Premenstrual and Menstrual Changes in the Macaque and Human Endometrium

Brenner RM, Robert M Brenner, Robert Brenner, Nihar R. Nayak, Nayak NR, Ov D. Slayden, Slayden OD, Hilary Critchley, Critchley HO, Hilary O D Critchley, Rodney W Kelly, R.W. Kelly, Kelly Rw
Annals of the New York Academy of Sciences · 2002 · vol. 955(1) , pp. 60–74 · doi:10.1111/j.1749-6632.2002.tb02766.x · PMID:11949966 · W2082889023
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Progesterone withdrawal in the premenstrual endometrium upregulates VEGF, MMPs, chemokines, and cytokines, potentially facilitating the attachment and angiogenesis of menstrual fragments at ectopic sites.

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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.

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Condition tags

endometriosis

MeSH descriptors

Endometrium Menstruation Premenopause Animals Endometriosis Endometriosis Endometrium Endometrium Endothelial Growth Factors Endothelial Growth Factors Female Humans Lymphokines Lymphokines Macaca Receptor Protein-Tyrosine Kinases Receptor Protein-Tyrosine Kinases Receptors, Growth Factor Receptors, Growth Factor Receptors, Vascular Endothelial Growth Factor

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