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Cited by 59Endometriosis Research and TreatmentMenstrual Health and DisordersReproductive System and Pregnancy

Premenstrual and Menstrual Changes in the Macaque and Human Endometrium: Relevance to Endometriosis

BRENNER, ROBERT M., NAYAK, NIHAR R., SLAYDEN, OV D., CRITCHLEY, HILARY O. D., KELLY, RODNEY W.·2002·Annals of the New York Academy of Sciences
DOI 10.1111/j.1749-6632.2002.tb02766.x
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Abstract

A bstract: According to current theory, endometriosis is initiated during retrograde menstruation when menstrual fragments flow out of the fimbriated end of the fallopian tubes and become established on the ovarian surface or other sites in the peritoneal cavity. In recent years, new data have accumulated on the properties of menstruating tissue itself, and several laboratories agree that this tissue is rich in matrix metalloproteinases (MMPs) that may facilitate endometriotic implantation. Recently, we found that vascular endothelial growth factor (VEGF) and its receptor VEGFR‐2 (KDR) were dramatically upregulated in the stromal cells of the superficial endometrial zones by progesterone (P) withdrawal during the premenstrual phase. A unique role of VEGF at this stage of the cycle may be to stimulate MMP expression in stromal cells because VEGF, KDR, and MMPs were all coordinately induced in these cells in the superficial zone of the primate endometrium by P withdrawal. The rich content of MMPs and VEGF in the menstrual fragments could facilitate attachment and angiogenesis of menstrual fragments in ectopic sites. In addition, a variety of chemokines, cytokines, and cellular regulators are induced by P withdrawal in the premenstrual human endometrium. These include NFκB, prostaglandins, interleukin‐8 (IL‐8), cyclooxygenase‐2 (COX‐2), and monocyte chemotactic peptide‐1 (MCP‐1), among others. The perivascular expression of several of these factors may facilitate the rapid invasion of leukocytes into the endometrium, especially in the superficial zones. Consequently, menstrual fragments may be rich in IL‐8 and MCP‐1, both of which would add to the angiogenic potential of such fragments in ectopic sites. In sum, menstrual tissue is rich in VEGF, KDR, MMPs, leukocytes, chemokines, cytokines, and prostaglandins, all factors that may facilitate attachment and angiogenesis when menstrual fragments exit from the tubes and implant on pelvic sites. Additional research on these and other factors in premenstrual and menstrual endometrium may deepen our understanding of both the establishment and progression of this debilitating disease.

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Authors
BRENNER, R. M., NAYAK, N. R., SLAYDEN, O. D., CRITCHLEY, H. O. D., & KELLY, R. W.
Affiliations
  • Oregon Health & Science University (US)
  • University of Edinburgh (GB)
Corresponding author
BRENNER, ROBERT M.
ORCID
Venue
Annals of the New York Academy of Sciences
Publisher
Wiley
Published
2002-03
Volume
955
Issue
1
Pages
60-74
ISSN
  • 0077-8923 (ISSN-L)
  • 1749-6632
DOI
10.1111/j.1749-6632.2002.tb02766.x
OpenAlex
W2082889023
Cited by
59
References
45
Citations by year
2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 4 · 2017: 4 · 2015: 2 · 2014: 5 · 2012: 3
FWCI
3.70
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1425 d)
Locations
  • Annals of the New York Academy of Sciences (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Menstrual Health and Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords
endometriosis, menstrual endometrium, matrix metalloproteinases, vascular endothelial growth factor, VEGFR2, progesterone withdrawal, endometrial stromal cells, retrograde menstruation, angiogenesis, endometrial implantation, chemokines, interleukin-8, human endometrium
MeSH terms
Animals, Endometriosis, Endometrium, Female, Humans, Lymphokines, Macaca, Menstruation, Endothelial Growth Factors, Premenopause, Receptors, Growth Factor, Receptor Protein-Tyrosine Kinases, Receptors, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A

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