The matrix metalloproteinases (MMPS) in the decidua and fetal membranes

Abstract

The role of the matrix metalloproteinases (MMPs) in the decidua, fetal membranes and amniotic fluid (AF) has been receiving more and more attention. The MMPs are not only important intermediaries in pathological processes leading to preterm labor but it seems that they also play a crucial role in the activation of labor at term. During normal gestation MMP-1, -2, -3, -7 and -9 are found in the amniotic fluid and fetal membranes. MMP-2 and MMP-3 are expressed constitutively while MMP-9 is barely detectable until labor. At labor, while MMP-9 is the major MMP responsible for gelatinolytic activity in the membranes, MMP-2 is dominant in the decidua. MMP-7 (AF) increases with gestation but does not appear to play a major role in labor. The expression of MMPs is attenuated through the expression of relaxins, integrins and extracellular matrix metalloproteinase inducer (EMMPRIN). Spontaneous preterm delivery (PTD) may be a product of preterm labor (PTL), preterm premature rupture of membranes (P-PROM) or placental abruption. Each of these processes may have differing pathways but the presence of an intrinsic inflammatory response with or without infection seems to involve all etiologies. The inflammatory response is mediated with cytokines such as interleukins -1, -6 and -8 and tumor necrosis factor alpha. MMP-3, MMP-7 and MMP-8 appear to be important in these processes. MMP-9, which is the major MMP involved in normal labor, plays an important role in pathological labor as well. Finally, apoptosis seems to play a role in pathological labor, particularly deliveries involving P-PROM. African-American are at greater risk of PTD than white or Hispanic Americans. Environmental differences may not suffice to explain this phenomenon. Genetic polymorphisms of the MMP genes may help explain the greater risk among this population. Finally, manipulating MMPs may have a role in the prevention of PTD. Agents suggested include indomethacin, N-acetylcysteine, progesterone and specific inhibitors of phosphodiesterase 4.

Protein Microarrays and Midtrimester Amniotic Fluids: A Novel Approach for the Diagnosis of Early Intrauterine Inflammation Related to Preterm Delivery

“…Moreover, as far as MMP, their role in preterm delivery is controversial: some Authors describe a comparable involvement of MMP both in PTD and in TD (35), while others describe the occurrence of MMP-9 in midpregnancy AF of PTD, suggesting a role ofthis protease in the preterm delivery (11). This last result, apparently not in line with our findings, showing no differences between PTD and TD, may be interpreted assuming that MMP-2 and MMP-9 are not revealed by our study because they are produced at later times, compared to the other intrauterine inflammation markers described above.…”

Reference ranges of matrix metalloproteinase-1, -2, -9 and tissue inhibitor of matrix metalloproteinases-1 concentrations in amniotic fluid in physiological pregnancy

“…Принимая во внимание данные литературы об изменениях в системе ММП в течение родов [3], с целью установления допустимых диапазонов мы исследовали в амниотической жидкости ключевые параметры этой протеолитической системы: концентрации ММП-1, ММП-2, ММП-9 и ТИМП-1 (табл. 2).…”

“…Срочные роды характеризуются постепенным размягчением и расширением шейки матки, сокращениями матки и разрывом оболочек плода [3]. Матриксные металлопротеиназы (ММП) и физиологические регуляторы активности этих ферментов -тканевые ингибиторы матриксных металлопротеиназ (ТИМП) -играют критическую роль в начале родов и разрушении оболочек плода [4].…”

“…Матриксные металлопротеиназы (ММП) и физиологические регуляторы активности этих ферментов -тканевые ингибиторы матриксных металлопротеиназ (ТИМП) -играют критическую роль в начале родов и разрушении оболочек плода [4]. До начала сокращений матки децидуальная оболочка является главным продуцентом ММП-2, ММП-9 и ТИМП-1 [3]. Сразу после начала сокращений миометрия продукция MMП-2 и ММП-9 существенно повышается [5].…”

Regulation of Matrix Metalloproteinases-2 and -9 Gene Expression in Cultured Human Fetal Membrane Cells by Influenza Virus Infection

“…[19][20][21] Particularly, it has been postulated that pro-inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, may have a pivotal role in the etiology of the bacterial infection-associated preterm PROM. This hypothesis is based on the fact that these cytokines have been shown to be able to activate pro-apoptotic proteases (i.e., caspases) and MMP-9 production in isolated fetal membrane tissues, thereby leading to a physical weakening of the tissues.…”