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，胎盘形成了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亲流到胎儿血液，以便胎儿可以正常生长。胎盘必须转移适量的养分，因为太少会导致婴儿的生长良好，并且出生的生长比应有的要小。不良的生长是一个主要问题：许多小婴儿死亡，或者，如果生存下来，他们在儿童时期更有可能生病或残疾。由于这些婴儿的可能性增加了超重，成年后心脏病或糖尿病的可能性增加，因此对健康也有终身影响。胎盘可能无法正常工作的原因之一是当妈妈超重或肥胖生活时。这在英国越来越普遍，一半的孕妇在超重或肥胖的范围内具有体重指数。该项目旨在通过试图找到一种可以帮助胎盘做好工作的治疗方法来帮助这些妈妈为婴儿提供更好的结果。我们不知道水果和蔬菜是如何产生这种影响的，但是一个想法是，水果和蔬菜中有一些成分使胎盘工作得更好。我们以前的工作试图找出该组成部分是什么，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，在这些疾病中，意外的副作用可能会对妈妈和/或婴儿产生毁灭性的后果。因此，我们的实验表明，来自土混合的水甲粉的微小颗粒可以改变占地去术的实验室模型。我们还表明，当我们将这些西瓜颗粒提供给正常的孕妇小鼠时，胎盘的生长更好，并产生更多将营养素从妈妈转移到胎儿所需的蛋白质。我们认为，胎盘正在响应妈妈的肠道信息，因为我们的初步研究表明，西瓜颗粒会改变妈妈肠道中的“好”细菌，并减少肠道中有害的免疫细胞的数量，因此炎症较少。在这个项目中，我们将将这些西瓜颗粒送给肥胖的怀孕小鼠，并了解它们如何影响胎盘和幼犬的生长。我们还将研究肠道和胎盘之间的通信如何改变。最后，我们将看到通过用西瓜颗粒映射到肥胖女性中已知的肥胖小鼠中“拯救”肥胖小鼠的途径如何衡量孕妇试验是否是合乎逻辑的下一步。我们期望所有这些实验的数据能够使我们能够确定孕妇饮食与良好的胎盘生长和功能的联系。这将使我们能够发展并最终推荐，基于饮食和蔬菜的饮食变化，这将有助于胎盘在怀孕中更好地发挥胎儿生长的风险。此外，我们认为我们的数据对于其他从事植物性疗法（例如癌症和心血管疾病）的科学家将很有用。迫切需要防止婴儿出生太小的新方法。胎儿生长问题不仅会给单个家庭带来困扰，而且还使医院拥有昂贵的产科/新生儿护理费用，以及照顾长期健康问题的成年人的前景。社会的成年人口将使生活质量较差。预期寿命继续增加，但我们并没有健康地衰老，因为除了肥胖外，糖尿病和心血管疾病的发生率也在增加。因此，除非我们找到防止这些条件的方法，否则我们的许多额外年份将受到疾病的困扰。