RESUMO
The processes of implantation and placentation involve the degradation and remodeling of extracellular matrix, cellular proliferation, apoptosis, and differentiation. Evidence indicates that members of the matrix metalloproteinase (MMP) family play crucial roles in these processes. In the present study, we identified the expression and localization of MMP26/endometase/ matrilysin-2 in human placentae at different stages of gestation using methods of reverse transcriptase-polymerase chain reaction, in situ hybridization, and immunohistochemistry. MMP26 was widely localized to villous cytotrophoblast cells, syncytiotrophoblast cells, and to column trophoblasts during early pregnancy. The mRNA and protein level of MMP26 in chorionic villi was highest at Weeks 6-7, and decreased thereafter, reaching its lowest level at the second trimester. The mRNA level was significantly up-regulated in term placenta, while the immunoreactivity remained undetectable. Notably, intense expression of MMP26 was found in fetal nucleated red cells inside the villous capillaries during gestational Weeks 6-9. Strong expression of MMP26 mRNA was also demonstrated in fetal red cells isolated from the whole blood of fetuses at midpregnancy. The expression patterns of MMP26 in human placenta suggests complicated roles for MMP26 during the processes of placentation and hematopoiesis, perhaps working in concert with other members of the MMP family, such as MMP9.
Assuntos
Eritroblastos/enzimologia , Sangue Fetal/citologia , Hematopoese/fisiologia , Metaloproteinases da Matriz/genética , Trofoblastos/enzimologia , Adulto , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Idade Gestacional , Humanos , Metaloproteinases da Matriz/metabolismo , Metaloproteinases da Matriz Secretadas , Placenta/citologia , Placenta/metabolismo , Gravidez , RNA Mensageiro/análiseRESUMO
The integrin and extracellular matrix protein (ECM)-mediated adhesion and invasion of the receptive maternal uterine endometrium by trophoblasts is a critical event in the complex physiological process of pregnancy. Although the process has been largely characterized in mice, the relevant mechanism in primates remains unclear. We investigated the expression patterns and dynamic alterations of integrin subunits (alpha1, alpha5, alpha6, beta1, and beta4) and their ECM ligands, such as laminin (LN), type IV collagen (Col IV), and fibronectin (FN), at the maternal-fetal interface during Gestational Days 15, 25, 50, and 100 and at full term in 20 pregnant rhesus monkeys. Immunohistochemistry and in situ hybridization revealed that a relatively high expression of integrins occurred in trophoblast cells at Gestational Day 15, with the peak level occurring at Day 25. The expression level decreased from Day 50 to term. Along the invasive pathway, expression levels of integrin alpha1, alpha5, and beta1 subunits were gradually elevated from the proximal to distal column, reaching peak level in the trophoblast shell, but were reduced in those invasive extravillous cytotrophoblast (EVCT) cells in contact with the decidua. Integrin alpha1, alpha5, beta1, and beta4 subunits were also highly expressed in decidual stromal cells and moderately expressed in the maternal epithelium and endothelium. Immunoreactive FN, LN, and Col IV were distributed in EVCT and decidual stromal cells and part of the uterine epithelial and endothelial cells. These data suggest that the correlated expression of integrins and their ECM ligands at the maternal-fetal interface might be involved in regulation of cell proliferation and differentiation and the counterbalanced invasion-accelerating and invasion-restraining processes in trophoblast cells during the early stage of pregnancy.