TY - JOUR
T1 - New concepts on the etiology of endometriosis
AU - Cousins, Fiona L.
AU - McKinnon, Brett D.
AU - Mortlock, Sally
AU - Fitzgerald, Harriet C.
AU - Zhang, Chenyu
AU - Montgomery, Grant W.
AU - Gargett, Caroline E.
N1 - Funding Information:
This work was supported by the United States Department of Defense, through Congressionally Directed Medical Research Program under Award No. EO1 W81XWH1910364 (to Caroline E. Gargett and Grant W. Montgomery supporting Harriet C. Fitzgerald). Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. Caroline E. Gargett and Grant W. Montgomery are supported by a National Health and Medical Research Council of Australia Investigator Grants (1173882 and 1177194, respectively). This work is also supported by the Victorian Government's Operational Infrastructure Support Program. The authors wish to thank Dr. Thomas Tapmeier for the Tissue Clearing Microscopy icon in Figure 1 . Open access publishing facilitated by Monash University, as part of the Wiley ‐ Monash University agreement via the Council of Australian University Librarians.
Publisher Copyright:
© 2023 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.
PY - 2023/4
Y1 - 2023/4
N2 - Endometriosis is a serious, chronic disorder where endometrial tissue grows outside the uterus, causing severe pelvic pain and infertility. It affects 11% of women. Endometriosis is a multifactorial disorder of unclear etiology, although retrograde menstruation plays a major role. It has a genetic component with over 40 genetic risk factors mapped, although their mechanism of action is still emerging. New evidence suggests a role for retrograde menstruation of endometrial stem/progenitor cells, now that identifying markers of these cells are available. Recent lineage tracing and tissue clearing microscopy and 3D reconstruction has provided new understanding of endometrial glandular structure, particularly the horizontal orientation and interconnection of basalis glands. New sequencing technologies, particularly whole genome DNA sequencing are revealing somatic mutations, including in cancer driver genes, in normal and eutopic endometrium of patients with endometriosis, as well as ectopic endometriotic lesions. Methylome sequencing is offering insight into the regulation of genes and the role of the environmental factors. Single cell RNA sequencing reveals the transcriptome of individual endometrial cells, shedding new light on the diversity and range of cellular subpopulations of the major cell types present in the endometrium and in endometriotic lesions. New endometrial epithelial organoid cultures replicating glandular epithelium are providing tractable models for studying endometriosis. Organoids derived from menstrual fluid offer a non-invasive source of endometrial tissue and a new avenue for testing drugs and developing personalized medicine for treating endometriosis. These new approaches are rapidly advancing our understanding of endometriosis etiology.
AB - Endometriosis is a serious, chronic disorder where endometrial tissue grows outside the uterus, causing severe pelvic pain and infertility. It affects 11% of women. Endometriosis is a multifactorial disorder of unclear etiology, although retrograde menstruation plays a major role. It has a genetic component with over 40 genetic risk factors mapped, although their mechanism of action is still emerging. New evidence suggests a role for retrograde menstruation of endometrial stem/progenitor cells, now that identifying markers of these cells are available. Recent lineage tracing and tissue clearing microscopy and 3D reconstruction has provided new understanding of endometrial glandular structure, particularly the horizontal orientation and interconnection of basalis glands. New sequencing technologies, particularly whole genome DNA sequencing are revealing somatic mutations, including in cancer driver genes, in normal and eutopic endometrium of patients with endometriosis, as well as ectopic endometriotic lesions. Methylome sequencing is offering insight into the regulation of genes and the role of the environmental factors. Single cell RNA sequencing reveals the transcriptome of individual endometrial cells, shedding new light on the diversity and range of cellular subpopulations of the major cell types present in the endometrium and in endometriotic lesions. New endometrial epithelial organoid cultures replicating glandular epithelium are providing tractable models for studying endometriosis. Organoids derived from menstrual fluid offer a non-invasive source of endometrial tissue and a new avenue for testing drugs and developing personalized medicine for treating endometriosis. These new approaches are rapidly advancing our understanding of endometriosis etiology.
KW - endometrial stem/progenitor cells
KW - endometriosis
KW - genetic variants
KW - retrograde menstruation
KW - somatic mutations
UR - http://www.scopus.com/inward/record.url?scp=85147520841&partnerID=8YFLogxK
U2 - 10.1111/jog.15549
DO - 10.1111/jog.15549
M3 - Article
C2 - 36746607
AN - SCOPUS:85147520841
SN - 1341-8076
VL - 49
SP - 1090
EP - 1105
JO - The Journal of Obstetrics and Gynaecology Research
JF - The Journal of Obstetrics and Gynaecology Research
IS - 4
ER -