Circulating matrix metalloproteinase MMP-9 and MMP-2/TIMP-2 complex are associated with spontaneous early pregnancy failure

Nissi Ritva, Talvensaari-Mattila Anne, Kotila Vesa, Niinimäki Maarit, Järvelä Ilkka, Turpeenniemi-Hujanen, Turpeenniemi-Hujanen Taina

Description

Trophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation. This invasion is facilitated by the activity of matrix metalloproteinases, which are regulated by tissue inhibitors of MMPs (TIMPs). Methods This study compares the serum levels of MMP-9, MMP-2/TIMP-2 complex, TIMP-1 and TIMP-2 in 129 patients with ongoing pregnancy (n = 40) or spontaneous early pregnancy failure (n = 89). Results MMP-9 was markedly (p < 0.0001) elevated in missed abortions, as was MMP-2/TIMP-2 complex (p < 0.0005). However, the serum levels of TIMP-1 and TIMP-2 were markedly elevated (p < 0.0001) in ongoing pregnancies. Conclusions Human placentation is mediated by fetal trophoblastic cells that invade the maternal uterine endometrium. Trophoblast invasion requires a precisely regulated secretion of specific proteolytic enzymes able to degrade the endometrial basement membrane and extracellular matrix. The elevated levels of MMP-9 and MMP-2/TIMP-2 complex may play a role in spontaneous termination of pregnancy.

Sujets

• MMP2
• MMP9
• Pregnancy
• Miscarriage
• Placentation

Informations

• Publié par: biomed
• Publié le: 01 janvier 2013
• Nombre de lectures: 23
• Langue: English

Extrait

Nissiet al. Reproductive Biology and Endocrinology2013,11:2 http://www.rbej.com/content/11/1/2

R E S E A R C HOpen Access Circulating matrix metalloproteinase MMP9 and MMP2/TIMP2 complex are associated with spontaneous early pregnancy failure 1* 12 11 Ritva Nissi, Anne TalvensaariMattila , Vesa Kotila , Maarit Niinimäki , Ilkka Järvelä 3 and Taina TurpeenniemiHujanen

Abstract Background:Trophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation. This invasion is facilitated by the activity of matrix metalloproteinases, which are regulated by tissue inhibitors of MMPs (TIMPs). Methods:This study compares the serum levels of MMP9, MMP2/TIMP2 complex, TIMP1 and TIMP2 in 129 patients with ongoing pregnancy (n= 40)or spontaneous early pregnancy failure (n= 89). Results:MMP9 was markedly (p <0.0001) elevated in missed abortions, as was MMP2/TIMP2 complex (p < 0.0005).However, the serum levels of TIMP1 and TIMP2 were markedly elevated (p< 0.0001)in ongoing pregnancies. Conclusions:Human placentation is mediated by fetal trophoblastic cells that invade the maternal uterine endometrium. Trophoblast invasion requires a precisely regulated secretion of specific proteolytic enzymes able to degrade the endometrial basement membrane and extracellular matrix. The elevated levels of MMP9 and MMP2/ TIMP2 complex may play a role in spontaneous termination of pregnancy. Keywords:MMP2, MMP9, TIMP1, TIMP2, Pregnancy, Pregnancy loss, Serum marker, Placentation

Background Matrix metalloproteinases (MMPs) can be produced by numerous cell types. In normal adult tissue they are al most undetectable by immunohistochemistry, but injur ies and pregnancy, for example, elevate their protein deposition. MMPs have the ability to break down sev eral proteins of the extracellular matrix (ECM) and they participate actively in remodeling the ECM by degrad ing important matrix scaffold macromolecules. To gether with their tissue inhibitors (TIMPs) they form a balance to maintain normal early pregnancy and placen tal development. The gelatinases MMP2 and MMP9 are especially involved in successful cytotrophoblast invasion in early pregnancy as they are considered key enzymes in

* Correspondence: [e-mail] 1 Department of Obstetrics and Gynecology, Oulu University Hospital, Kajaanintie 52A, Oulu 90220, Finland Full list of author information is available at the end of the article

degradation of basement membrane, which mainly consists of type IV collagen [1,2]. Tissue inhibitors for MMPs, such as TIMP1 and TIMP2, regulate protease activity. MMP2, MMP9, TIMP1 and TIMP2 have been localized in the placental bed using immunohistochemis try andin situhybridization. Immunoreactivity for MMP2 was detected in both decidual cells and extravil lous trophoblasts (EVT), but MMP9 staining was only observed in areas with abundant EVT [14]. In early ges tation weeks (weeks 6 and 7) the secretion of MMP9 in placental bed is very low, but the secretion increases gradually after week 8, and in week 11 the cells produce a large amount of MMP9 [1]. In contrast, biosynthesis of MMP2 is significantly higher in the early stages of the pregnancy [3]. MMP2 has been suggested to be the key regulator of trophoblast invasion in early pregnancy [4]. MMP2 is localized in the placental bed during early pregnancy and it is dominant over MMP9 on the

© 2013 Nissi et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.