Expression of Matrix Metalloproteinases in the Mouse Uterus and Human Myometrium During Pregnancy, Labor, and Preterm Labor.

BACKGROUND

Uterine extracellular matrix (ECM) remodeling occurs throughout pregnancy and at parturition. Imbalanced availability of key mediators in ECM degradation, namely, matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), is implicated in the pathogenesis of preterm labor (PTL).

OBJECTIVES

Examine the expression of MMPs and their inhibitors TIMPs in (a) the mouse uterus throughout normal gestation, at labor, and during inflammation-induced PTL and (b) the human term and preterm myometrium.

METHODS

The expression of Mmp-2/9/3/10 and Timp-1/2 was determined in the uterus of C57BL/6 mice (n = 6/group) during pregnancy (on days (d) 5, 8, 12, 15, 17, and 18), at normal labor, and during lipopolysaccharide-induced PTL (n = 6/group). The expression of MMP-10 and TIMP-1 was determined in human term and preterm myometrium before the onset of labor (TNL, n = 7; PTNL, n = 7) and during active labor (TL, n = 8; PTL, n = 8). Gene expression and tissue localization were assessed by quantitative polymerase chain reaction and immunohistochemistry, respectively.

RESULTS

Mmp-10 was higher during murine labor (53-fold vs early pregnancy) in contrast to Mmp-2/3/9 and Timp-1, the expression of which reached a nadir at labor ( P < .001 vs d5 [ Mmp-2/ 9] or P < .05 vs d8 [ Mmp-3 and Timp-1]). The Mmp-3/10 and Timp-1 were localized to the uterine epithelium and stroma/myometrium. In the human myometrium, TIMP-1 messenger RNA was higher and MMP-10 was lower in TL versus TNL ( P < .05), PTL ( P < .001), and PTNL ( P < .001). MMP-10 and TIMP-1 were localized to the myometrial smooth muscle cells, interstitial fibroblasts, and inflammatory cells.

CONCLUSIONS

These data implicate MMP-3, TIMP-1, and MMP-10 in the uterine ECM remodeling during physiological and pathological parturition.