
TY  - JOUR
A1  - Novaro, Virginia 
A1  - Colman-Lerner, Alejandro 
A1  - Ortega, Felipe Vadillo 
A1  - Jawerbaum, Alicia 
A1  - Paz, Dante 
A1  - Nostro, Fabiana Lo 
A1  - Pustovrh, Carolina 
A1  - Gimeno, Martha F. 
A1  - González, Elida 
T1  - Regulation of metalloproteinases by nitric oxide in human trophoblast cells in culture
JF  - Reproduction, Fertility and Development
JO  - Reprod. Fertil. Dev.
Y1  - 2001
VL  - 13
IS  - 6
SP  - 411
EP  - 420
KW  - cytotrophoblast cells, embryo implantation, nitric oxide synthase, placentation, syncytiotrophoblast cells.
UR  - https://doi.org/10.1071/RD01036 
N2  - The process of embryo implantation requires extensive remodelling of the endometrial extracellular matrix, a function largely performed by matrix-degrading metalloproteinases (MMPs). In the present study, we used trophoblast cells isolated from human term placentas to study the regulation of MMPs by nitric oxide (NO). Using a combination of zymography, Western blot and indirect immunofluorescence, we showed that MMP-2 and MMP-9 are increased during the conversion from low-motile cytotrophoblast cells to the highly motile and differentiated syncytiotrophoblast multinucleated cells. We also observed an increase in NO production and NO synthase (NOS) expression during this cellular differentiation process. In addition, we demonstrated a positive regulatory role of NO on the activity and protein expression of MMP-2 and MMP-9, because NO donors (NOC-18 and spermine-NONOate) or the NOS substrate (L-arginine) stimulate, whereas NOS inhibitors (NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine) reduce the expression and gelatinolytic activity of MMP-2 and MMP-9 in isolated trophoblast cells. Taken together, these results suggest that, in differentiating trophoblasts, NO regulates the induction of matrix-degrading proteases required for invasion during embryo implantation. 
ER  -

