Coordinate Expression of Matrix Metalloproteinase Family Members in the Uterus of Normal, Matrilysin-Deficient, and Stromelysin-1-Deficient Mice*

Abstract

The expression patterns of matrix metalloproteinase (MMP) family members during the murine estrous cycle and postpartum uterine involution were analyzed, and the consequence of removing specific MMPs during uterine functions was determined using mice deficient in either matrilysin (MAT) or stromelysin-1 (STR-1). In wild-type animals, MAT, STR-1, STR-2, STR-3, and gelatinase A were consistently expressed during the most active phases of the estrous cycle, estrus and proestrus. The messenger RNA for these MMPs as well as collagenase-3 and the tissue inhibitors of metalloproteinases were also expressed during uterine involution, as determined by Northern analysis and in situ hybridization. Notably, MAT, STR-2, and collagenase-3 messenger RNA levels were elevated at early times of involution and rapidly decreased with time, whereas the transcripts for other MMPs remained elevated throughout the involution process. Involution proceeded normally in mice lacking MAT or STR-1; however, the expression of STR-1 and STR-2 was dramatically up-regulated in MAT nullizygous mice, and the expression of MAT and STR-2 was moderately up-regulated in STR-1-deficient animals. We conclude that the concerted action of several MMPs is likely to play an important role in the remodeling of the postpartum uterus, and that mechanisms that compensate for the loss of a specific MMP during this process appear to exist.

RETRACTED: Expression of matrix metalloproteinase-26 (MMP-26) mRNA in mouse uterus during the estrous cycle and early pregnancy

“…MMP-26 expression was restricted to epithelial cells of the endometrium (Park et al, 2002), while a very restricted expression pattern was also observed for MMP-7 with mRNA transcripts detected in the endometrium (Wilson and Matrisian, 1996). Expression of MMP-7 in uterus during the estrous cycle in rodents has been reported being most abundant at estrus and proestrus (Rudolph-Owens et al, 1997;Woessner, 1996). In our study, the expression pattern of MMP-26 in mouse uterus during the estrous cycle was similar to that of MMP-7.…”

Cellular turnover and extracellular matrix remodeling in female reproductive tissues: functions of metalloproteinases and their inhibitors

“…In contrast, transcripts of other MMPs (MMP-2, MMP-13) and TIMPs were not altered in these mice. Similarly, MMP-3 deficiency had no effect on uterine involution but the mice showed a marked increase in the expression of the MMPs listed above, without changes in TIMP expression [101]. This suggests that a number of MMPs are able to compensate the lack of a specific MMP during remodeling events in the uterus.…”

“…During metestrus, the endometrial wet weight and collagen content decrease to 20% of the proestrus level [85]. MMP-7, MMP-3, MMP-9, MMP-10, and MMP-11, normally found in virgin rat uteri [100 -102], were maximally expressed during estrus and proestrus and were lowest during diestrus [101]. The expression of TIMPs was not examined.…”

“…A loss of collagen accounts for most of the reduction in uterine size [163,164]. In mice, TIMP-1, -2 and -3 mRNA levels remain relatively constant throughout uterine involution [101]. In contrast, MMP-7, MMP-10, and MMP-13 are high during early stages of involution, decreasing to undetectable levels by day 4.5 of involution.…”

“…In contrast, MMP-7, MMP-10, and MMP-13 are high during early stages of involution, decreasing to undetectable levels by day 4.5 of involution. In situ hybridization indicated that TIMPs are concentrated in the myometrium with low expression in the connective tissue [101]. To examine the role of MMP-7 and MMP-3 in the involuting uterus, mice deficient in these genes have been examined.…”