We now have the most detailed map ever made of the endometrium, or the inner lining of the uterus. This will significantly improve our understanding of reproductive health and common conditions such as endometriosis.
The endometrium is one of the most dynamic organs in the body. Each menstrual cycle, it thickens in preparation for pregnancy and, if a pregnancy doesn’t occur, sheds its top layer during menstruation.
Despite the endometrium’s pivotal role in reproductive health, we know very little about this tissue. “It is kind of a black box,” says at the Wellcome Sanger Institute in the UK.
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Vento-Tormo and her colleagues analysed more than 313,000 endometrial cells from 63 individuals of reproductive age to map out the organ. This included data gathered from six previously published datasets alongside that from 16 new donors. Of all the individuals studied, 30 had been diagnosed with endometriosis and 14 were using hormonal medications, either for birth control or for treating endometriosis. Samples were collected throughout the menstrual cycle.
Using a technique called single-cell sequencing, the researchers measured which genes were turned on or off in each cell. This allowed them to identify each type of cell and gain new insights into their functions. They then analysed endometrium tissue samples under a microscope to determine the location and structures of cells.
The team mapped the spread of cells across the endometrium, including how some change in response to the menstrual cycle. This revealed that the organ had even more ability to adapt than previously thought – its composition changes every four or so days, says Vento-Tormo. “It was a bit unexpected, even for us, how dynamic it was,” she says.
The researchers say they discovered previously unknown cell types, including one in the endometrium’s lower layer that changes across different stages of the menstrual cycle. This type of cell, which can form into other types of endometrial cells, may play an important role in regenerating the endometrium’s upper layer after it sheds during menstruation. This suggests impairments in these cell might contribute to heavy menstrual bleeding or other conditions where the endometrium doesn’t properly develop, says at the Feinstein Institutes for Medical Research in New York, who wasn’t involved in the study.
The atlas also yielded clues about endometriosis, a painful condition where tissues similar to those lining the uterus grow outside of it. By comparing samples from donors with endometriosis to those without it, the researchers identified subtle differences in cell-to-cell communication and function. For instance, samples from people with the condition showed impaired communication between the endometrium’s structural cells and its cells that respond to hormonal changes. This may contribute to the high levels of inflammation seen in people with the condition, says Metz. Insights such as this could lead to new treatments for endometriosis, which affects about 10 per cent of people who menstruate.
The map may improve our understanding of the causes behind infertility, too, by cluing us in to why some embryos are unable to implant in the uterine lining, says Vento-Tormo.
However, more samples from additional donors are needed to fully grasp the endometrium’s complexity, especially the ways it transforms with age or during menstruation, says Metz. Still, the atlas offers a crucial foundation for future research. “I think this map is going to contribute immensely in the coming years to understanding conditions that affect the endometrium,” she says.
Nature Genetics
