Aberrant first trimester placental endothelial cell biology in fetal growth restriction

我们出生的体型应该由我们从父母那里继承的基因决定，无论许多婴儿出生时都比他们应有的尺寸小。其中一些婴儿可能在怀孕期间遭受某种形式的饥饿，无法从母亲那里获得必要的氧气和营养。人们认为，怀孕期间遭受饥饿影响的婴儿不仅在出生时更有可能出现问题，而且这些问题会伴随他们一生，造成长期的破坏性后果。较小的婴儿在以后的生活中更有可能出现健康问题，包括心血管疾病和糖尿病风险增加。据估计，仅在英国就有多达300万人受到影响，在他们的一生中，这给医疗服务带来了巨大的经济负担。为了让婴儿在怀孕期间从母亲那里获得所需的营养，它必须有一个健康的胎盘和丰富的血管网络。这个网络在怀孕早期就形成了，远远早于准确测量婴儿生长的时间。胎盘血管不能发育成这个网络是小婴儿怀孕的常见特征。在我们临床同事的帮助下，我们使用了一种名为子宫动脉多普勒超声的技术来识别可能导致小婴儿的怀孕，并发现胎盘血管与正常大小婴儿的妊娠不同。这个项目的目的是更仔细地研究这些细胞为什么不同。我们将研究形成血管的细胞生长和形成血管网络的能力。我们还将看到为什么会导致小婴儿死亡的怀孕细胞对导致他们死亡的因素更敏感。只有通过理解为什么某些妊娠的细胞是不同的，我们也许有一天才能找到处理这些差异的方法。生下大小合适的婴儿有助于他们的早期生活，但也有助于他们成年后保持更长时间的健康。

The size we are born should be determined by the genes we inherit from our parents, however many babies are born smaller than they should be. Some of these babies may suffer from a form of starvation during pregnancy, not receiving the vital oxygen and nutrients they need from their mother. It is thought that babies suffering the effects of starvation during pregnancy are not only more likely to have problems at birth but these stay with them throughout their life with long lasting and damaging consequences. Smaller babies are more likely to suffer from health problems in later life, including an increased risk of cardiovascular disease and diabetes. Estimates suggest that this affects up to 3 million individuals in the UK alone and, over their lifetime, this places a huge financial burden on health services. In order for a baby to receive the nourishment it needs from its mother during pregnancy it must have a healthy placenta with a rich network of blood vessels. This network develops early in pregnancy long before the time when an accurate measure of the baby's growth can be made. Failure of the placental blood vessels to develop into this network is a common feature of pregnancies with small babies. With the help of our clinical colleagues we have used a technique called uterine artery Doppler ultrasound to identify pregnancies that are likely to result in a small baby and have found that the placental blood vessels are different to those from pregnancies with a normal sized baby. The aim of this project is to look more closely at why these cells are different. We will look at the ability of the cells that form blood vessels to grow and form vascular networks. We will also see why cells from pregnancies that would result in small babies are more sensitive to factors that result in their death. It is only by understanding, why the cells from some pregnancies are different that we may one day be able to develop ways of managing these differences. Having babies that are born the right size will help them in early life but also help keep them healthy for longer as an adult.