title: Premenstrual and menstrual changes in the macaque and human endometrium: relevance to endometriosis.
abstract: 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 NFKB, 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.
authors.affiliation: Oregon Regional Primate Research Center, Oregon Health Sciences University, Beaverton 97006, USA. BrennerR@OHSU.edu
authors.forename: Robert M
authors.initials: RM
authors.lastname: Brenner
authors.forename: Nihar R
authors.initials: NR
authors.lastname: Nayak
authors.forename: Ov D
authors.initials: OD
authors.lastname: Slayden
authors.forename: Hilary O D
authors.initials: HO
authors.lastname: Critchley
authors.forename: Rodney W
authors.initials: RW
authors.lastname: Kelly
mesh_terms: D000818:Animals; D004715:Endometriosis / Q000503:physiopathology; D004717:Endometrium / Q000378:metabolism / Q000502:physiology*; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000378:metabolism; D008251:Macaca; D008598:Menstruation; D017697:Premenopause; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor