖妇女及其子女的生活质量，从而对健康产生重大的临床、经济和社会影响。

Maternal obesity during pregnancy is an increasingly alarming health care issue with short and long term detrimental consequences for both mother and child. In her 2015 annual report, then as Chief Medical Officer, Dame Sally Davies highlighted that over half of women in the UK are over-weight or obese during pregnancy. She stressed that a focus on the health of the pregnant woman and of her offspring and interventions to improve it offers a new and important opportunity to ensure the physical and mental wellbeing of mothers and children. In humans, important interventional studies have focussed on maternal exercise in obese or overweight pregnancy. However, it will take many years to investigate the long-term outcomes of these studies. Hence, animal models are indispensable to provide mechanistic insights for the changes observed and inform the human longer-term follow up studies. The current project addresses this issue directly using a well characterised sheep model of maternal obesity during pregnancy. It will define mechanisms by which obesity during pregnancy influences risk of heart disease in the offspring and provide invaluable information on what interventions during pregnancy can prevent this effect. In contrast to rodents, such as mice and rats, which are born highly immature, in sheep and humans, the foetal heart and blood mature their structure and function at similar rates during development. Therefore, sheep are the ideal animal model to address these questions and make the research more relevant to the human clinical situation.Goal of researchThis project will mimic the human situation of obesity during pregnancy in sheep and determine how maternal obesity can harm the baby's heart and circulation and increase the risk of heart disease in the adult offspring. It will test a specific antioxidant drug as potential treatment during obese pregnancy to prevent this. Potential benefit of research The results may lead to the design of clinical drug therapies to combat the ill effects of maternal obesity on the baby's heart and circulation to dimmish the risk of heart problems in the offspring. Cardiovascular disease is the greatest killer in the UK today and early origins of cardiovascular disease, such as those imposed by maternal obesity during pregnancy on the unborn child, contribute to this. Therefore, the work offers robust plans designed to deliver realistic potential interventions to improve population health and improve the quality of life not only in obese women but also their children, thereby having a major clinical, economic and societal impact on health.