@misc{10481/108933,
year = {2025},
month = {12},
url = {https://hdl.handle.net/10481/108933},
abstract = {Trypanosoma cruzi, the causative agent of Chagas disease, can cross the placental barrier and
be transmitted congenitally, yet the mechanisms underlying this process remain incompletely understood. Recent evidence suggests that T. cruzi-derived extracellular vesicles
(TcEVs) may facilitate placental invasion by modulating host–pathogen interactions. In
this study, we examined the effects of TcEVs on human placental explants (HPEs), focusing
on their capacity to disrupt tissue architecture and modulate matrix metalloproteinases
MMP-2 and MMP-9, enzymes critical for extracellular matrix remodeling. Term placental
chorionic villi were cultured ex vivo and exposed to TcEVs, heat-inactivated TcEVs, infective
trypomastigotes, or combinations thereof. TcEVs induced ultrastructural damage, including trophoblast detachment and basal lamina disorganization, which were exacerbated
by co-incubation with parasites. Immunohistochemistry and Western blotting revealed
significant upregulation of MMP-2 and MMP-9, while gelatin zymography confirmed
increased enzymatic activity. Our findings demonstrate that TcEVs independently and synergistically with T. cruzi compromise placental integrity by enhancing MMP expression and
activity, thereby priming the placental microenvironment for parasite invasion. Targeting
TcEVs signaling or MMP activation may represent a novel strategy to prevent congenital
transmission of T. cruzi.},
organization = {National Fund for Scientific and Technological Development (FONDECYT; grant numbers 1220105; 11220310; ANID 21201823)},
publisher = {MDPI},
keywords = {Trypanosoma cruzi},
keywords = {Congenital transmission},
keywords = {Extracellular vesicles},
title = {Placental Barrier Breakdown Induced by Trypanosoma cruzi-Derived Exovesicles: A Role for MMP-2 and MMP-9 in Congenital Chagas Disease},
doi = {10.3390/ijms262412131},
author = {Fernández-Moya, Alejandro and Liempi, Ana and Müller, Marioly and Arregui, Rocío and Osuna Ortega, Antonio and Cornet Gómez, Alberto and Castillo, Christian and Kemmerling, Ulrike},
}