Endometriosis outside the uterus: evidence from tissue comparisons and imaging
Endometriosis outside the uterus has been examined through tissue samples, cultured cells and images of lesions followed over time. The defining location is outside the uterus: tissue resembling its lining grows elsewhere. MedlinePlus identifies common sites on the ovaries and fallopian tubes, in supporting tissues and behind the uterus. These locations give the disease an anatomical definition, but they do not imply that all displaced tissue behaves exactly like the lining inside the womb. Studies comparing those compartments have recorded substantial biological differences as well as similarities.
The terms used in tissue research preserve that distinction. Eutopic endometrium occupies its usual location within the uterus; ectopic tissue occupies another site. MedlinePlus describes the external patches as implants, nodules or lesions. Its definition uses tissue like the lining, rather than requiring that an entire piece of otherwise unchanged lining has simply moved. That precision matters when comparing samples from an ovarian cyst with samples from the uterus. The anatomical categories identify where the specimens originated, while laboratory measurements investigate what happened within their cells. Location and cellular behavior are related features, but they are separate measurements.
On 23 January 2014, Yoshiaki Yamagata and colleagues published a PLOS ONE study comparing cultured stromal cells from three sources. They sampled uterine endometrium from women with endometriosis, uterine endometrium from women without it, and ovarian endometrial cysts. The initial genome-wide methylation analysis included three samples in each group. Methylation concerns chemical marks associated with gene regulation. The ovarian cyst cells separated from both uterine groups when the researchers compared these marks. By contrast, the two groups of cells taken from the uterus showed relatively few differences in that analysis.
The investigators also compared gene activity through a transcriptome analysis. That measurement did not separate the groups in the same way as methylation profiling. Some findings involving genes related to steroid production were checked by additional methods in larger sets of samples. The difference between the two analyses is substantive: one method detected a distinction that another did not clearly reproduce. The study of endometriosis outside the uterus therefore depended on the kind of molecular information collected as well as the origin of the cells. Its cultured samples represented selected cellular components, rather than every feature of an intact lesion.
A separate PLOS Genetics investigation published in March 2014 examined related differences through the GATA family of transcription factors, proteins involved in controlling gene activity. Matthew Dyson and colleagues mapped methylation and gene expression in healthy endometrial and endometriotic stromal cells. They identified extensive differences, including 42,248 differently methylated sites. Their functional experiments connected GATA2 with hormone-driven differentiation in healthy cells and found GATA6 abundant in endometriotic cells. The findings linked a broad molecular pattern with particular regulators, extending the comparison beyond a description of where the tissue had been collected.
The GATA experiments also altered gene expression in cultured cells to examine consequences. Expression of GATA6 in healthy endometrial cells reduced hormone sensitivity, suppressed GATA2 and induced markers associated with endometriosis. The authors proposed an epigenetic switch connecting those observations. That proposal concerned a mechanism supported by their cellular comparisons and experiments. It did not establish the original route by which a lesion arrived at every anatomical site. The distinction between finding a disease-related cellular state and identifying the first event that caused a person's disease remained part of the research itself.
Imaging provided a different record in a 2019 French case series. Anne Elodie Millischer and colleagues compared MRI examinations obtained before and after pregnancy in 21 women without previous endometriosis surgery. The series covered 67 deep lesions and used a consistent imaging protocol with one experienced radiologist. Average lesion volumes were lower after pregnancy. These were retrospective observations from a single referral hospital. Changes in measured volume concerned those particular lesions across the available examinations; they did not establish that pregnancy eliminated endometriosis or that a reduction in size resolved every consequence of the disease.
WHO's public health description adds the consequences that a cell culture or lesion-volume measurement cannot encompass. It identifies endometrium-like tissue outside the uterus, inflammation and scar formation, with disease most often in the pelvis but sometimes elsewhere. It also describes severe disruption of work or school, financial burdens and stigma around menstrual pain. WHO reports diagnostic delays averaging between 4 and 12 years, alongside limited access to care in many settings. It identifies normalization of pain and poor awareness among families and health workers among the continuing challenges. The cause remains unknown. Endometriosis outside the uterus has thus been documented at several levels: the position of lesions, differences between cell populations and the continuing effects on people's lives. The physical location is well established even while studies investigate how those tissues develop and persist.
- MedlinePlus, Endometriosis: anatomical definition and lesion locations — medlineplus.gov
- Yamagata and colleagues, Genome-Wide DNA Methylation Profiling in Cultured Eutopic and Ectopic Endometrial Stromal Cells, 2014 — journals.plos.org
- Dyson and colleagues, Genome-Wide DNA Methylation Analysis Predicts an Epigenetic Switch for GATA Factor Expression in Endometriosis, 2014 — journals.plos.org
- Millischer and colleagues, MRI presentation of deep endometriosis nodules before and after pregnancy, 2019 — journals.plos.org
- World Health Organization, Endometriosis: definition and public health impact — www.who.int
- MedlinePlus Medical Encyclopedia, Endometriosis: ovaries, fallopian tubes and pelvic lining — medlineplus.gov