Can plant-derived extracellular vesicles improve outcomes in pregnancies complicated by maternal obesity?

植物源性细胞外囊泡能否改善妊娠合并肥胖的妊娠结局？

• 批准号: MR/Y01362X/1
• 负责人: Melissa Westwood
• 金额: $ 91.68万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY01362X%2F1
• 关键词: plant; derived; extracellular; vesicles; improve

During pregnancy, the placenta forms the physical connection between a mother and her baby. One of its jobs is to transfer food and oxygen from maternal to fetal blood so that the fetus can grow properly. The placenta must transfer the right amount of nutrients because too little can cause the baby to grow less well and be born smaller than it should be. Poor growth is a major problem: many small babies die or, if they do survive, they are more likely to be ill or disabled during childhood. There's also a life-long impact on health as these infants have an increased chance of being overweight and developing heart disease or diabetes as adults. One of the reasons the placenta might not work properly is when mum is overweight or is living with obesity. This is increasingly common in the UK with half of pregnant women having a body mass index in the overweight or obese range. This project is about helping these mums to have a better outcome for their babies by trying to find a treatment that will help the placenta do its job as it should.It's already known that fetal growth is better if expectant mums eat a diet rich in fruit and vegetables. We don't know exactly how the fruit and vegetables have this effect but one idea is that there is some component within fruits and vegetables that makes the placenta work better. Our previous work has tried to find out what this component might be because a treatment based on a natural product is a particularly good idea for pregnancy disease, where unanticipated side effects could have devastating consequences for both mum and/or baby.So far, our experiments have shown that very tiny particles from mashed-up watermelons can alter the way a laboratory model of the placenta works. We've also shown that when we give these watermelon particles to normal pregnant mice, the placenta grows better and produces more of the proteins needed to transfer nutrients from mum to fetus. We believe that the placenta is responding to messages from mum's gut as our preliminary investigations have shown that the watermelon particles alter the 'good' bacteria in mum's gut and reduce the number of harmful immune cells in the gut so that there is less inflammation. In this project, we will give these watermelon particles to pregnant mice that are obese and see how they affect the placenta and the growth of the pups. We will also look at how communication between the gut and the placenta is altered. Finally, we will see how the pathways in obese mice that are 'rescued' by treatment with watermelon particles map onto those known to be affected in women living with obesity to gauge whether a trial in pregnant women would be the logical next step.We expect that the data from all of these experiments will enable us to identify what links maternal diet to good placental growth and function. This will allow us to develop and eventually recommend, dietary changes based on fruit and vegetables that will help the placenta to work better in pregnancies at risk of poor fetal growth. In addition, we think that our data will be useful to other scientists working on plant-based therapies for other conditions such as cancer and cardiovascular disease. New ways to prevent babies from being born too small are desperately needed. Not only do fetal growth problems cause distress for individual families, but they also leave hospitals with expensive obstetric/neonatal care bills and the prospect of looking after adults with long-term health problems. Society is left with an adult population that will have a poorer quality of life; life expectancy continues to increase but we are not aging healthily as in addition to obesity, the incidence of diabetes and cardiovascular disease is also increasing. So unless we find ways to prevent these conditions, many of our extra years will be plagued by illness.

在怀孕期间，胎盘形成母亲和婴儿之间的身体联系。它的工作之一是将食物和氧气从母体血液转移到胎儿血液中，以便胎儿能够正常生长。胎盘必须输送适量的营养物质，因为太少会导致婴儿生长不良，并且出生时比应有的要小。生长不良是一个主要问题：许多小婴儿死亡，或者即使他们存活下来，他们也更有可能在童年时期生病或残疾。这也会对健康产生终生影响，因为这些婴儿成年后超重和患心脏病或糖尿病的机会增加。胎盘可能无法正常工作的原因之一是当妈妈超重或患有肥胖症时。这种情况在英国越来越常见，一半孕妇的体重指数处于超重或肥胖范围。该项目旨在帮助这些妈妈们找到一种治疗方法，帮助胎盘发挥其应有的作用，从而帮助她们的宝宝获得更好的结果。众所周知，如果准妈妈们吃富含水果的饮食，胎儿的生长会更好和蔬菜。我们并不确切知道水果和蔬菜如何发挥这种作用，但一个想法是水果和蔬菜中的某些成分可以使胎盘发挥更好的作用。我们之前的工作试图找出这种成分可能是什么，因为基于天然产品的治疗对于妊娠疾病来说是一个特别好的主意，其中意想不到的副作用可能对妈妈和/或婴儿造成毁灭性后果。实验表明，捣碎的西瓜中的微小颗粒可以改变胎盘实验室模型的工作方式。我们还表明，当我们给正常怀孕的小鼠喂食这些西瓜颗粒时，胎盘会生长得更好，并产生更多将营养从母体转移到胎儿所需的蛋白质。我们相信胎盘正在对来自妈妈肠道的信息做出反应，因为我们的初步研究表明，西瓜颗粒改变了妈妈肠道中的“好”细菌，并减少了肠道中有害免疫细胞的数量，从而减少了炎症。在这个项目中，我们将把这些西瓜颗粒喂给肥胖的怀孕小鼠，看看它们如何影响胎盘和幼崽的生长。我们还将研究肠道和胎盘之间的通讯是如何改变的。最后，我们将看到通过西瓜颗粒治疗“拯救”的肥胖小鼠的通路如何映射到肥胖女性中已知受影响的通路，以判断在孕妇中进行试验是否是合乎逻辑的下一步。我们预计所有这些实验的数据将使我们能够确定母亲饮食与良好胎盘生长和功能之间的联系。这将使我们能够开发并最终推荐基于水果和蔬菜的饮食改变，这将有助于胎盘在面临胎儿生长不良风险的怀孕期间更好地工作。此外，我们认为我们的数据将对致力于癌症和心血管疾病等其他疾病的植物疗法的其他科学家有用。迫切需要新的方法来防止婴儿出生过小。胎儿生长问题不仅给各个家庭带来痛苦，而且还让医院承担昂贵的产科/新生儿护理费用，并且无法照顾患有长期健康问题的成年人。社会上的成年人口的生活质量会较差；预期寿命持续增加，但我们并没有健康地衰老，因为除了肥胖之外，糖尿病和心血管疾病的发病率也在增加。因此，除非我们找到预防这些疾病的方法，否则我们的许多额外岁月都将受到疾病的困扰。