Endometriosis Map Shows How Hormones Impact the Condition
Detailed map of the human endometrium reveals unique cell types and interactions, offering insights into endometriosis.
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Researchers from the Wellcome Sanger Institute and the University of Oxford have created the most comprehensive map of the human endometrium across multiple phases of the menstrual cycle.
Published in Nature Genetics, the study provides insights into the cellular processes of the menstrual cycle and their potential role in conditions such as endometriosis.
Studying the endometrium
The endometrium is the inner layer of tissue that lines the uterus. It plays a vital role throughout the menstrual cycle by thickening during the luteal phase to prepare for the possible implantation of a blastocyst. If implantation does not occur, the endometrial lining breaks down and is shed during the menstrual phase. This monthly process involves complex and dynamic changes in the tissue, which makes it difficult to study. Previous research has set out to create a cellular atlas of endometrial-type epithelial cells. However, these studies included few donors and were unable to assess all stages that the endometrium goes through during the menstrual cycle.
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Subscribe for FREE“The human endometrium has been largely neglected in large-scale cellular studies of different parts of the body,” said co-senior author Dr. Krina Zondervan, head of department and professor of reproductive and genomic epidemiology at the Nuffield Department of Women’s and Reproductive Health at the University of Oxford.
Endometriosis is a chronic condition caused by the growth of endometrial-like tissue in places outside of the uterus, such as the ovaries, pelvic lining and fallopian tubes. The disease impacts roughly 190 million women around the world and can cause severe pelvic pain during periods and infertility. Despite it being so prevalent, there is currently no cure for endometriosis and its cause remains unknown.
The new study is part of the Human Cell Atlas project, a global effort attempting to create comprehensive reference maps of all human cells in the body, to aid in understanding of health and disease.
“Creating an integrated Human Endometrial Cell Atlas transforms all the data into ‘one language’ that researchers worldwide can speak. We hope that this atlas is a key stepping stone towards building a future endometrial atlas that includes information from across the entire lifespan and all health conditions,” said co-first author Dr. Luz Garcia-Alonso, a principal bioinformatician at the Wellcome Sanger Institute.
Hormone levels impact cellular response
The Endometrial Cell Atlas was generated using new data from 74 endometrial samples, combined with existing single-cell data from 47 people. In total, the atlas contains information from over 626,000 cells collected from individuals during their natural menstrual cycles and while on hormonal contraception, as well as from those with and without endometriosis.
The researchers identified multiple unreported cell types that were only present in certain phases of the menstrual cycle, dependent on hormone levels. They also uncovered interactions involved in the regeneration of the endometrium between immune cells, a type of connective tissue and blood vessel cells.
Understanding the effect of hormones on cell behavior will hopefully provide insight into conditions associated with hormone disruption, such as infertility, and may offer novel therapeutic targets.
Cell changes in endometriosis
When investigating the differences in the number of cell types in individuals with and without endometriosis, the team found no noticeable differences. However, they did identify small differences in the proportion and gene expression of some cells in those with the condition.
The researchers combined their findings with data from a large genome-wide association study, identifying four cell types that are most likely to be disrupted by genetic variants previously associated with endometriosis. They also discovered that certain signaling pathways between stromal and structural cells, which are crucial for menstrual cycle progression, were dysregulated in affected individuals.
These results could support future research that investigates how genetic changes may impact cell types and signaling pathways linked to endometriosis.
“Developing a non-invasive diagnostic test and effective treatment for this debilitating condition has been a priority for clinicians, researchers and those with endometriosis worldwide. While further research and validation is needed, our study suggests that certain cells and pathways are dysregulated in endometriosis and if replicated in additional studies, they could be potential diagnostic and therapy targets in the future,” said co-first author Dr. Magda Marečková, a postdoctoral researcher at the Nuffield Department of Women’s and Reproductive Health at the University of Oxford.
Advancing women’s health
“Having this in-depth and large-scale genomic resource on the endometrium is invaluable if we are ever going to fully understand how the endometrium functions in health and what goes wrong in conditions such as endometriosis,” said Marečková.
“Understanding the impact of hormones on the endometrium and being able to map all the changes throughout the menstrual cycle is something that has not been possible previously, and would not have been achievable without those who generously donated endometrial tissue to research. We have been able to reveal unique interactions and cells that can inform research models, investigate the possible causes of diseases and create a resource that can be used freely worldwide to help develop new therapies for those living with endometrial conditions,” said co-senior author Dr. Roser Vento-Tormo, group leader at the Wellcome Sanger Institute.
Reference: Marečková M, Garcia-Alonso L, Moullet M, et al. An integrated single-cell reference atlas of the human endometrium. Nat Genet. 2024. doi: 10.1038/s41588-024-01873-w
This article is a rework of a press release issued by the Wellcome Sanger Institute. Material has been edited for length and content.
