Endometriosis impairs bone marrow-derived stem cell recruitment to the uterus whereas bazedoxifene treatment leads to endometriosis regression and improved uterine stem cell engraftment
Open accessAbstract
Endometriosis is a disease defined by the ectopic growth of uterine endometrium. Stem cells contribute to the generation of endometriosis as well as to repair and regeneration of normal endometrium. Here we demonstrate that the selective estrogen receptor modulator bazedoxifene (BZA), administered with conjugated estrogens (CEs), leads to regression of endometriosis lesions as well as reduction in stem cell recruitment to the lesions. Female mice underwent transplantation of male bone marrow. Endometrium was transplanted in the peritoneal cavity of half to create experimental endometriosis. Mice with or without experimental endometriosis were randomized to BZA/CE or vehicle treatment. Endometriosis lesions, bone marrow-derived mesenchymal stem cell engraftment of the lesions, and eutopic endometrium as well as ovarian stimulation were assessed. BZA treatment significantly reduced lesion size, gland number, and expression of proliferation marker proliferating cell nuclear antigen. Ovarian weight was not affected. Stem cells were recruited to the endometriosis lesions, and this recruitment was dramatically reduced by BZA/CE treatment. Stem cell engraftment was reduced in the uterus of animals with endometriosis; however the number of stem cells engrafting the uterus was completely restored by treatment with BZA/CE. Competition between endometriosis and the eutopic endometrium for a limited supply of stem cells and depletion of normal stem cells flux to the uterus is a novel mechanism by which endometriosis interferes with endometrial function and fertility. BZA/CE not only treats lesions of endometriosis, it also dramatically reduces stem cell recruitment to the lesions and restores stem cell engraftment of the uterine endometrium.
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Some mesenchymal/mesothelial cells of the peritoneal cavity, of mesothelial repair after surgery, and in endometrium and endometriosis are directly derived from bone marrow.
“Some of these mesenchymal/ mesothelial cells of the peritoneal cavity (48), of the mesothelial repair after surgery (126) and in endometrium and endometriosis (127-131) are directly derived from bone marrow.”
From Pathogenesis of deep endometriosis (2017) · cites this paper as [130]
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Self-citation
- Authors
- Sakr, S., Naqvi, H., Komm, B., & Taylor, H. S.
- Affiliations
- Yale University (US)
- Pfizer (United States) (US)
- Corresponding author
- Taylor, Hugh S.
- ORCID
- Taylor, Hugh S.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2014-04-01
- Volume
- 155
- Issue
- 4
- Pages
- 1489-1497
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC3959601
- OpenAlex
- W2056529697
- Cited by
- 91
- References
- 74
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 2 · 2023: 6 · 2022: 8 · 2021: 9 · 2020: 7 · 2019: 9 · 2018: 12 · 2017: 11 · 2016: 6 · 2015: 13 · 2014: 2
- FWCI
- 12.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD076422, HD076422)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- endometriosis, bazedoxifene, selective estrogen receptor modulators, bone marrow-derived stem cells, stem cell recruitment, conjugated estrogens, endometrial regeneration, fertility, eutopic endometrium
- MeSH terms
- Animals, Bone Marrow, Bone Marrow Cells, Cell Movement, Endometriosis, Endometrium, Female, Indoles, Male, Mice, Inbred C57BL, Stem Cells, Uterus, Bone Marrow Transplantation, Selective Estrogen Receptor Modulators, Cell Proliferation, Mice
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