Medicine has a debt in the study of women’s health and the advance of technology is helping to pay it off. An international team of scientists has published the most detailed cellular map of the endometrium, the inner layer of tissue that lines the uterus, using advanced molecular biology and machine learning techniques. This achievement, whose results are published in the journal Nature. published in the magazine Nature Geneticscould provide some clues in the investigation of endometriosis, a disease about which very little is known although it affects more than 190 million women worldwide.
Roser Vento-Tormo (Valencia, 37 years old) works in the Wellcome Sanger Institute from the United Kingdom, is one of the scientists who signed the publication and explains that there are several reasons why the study of the endometrium is “historically postponed”. One of them, the main one, is that “generally little money is invested in everything that has to do with women’s health”, she says. Another is that the endometrium is one of the most dynamic and complex systems of the human body, so studying it involves several challenges. “It is a tissue that changes its composition every five days and regenerates itself entirely every month perfectly and without scars”, she says. During the menstrual cycle, the endometrium thickens and prepares the uterus for a possible pregnancy; if this does not occur, the new tissue is shed and comes out through menstruation. This process depends on millions of cells that change their identity and function depending on the type of hormone they interact with at each moment of the cycle, affecting not only their own characteristics, but also those of other cells, which generates a chain effect that is difficult for scientists to track.
The new map works like a compass. “It was like creating a Google Maps of the endometrium, with which we can know where each cell is, what it is made of and what type of interaction it has with the cells that surround it,” explains Vento-Torno. To achieve this, the scientists used single-cell sequencing, a technique that allows the genetic material of RNA to be analyzed cell by cell. “It is like having a passport for each unit in which you can read its composition, what function it performs within the body and what it can do on a large scale when it interacts with other cells,” explains the author.
This tool is particularly useful for studying the endometrium because it allows us to observe how the cells change their identity over time and how they affect the development of abnormalities such as endometriosis. In this disease, the cells of the endometrium leave the uterus and develop tissue outside it – such as in the ovaries or fallopian tubes – which in most cases causes cysts and chronic inflammation that manifests itself in disabling abdominal pain and other complications, including infertility.
In the study, scientists analyzed more than 313,000 endometrial cells collected from 63 individuals of reproductive age. The samples were obtained from participants in previous studies, with 16 new donors joining. Of the total participants, 30 had endometriosis and 14 were using hormonal medications, either for birth control or to treat the disease. Hormones, along with anti-inflammatory drugs, are the two most common ways medicine currently combats symptoms. Endometriosis, as of yet, has no cure.
A common vocabulary
The map will help scientists better understand the female reproductive system and thus develop personalized treatments that respect the needs of each patient. “What we produced was a common vocabulary to integrate all the endometrium data that exists and that will be produced in the future,” says Vento-Torno. “This study is nice because we connected what was disconnected,” she adds. Estela Lorenzo, a specialist in the Endometriosis Unit at the Hospital 12 de Octubre in Madrid, believes that this type of primary research study is a fundamental building block in the construction of scientific knowledge. “The medical revolution in women’s health has to come through this type of exploration,” she says. The atlas goes a step further than previous publications, adds the expert, because “it talks not only about the type of cells that make up the endometrium, but also about how they develop within one of the most peculiar and curious tissues of the human body.”
Francisco Carmona, a gynecologist specializing in endometriosis and president of the Spanish Society for the Study of Fibroids and Endometriosis, has spent decades investigating behind the scenes of the disease and is optimistic about the publication of the new map. “For those of us who work in the clinic, this research is a bit far away, but in the future it will be a tool from which a lot of new knowledge can be generated,” he says. For doctors, the endometrium is a puzzle of ten thousand pieces. “Now, at least, medicine has a common model for everyone to try to put this puzzle together.” Research is, in short, a tool that “opens many doors” and on which to build answers. Although the road will be long.
The next step will be to expand the sample of patients in order to expand the map and better understand each of their neighborhoods and avenues. What scientists are looking for is to detect how the different types of cells influence the correct functioning of the endometrium, which is composed of structural cells and microenvironmental cells, which are those of the immune system and those that respond to the chemical signals of hormones. One finding is that these microenvironmental cells in patients with endometriosis seem to be more important than the structural cells. Vento-Torno explains: “Most of the changes in sick people occur in these secondary cells that, in theory, are there to provide support. By not providing support, they do not give the correct signals to the structural cells and end up affecting their function.”
The endometrium map is part of the Human Cell Atlasan international initiative that aims to create a cellular map of the entire human body. If successful, scientists would have a fundamental basis for diagnosing, monitoring and treating a huge variety of diseases whose treatments are currently uncertain and complex.
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