WNT signalling in human trophectoderm development

我试图发现早期胎盘发育的过程。我们知道胎盘的正常功能对母亲和婴儿都至关重要。人类卵子受精后，细胞随着胚胎的生长而繁殖。5天后，胚胎被称为囊胚，由大约100个细胞组成。大约90%的这些细胞，被称为滋养外胚层细胞，将继续在胎盘中形成滋养细胞。早期怀孕通常被描述为一个“黑盒子”，由于难以接近发育中的胚胎，我们对控制滋养外胚层和滋养细胞发育的关键基因和信号通路知之甚少。然而，人类胚胎研究的进展和我们研究滋养细胞的体外模型现在为研究早期胎盘发育提供了机会。我研究的目的是确定对胎盘发育至关重要的信号通路。从我对人类胚泡的研究中，我发现了一条被称为“WNT信号通路”的途径，我假设它控制着滋养外胚层向滋养细胞的成熟。我将通过使用先进的成像技术来验证这一假设，以确认WNT信号在胚胎中是活跃的。我将通过使用精确的分子工具阻断其活性并检查其对细胞增殖和基因表达的影响来研究这一途径的作用。由于人类胚胎是一种有限的资源，我将利用体外模型来完善分子工具和技术，我将用于研究WNT信号，然后将其应用于胚胎。这种方法的另一个优点是加深了我们对模型和它们所代表的细胞类型之间关系的理解。这些研究将对早期人类胎盘发育产生新的见解。反过来，如果我们了解这些过程是如何在健康怀孕中起作用的，我们就可以开始了解哪些缺陷可能是怀孕并发症的基础。这一知识可以帮助理解和治疗不孕症和胎盘疾病，如先兆子痫、流产和死胎。

I seek to discover the processes that underlie early placenta development. We know that the correct functioning of the placenta is crucial for both mother and baby. After a human egg is fertilised, the cells multiply as the embryo grows. After five days the embryo is called a blastocyst and is made up of around 100 cells. Around 90% of these cells, called trophectoderm cells, will go on to form the trophoblast cells in the placenta. Early pregnancy is often described as a "black box," and due to the difficulties accessing the developing conceptus, we know very little about the key genes and signalling pathways that control the development of the trophectoderm and trophoblast. However, advances in human embryo research and the in vitro models we have to study trophoblast now open up the opportunity to investigate early placenta development. The aim of my research is to identify signalling pathways that are essential for placenta development. From my studies in the human blastocyst, I have identified a pathway called the "WNT signalling pathway" that I hypothesise controls the maturation of trophectoderm into trophoblast. I will test this hypothesis by using advanced imaging techniques to confirm that WNT signalling is active in the embryo. I will investigate the role of this pathway by blocking its activity using precise molecular tools and examining its effect on cell proliferation and gene expression. As human embryos are a limited resource, I will take advantage of in vitro models to refine the molecular tools and techniques I will use to study WNT signalling before applying them to embryos. This approach has the added advantage of deepening our understanding of the relationship between the models and the cell types they represent. These studies will yield novel insights into early human placenta development. In turn, if we understand how these processes work in healthy pregnancies we can begin to understand what defects may underlie complications of pregnancy. This knowledge could inform the understanding and treatment of infertility and placenta diseases such as preeclampsia, miscarriage, and stillbirth.