Molecular, cellular and tissue mechanisms of endometrial extracellular matrix breakdown leading to abnormal bleeding

Irregular dysfunctional bleeding of human endometrium is associated to and most likely induced by an untimely focal expression and activation of several MMPs, in particular MMP-1, -2, -3 and -9. Moreover, a decreased expression of TIMP-1 contributes to the degradation of the extracellular matrix in the areas where MMPs are expressed. The herogeneously decreased expression of ER alpha and PRA and B is probably involved in a focal loss of repression of the expression of MMPs, which are induced in the stromal cells by interleukin-1 alpha and/or by other as yet unidentified cytokines. Inflammatory cells, in particular neutrophils with their abundant content of proMMP-8 and -9, are recruited at the same sites and release these zymogens, which, once activated, increase the proteolysis of the extracellular matrix. The menstrual-like degradation of the endometrial extracellular matrix and of the basement membranes underlying the vessels and the surface epithelium will induce a bleeding episode, which probably becomes clinically noticeable when (or because) many superficial areas of the endometrium simultaneously undergo the lytic process.(SBIM 3)--UCL, 200