{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:15:20Z","timestamp":1788894920229,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T00:00:00Z","timestamp":1720224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FONDECYT","award":["#1160227"],"award-info":[{"award-number":["#1160227"]}]},{"name":"FONDECYT","award":["#1240485"],"award-info":[{"award-number":["#1240485"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Extravillous trophoblasts (EVTs) form stratified columns at the placenta\u2013uterus interface. In the closest part to fetal structures, EVTs have a proliferative phenotype, whereas in the closest part to maternal structures, they present a migratory phenotype. During the placentation process, Connexin 40 (Cx40) participates in both the proliferation and migration of EVTs, which occurs under hypoxia. However, a possible interaction between hypoxia and Cx40 has not yet been established. Methods: We developed two cellular models, one with \u201clow Cx40\u201d (Jeg-3), which reflected the expression of this protein found in migratory EVTs, and one with \u201chigh Cx40\u201d (Jeg-3\/hCx40), which reflected the expression of this protein in proliferative cells. We analyzed the migration and proliferation of these cells under normoxic and hypoxic conditions for 24 h. Jeg-3 cells under hypoxia increased their migratory capacity over their proliferative capacity. However, in Jeg-3\/hCx40, the opposite effect was induced. On the other hand, hypoxia promoted gap junction (GJ) plaque formation between neighboring Jeg-3 cells. Similarly, the activation of a nitro oxide (NO)\/cGMP\/PKG-dependent pathway induced an increase in GJ-plaque formation in Jeg-3 cells. Conclusions: The expression patterns of Cx40 play a crucial role in shaping the responses of EVTs to hypoxia, thereby influencing their migratory or proliferative phenotype. Simultaneously, hypoxia triggers an increase in Cx40 gap junction (GJ) plaque formation through a pathway dependent on NO.<\/jats:p>","DOI":"10.3390\/cells13131150","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T04:52:49Z","timestamp":1720414369000},"page":"1150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cx40 Levels Regulate Hypoxia-Induced Changes in the Migration, Proliferation, and Formation of Gap Junction Plaques in an Extravillous Trophoblast Cell Model"],"prefix":"10.3390","volume":"13","author":[{"given":"Fernanda M.","family":"Rozas-Villanueva","sequence":"first","affiliation":[{"name":"Programa de Comunicaci\u00f3n Celular en C\u00e1ncer, Facultad de Medicina Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7550000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0686-3432","authenticated-orcid":false,"given":"Viviana P.","family":"Orellana","sequence":"additional","affiliation":[{"name":"Programa de Comunicaci\u00f3n Celular en C\u00e1ncer, Facultad de Medicina Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7550000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Alarc\u00f3n","sequence":"additional","affiliation":[{"name":"Programa de Comunicaci\u00f3n Celular en C\u00e1ncer, Facultad de Medicina Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7550000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Maripillan","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinario de Neurociencias de Valpara\u00edso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valpara\u00edso, Valpara\u00edso 2360102, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7842-8400","authenticated-orcid":false,"given":"Agustin D.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinario de Neurociencias de Valpara\u00edso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valpara\u00edso, Valpara\u00edso 2360102, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5938-5940","authenticated-orcid":false,"given":"Ivan E.","family":"Alfaro","sequence":"additional","affiliation":[{"name":"Programa de Comunicaci\u00f3n Celular en C\u00e1ncer, Facultad de Medicina Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7550000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2562-6686","authenticated-orcid":false,"given":"Mauricio A.","family":"Retamal","sequence":"additional","affiliation":[{"name":"Programa de Comunicaci\u00f3n Celular en C\u00e1ncer, Facultad de Medicina Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7550000, Chile"},{"name":"Center for Membrane Protein Research, Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,6]]},"reference":[{"key":"ref_1","first-page":"190","article-title":"Human placental trophoblast invasion and differentiation: A particular focus on Wnt signaling","volume":"4","author":"Pollheimer","year":"2013","journal-title":"Front. 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