Matrix Metalloproteinases in Endometrial Breakdown and Repair: Functional Significance in a Mouse Model1

Considerable correlative evidence suggests an important role for matrix metalloproteinases (MMPs) in menstruation, a pro-cess which occurs naturally in very few species. In this study, MMP expression was examined in a mouse model of endome-trial breakdown and repair and the functional importance of MMPs determined. In the model, progesterone support was withdrawn from mice in which endometrial decidualization had been induced; 24 h later, endometrial breakdown was complete, and the entire decidual zone had been shed. Re-epithelialization had occurred by 36 h, and the endometrium had undergone extensive restoration toward a predecidualized state by 48 h. Immunoreactive MMP9 and MMP7 colocalized with leukocyte subsets, particularly neutrophils, whereas MMP13 staining was always extracellular. MMP3 and MMP7 were abundant during re-epithelialization in close proximity to newly reforming epi-thelium. The functional importance of MMPs in these processes was examined using two MMP inhibitors, doxycycline and ba-timistat. Both inhibitors effectively reduced MMP activity, as as-sessed by in situ zymography, but did not have significant effects on endometrial breakdown or repair. This study demonstrates that although MMPs are present in abundance during endome-trial breakdown and repair in this mouse model, they are not the key mediators of these processes. female reproductive tract, decidua, menstrual cycle, progester-one, uterus