{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T05:34:30Z","timestamp":1766122470643,"version":"3.48.0"},"reference-count":75,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"National Fund for Scientific and Technological Development","doi-asserted-by":"crossref","award":["1220105"],"award-info":[{"award-number":["1220105"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002850","name":"National Fund for Scientific and Technological Development","doi-asserted-by":"crossref","award":["11220310"],"award-info":[{"award-number":["11220310"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002850","name":"National Fund for Scientific and Technological Development","doi-asserted-by":"crossref","award":["21201823"],"award-info":[{"award-number":["21201823"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013pathogen 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.<\/jats:p>","DOI":"10.3390\/ijms262412131","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T10:41:23Z","timestamp":1765968083000},"page":"12131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Placental Barrier Breakdown Induced by Trypanosoma cruzi-Derived Exovesicles: A Role for MMP-2 and MMP-9 in Congenital Chagas Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6039-8239","authenticated-orcid":false,"given":"Alejandro","family":"Fern\u00e1ndez-Moya","sequence":"first","affiliation":[{"name":"N\u00facleo Interdisciplinario de Biolog\u00eda y Gen\u00e9tica, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380000, Chile"},{"name":"Instituto de Ciencias Naturales, Facultad de Medicina Veterinaria y Agronom\u00eda, Universidad de Las Am\u00e9ricas, Santiago 9250000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3200-9811","authenticated-orcid":false,"given":"Ana","family":"Liempi","sequence":"additional","affiliation":[{"name":"N\u00facleo Interdisciplinario de Biolog\u00eda y Gen\u00e9tica, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marioly","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Departamento de Tecnolog\u00eda M\u00e9dica, Facultad de Medicina, Universidad de Chile, Santiago 8380000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"Arregui","sequence":"additional","affiliation":[{"name":"N\u00facleo Interdisciplinario de Biolog\u00eda y Gen\u00e9tica, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3818-1471","authenticated-orcid":false,"given":"Antonio","family":"Osuna","sequence":"additional","affiliation":[{"name":"Departamento de Parasitolog\u00eda, Instituto de Biotecnolog\u00eda, Universidad de Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9378-8594","authenticated-orcid":false,"given":"Alberto","family":"Cornet-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Departamento de Parasitolog\u00eda, Instituto de Biotecnolog\u00eda, Universidad de Granada, 18071 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8710-6745","authenticated-orcid":false,"given":"Christian","family":"Castillo","sequence":"additional","affiliation":[{"name":"N\u00facleo Interdisciplinario de Biolog\u00eda y Gen\u00e9tica, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0201-1665","authenticated-orcid":false,"given":"Ulrike","family":"Kemmerling","sequence":"additional","affiliation":[{"name":"N\u00facleo Interdisciplinario de Biolog\u00eda y Gen\u00e9tica, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"ref_1","unstructured":"Castillo, C., Liempi, A., Fern\u00e0ndez-Moya, A., Guerrero-Mu\u00f1oz, J., Araneda, S., C\u00e1ceres, G., Alfaro, S., Gallardo, C.H., Maya, J.D., and M\u00fcller, M. 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