[Role of matrix metalloproteinases in the endometrium in normal and pathologic menstruation]

Menstruation was thought to be the consequence of ischemic necrosis of the endometrium, resulting from vasoconstriction of the spiral arterioles. However, a new paradigm recently emerged when it was shown that human endometrium produces a lot of matrix metalloproteinases (MMPS) at menstruation. These MMPS are active and degrade almost all constituents of the extracellular matrix at neutral pH, allowing for tissue fragmentation and shedding. The tight control of their expression by progesterone and the close relationship in time and space between their expression and the lysis of the mucosa suggest their involvement in triggering menses as well as abnormal bleeding. A proof of their involvement was provided by culturing explants in conditions that mimic ex vivo the menstrual degradation of the endometrium, because specific inhibitors of MMPS prevent lysis of the extracellular matrix. Several cytokines have been shown to focally modulate the inhibition of MMPs expression by progesterone in a paracrine way.