Female Reproductive Tract

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

Abstract
Considerable correlative evidence suggests an important role for matrix metalloproteinases (MMPs) in menstruation, a process which occurs naturally in very few species. In this study, MMP expression was examined in a mouse model of endometrial breakdown and repair and the functional importance of MMPs determined. In the model progesterone (P) support was withdrawn from mice in which endometrial decidualization had been induced: 24h later, endometrial breakdown was complete, and the entire decidual zone shed. Re-epithelialization had occurred by 36h, and the endometrium had undergone extensive restoration towards a pre-decidualised state by 48h. Immunoreactive MMP9 and -7 co-localized with leukocyte subsets, particularly neutrophils, whilst MMP13 staining was always extracellular. MMP3 and -7 were abundant during re-epithelialization in close proximity to newly reforming epithelium. The functional importance of MMPs in these processes was examined using two MMP inhibitors, doxycycline and batimistat. Both inhibitors effectively reduced MMP activity, assessed 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 endometrial breakdown and repair in this mouse model, they are not the key mediators of these processes.

Key words: Female Reproductive Tract • Decidua • Menstrual cycle • Progesterone • Uterus

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