Annalia Lombardi1, Sofia Makieva2, Sara F Rinaldi2, Felice Arcuri1, Felice Petraglia1, Jane E Norman2. 1. 1 Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. 2. 2 Tommy's Centre for Maternal and Fetal Health, MRC Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Abstract
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.
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 murinelabor (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.
Authors: Daniel J Capone; Gabrielle L Clark; Derek Bivona; Benard O Ogola; Laurephile Desrosiers; Leise R Knoepp; Sarah H Lindsey; Kristin S Miller Journal: J Biomech Date: 2018-11-09 Impact factor: 2.712