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物理联系。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。胎盘必须转移适量的营养，因为太少会导致婴儿生长不好，出生时比应有的小。发育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。这对健康也有终身的影响，因为这些婴儿在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母亲超重或患有肥胖症。这在英国越来越普遍，一半的孕妇体重指数在超重或肥胖范围内。这个项目是为了帮助这些妈妈们找到一种治疗方法，帮助胎盘发挥应有的作用，从而为她们的宝宝带来更好的结果。众所周知，如果准妈妈们吃富含水果和蔬菜的饮食，胎儿的生长会更好。我们不知道水果和蔬菜是如何产生这种效果的，但有一种想法是，水果和蔬菜中有一些成分可以使胎盘更好地工作。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是一个特别好的主意，在妊娠疾病中，意想不到的副作用可能会对母亲和/或婴儿产生毁灭性的后果。到目前为止，我们的实验已经表明，来自捣碎西瓜的非常微小的颗粒可以改变胎盘的实验室模型的工作方式。我们还表明，当我们将这些西瓜颗粒给予正常怀孕的小鼠时，胎盘生长得更好，并产生更多将营养物质从母亲转移到胎儿的蛋白质。我们相信胎盘对来自妈妈肠道的信息做出了反应，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，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给怀孕的肥胖小鼠，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沟通是如何改变的。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那些已知受肥胖女性影响的通路，以衡量孕妇试验是否是合乎逻辑的下一步。我们希望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变化，这将有助于胎盘在胎儿生长不良的风险下更好地工作。此外，我们认为我们的数据将对其他科学家在其他疾病如癌症和心血管疾病的植物疗法方面的工作有用。迫切需要防止婴儿出生过小的新方法。胎儿生长问题不仅会给个别家庭带来痛苦，而且还会给医院带来昂贵的产科/新生儿护理费用，以及照顾有长期健康问题的成年人的前景。社会留下了一个生活质量较差的成年人口;预期寿命继续增加，但我们并没有健康地老龄化，因为除了肥胖，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情况的方法，否则我们的许多额外岁月将受到疾病的困扰。