Metalloproteinases (MMPs) are involved in menstrual breakdown and endometrial remodeling in primates. We performed immunocytochemical (ICC) studies of the following endometrial MMPs matrilysin (MMP-7), stromelysin-1 (MMP-3) and gelatinase-A (MMP-2), as well as tissue inhibitor of metalloproteinases-1 (TIMP-1). Spayed animals were treated with a sequential estradiol (E2)-progesterone (P) implant regimen for 28 days. Then P was withdrawn (with E2 remaining) to induce menses, and uteri removed 0, 1, 2, 3, 4, 5, 6, 8, 10, 14 and 28 days later. Both E2 and P implants were withdrawn from some animals and these were sampled 3, 5, 10 and 14 days later. Two days after P-withdrawal, all MMPs and TIMP-1 were confined to the upper third of the endometrium where menstrual sloughing occurred. Matrilysin appeared in the upper glands on days 2-5, but then shifted to the lower glands by day 8-14. TIMP-1 at first appeared in the spiral arteries and stroma of the upper zones and then shifted to the glandular epithelium of the lower endometrial zones, in parallel with matrilysin. MMP-3 and MMP-2 first appeared in the stroma of the upper zones and around the spiral arteries and then either disappeared completely (MMP-3) or declined to baseline levels (MMP-2) by day 6. When both E2 and P were withdrawn, patterns and shifts in MMPs and TIMP-1 expression were exactly the same as when E2 was present. Therefore, after P withdrawal, E2 plays no role in increased MMP expression or in the shifts in MMP expression from the upper to lower glands, nor in the expression of MMPs in the spiral arteries. MMP expression and endometrial remodeling after P-withdrawal induced menses apparently involve zone-specific, endogenous regulatory mechanisms that do not depend on E2 action.
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