Why researching endometriosis matters

PhD student and Digital Intern, Magda Mareckova, writes about endometriosis and her research. Read her article shortlisted for the Max Perutz Science Writing Award.

Read time: 6 minutes
A fluorescently labelled cross-section of the human endometrium
Magda Mareckova

Science and research are here for everyone – to help improve our lives and understand the world around us. Unfortunately, much of what researchers do is written in a way that is not readily accessible to everyone. Funding agencies, such as the Medical Research Council (MRC), recognise the importance of science communication and encourage the researchers they fund to start thinking about good science writing early on in their careers.

Each year, the MRC organises the Max Perutz Science Writing Award for doctoral researchers. The award is named in honour of Max Perutz, an outstanding scientist and communicator. He was awarded the 1962 Nobel Prize in Chemistry and gave one of the CHRISTMAS LECTURES in the 1980 series, The Chicken, the Egg and the Molecules. Max inspired many students to use everyday language to share their work with the people whose lives could benefit from it. For 22 years, the MRC has been asking its students to do the same – to explain why your research matters.

This year, I took part in the competition with an article explaining my research project looking at endometriosis. Endometriosis is as common as diabetes, yet the disease is poorly understood and not many people have heard about it before – a good example of why more communication is needed. My article was among the 12 shortlisted ones and you can read it below.

Photograph of The shortlisted entrants at the MRC Max Perutz Science Writing Awards ceremony.
Credit: Jon Barlow for the Medical Research Council

One in ten women suffers from endometriosis – can studying the endometrium cell by cell help us diagnose it?

Imagine you would suffer from pain that feels like razor blades inside your abdomen. It feels like being cut and burnt from within. You cannot go to school or work for 3-4 days. Each month. The pain really drains you, both physically and mentally. Painkillers do not help. You slowly stop being able to carry out your daily activities and interact with your family and friends. On top of it all, your periods are so heavy, that it becomes challenging to be away from home.

The pain and suffering goes on for years. You think your symptoms are normal. Everybody says that periods can be painful, so you just deal with it. However, the pain keeps getting worse. Roughly 7.5 years after the onset of your symptoms, you finally see a specialist. They mention ‘ENDOMETRIOSIS’ for the first time and you wonder what it is.

Endometriosis is a gynaecological disease. It affects around 10% of women in their reproductive years. Having endometriosis means having tissue that resembles the one of the lining of the womb, the endometrium, outside of the womb. The endometriosis tissue attaches to the lining of the abdomen and any organs inside your belly, where it forms the so called lesions. The lesions respond to hormonal changes across the menstrual cycle. The lesions grow, shed and bleed, just like the endometrium does. However, the shed lesion tissue cannot get out of the abdomen, it stays trapped there. The presence of this tissue causes inflammation that irritates the nerves, generating excruciating pain.

Even though endometriosis affects around 190 million women worldwide, the disease is poorly understood. We do not understand what causes endometriosis, the only way to confidently diagnose it is by performing an invasive surgery, and currently there is no cure for endometriosis either. This is when my research project comes in. The overall goal is to reduce the suffering of women with endometriosis, by reducing the time it takes to be diagnosed. More specifically, my work aims to find cues for developing a non-invasive way of diagnosing endometriosis.

To achieve my aims, I study the endometrium one cell at a time. For me, each cell is unique and important and plays a crucial role in the normal functioning of the endometrium. Why do I care so much about the endometrium and not the lesion tissue?

Cells in culture growing in the shape of a uterus
Credit: Magda Mareckova

It is about how the endometrium-like tissue gets into the abdomen. The most accepted theory is the one of retrograde menstruation. Simply speaking, the endometrium shed during menstruation does not leave the body through the vagina. Rather it goes up the fallopian tubes into the abdominal cavity, where the tissue attaches to the lining and organs. Surprisingly, retrograde menstruation occurs in 90% of women. Yet, only 10% of women develop endometriosis. Therefore, I think there is something about the properties of the endometrium that make it more likely to attach and make lesions inside the abdomen.

Unfortunately, not much is known about the endometrium. We know it consists of many different cell types, but we do not understand their function. To understand the endometrium better, I study endometrial ‘Pipelle’ biopsies donated by patients undergoing surgery. Pipelle biopsies are noninvasive, require no anaesthesia and cause only minimal discomfort. After receiving the biopsy, I use enzymes to digest the endometrium into single cells. Then I look at which genes are active in each individual cell, using a new and powerful method called single-cell RNA-sequencing.

So far, scientists have only studied the endometrium using ‘bulk’ RNA-sequencing. It can be best compared to tasting a smoothie. For example, a blueberry, banana & passion fruit one. When we mash all fruits together, we cannot tell what kind of fruits are in the smoothie. However, in order to be a blueberry, banana, or passion fruit, each of the fruits have a different set of genes activated.

In single-cell RNA-sequencing we look at each individual cell separately. It is more like tasting a fruit salad! We can tell exactly what kind of cells (fruits) there are in the endometrium, what they do and how they behave. Moreover, we might even discover that in the ‘endometrial smoothie’ there are also papayas (new cell type) that we had no idea about.

Studying the endometrium cell by cell in both healthy women and those with endometriosis, I hope to uncover an endometriosis-specific signature, which would allow us to develop a non-invasive way of diagnosing endometriosis early on. Early treatment means improved quality of life for millions of women! I believe no one deserves to suffer from pain that can sometimes be worse than giving birth for many years.

Therefore, I keep working on my DPhil, hoping to find cues to aid endometriosis diagnosis.