Cell mapping project gives hope for new insights into endometriosis
1 Sep 2024
Scientists at the Wellcome Sanger Institute and Oxford University’s Nuffield department of women’s and reproductive health have created the most comprehensive and sophisticated map of the human endometrium yet achieved.
Part of the Human Cell Atlas project, the Human Endometrial Cell Atlas is publicly available now in interactive format. The work carried out has already suggested new enquiry lines into the study of gynaecological conditions including endometriosis.
The study of the endometrium, comprising the inner lining of the uterus, has enabled the uncovering of unique and diverse cell types and their changes during the menstrual cycle said the researchers, whose work is featured in Nature Genetics.
The endometrium’s role in supporting pregnancy if a fertilised egg is implanted makes it of particular interest. In situations where implantation does not occur, it sheds and rebuilds itself each month without scars but the dynamic nature of the tissue during the menstrual cycle, has made studying it previously difficult.
Because it covers an unprecedented variety of menstrual cycle phases, the atlas provides new intelligence on endometrium functioning that might contribute to the study of endometriosis and other conditions.
Endometriosis, which involves the growth of endometrial type cells outside the uterus, has now been identified as the second most common gynaecological condition in the UK. However, it has no identified cause or cure.
Linking to genetic variants that increase endometriosis risk, the researchers detected two types of immune cells and of stromal cells that are potentially involved.
The atlas data consists of c.626,000 cells from 121 people, including from 74 individuals with and 47 without endometriosis, obtained during natural menstrual cycles and when taking hormonal contraception.
The scientists found multiple new cell types present only during certain phases of the menstrual cycle, dependent on the hormone levels. A cellular response to hormone levels is essential for menstrual cycle progression and fertility, and these cells could present promising therapy targets for conditions linked to hormone disruption, such as fertility conditions.
The team uncovered interactions involved in the scarless regeneration of the endometrium between macrophage immune cells, stromal cells connective tissue cell, and blood vessel cells. They identified slight differences in the proportion and gene expression of some cells in samples from those study participants with endometriosis.
Combining the cellular map of the endometrium with a genome-wide association study, they highlighted four cell types that are most likely dysregulated by genetic changes. They also ascertained that particular signalling pathways between some stromal cells and structural cells which are necessary for menstrual cycle progression were dysregulated in those with endometriosis.
The study highlighted that these cell types and signalling pathways could be involved in endometriosis and might support future research investigating how genetic changes are linked to this condition.
Professor Krina Zondervan, co-senior author from the Nuffield Department of Women’s and Reproductive Health, University of Oxford, said:
“The human endometrium has been largely neglected in large-scale cellular studies of different parts of the body. Having a large single-cell human endometrial atlas, freely available, which will continue to be expanded, will enable important new research in the understanding and treatment of diseases such as endometriosis.”
Pic: Shutterstock/Design_Cells
