At the placenta of everything
A runner-up in our 2017 Max Perutz Science Writing Award, PhD student Lara Morley of the Leeds Institute of Cardiovascular and Metabolic Medicine describes how she’s looking for ways to treat a failing placenta, by increasing the blood supply to the baby in the womb.
With the emergency buzzer still ringing in my ears, I feel my adrenaline subside as I bring a much anticipated new life out into the world and into the arms of its anxious parents. After all, the outcome of a pregnancy has profound implications for the lives of us all; ourselves, partners, sisters and friends. But in all the excitement of welcoming a baby into the world, the vital job of the placenta is often overlooked.
A successful pregnancy relies on a finely tuned balance of hormones, the environment in the womb, and the placenta; the rich network of blood vessels that supply the baby. The placenta is the lifeline through which the baby receives blood containing oxygen and nutrients essential for survival.
Poorly functioning blood vessels within the placenta can result in fetal growth restriction, where the baby does not put on weight as expected during the pregnancy, or even stops growing. If this goes undetected, a baby can be stillborn, with a devastating effect on the whole family. Sadly, around 1 in 200 pregnancies in the UK results in stillbirth – and growth restriction is one of the commonest causes. Being born smaller than expected also increases the risk of cerebral palsy and death as a young baby. And there can be lifelong consequences, like obesity, diabetes and heart disease.
Despite all modern medical advances, in 2017 we still have no means of treating a failing placenta. So when a baby is recognised to be small, or not growing, the only option is to deliver them. This decision can rest on a knife edge – forcing us to weigh up the risks associated with prematurity against the potential for stillbirth. Having experienced this scenario all too frequently, I felt driven to research the blood vessels within the placenta, looking for ways to increase the blood supply to the baby.
My project is taking place at a specialist institute for research in Leeds, where we study blood vessel function. Blood travels around the body through a network – a bit like a series of garden hoses. Lining the vessels are endothelial cells. Their job is to control the flow of blood by narrowing or widening the vessels – like someone squeezing or loosening their grip on a hosepipe to control the flow of water. But how the endothelial cells behave is also controlled. ‘Gated’ channels regulate what goes in and out of these specialist cells. This triggers reactions that cause the blood vessels to adapt to your body’s needs. In the past, scientists have developed medications for treating high blood pressure by targeting these very channels.
The same applies to the network of blood vessels in the placenta. If the vessels are narrowed the oxygen and nutrient supply will be reduced and the baby put at risk. However, the identity of these channels in the placenta and how they work to control the endothelial cells remains a mystery.
What are these channels? How do they work? Could they be manipulated? The aim of my PhD is to explore these questions, thanks to generous support from the Medical Research Council and the Royal College of Obstetricians and Gynaecologists.
During this first year of my project I have been extracting endothelial cells from the placentas of women delivering their babies in Leeds. The cells have come either from women whose pregnancies have been affected by growth restriction, or from those with healthy placentas. I have grown cells from these two groups of women into colonies in an incubator in our laboratory.
My experiments have been looking for differences between the healthy and growth-restricted samples. I test each colony to see how they form new blood vessels and respond to blood flow forces. In the future I will be trying out new drugs to see if they improve the function of the cells and widen the blood vessels. Excitingly, I have found that a newly discovered channel is consistently present in the cells. Blocking this particular channel has a dramatic impact on how the cells perform in my experiments, suggesting that it has an important role to play.
Through understanding how channels operate within endothelial cells of the placenta, we will learn vital information about how blood flow to a baby is controlled. Being able to manipulate these channels would be a huge step towards developing treatments for a baby that is not growing.
As I write this, I am eagerly awaiting the birth of my first baby, any day now! My excitement is tinged with inevitable anxiety, but also hope- that in the future we will have more to offer women whose babies are at risk.
After I’ve given birth, I’ll take more than just a passing glance at my placenta as it’s whisked away- the undervalued organ that has performed the most special of functions.