Syncytiotrophoblast of Placentae from Women with Zika Virus Infection Has Altered Tight Junction Protein Expression and Increased Paracellular Permeability
Jael Miranda,
Dolores Martín-Tapia,
Yolotzin Valdespino-Vázquez,
Lourdes Alarcón,
Aurora Espejel-Nuñez,
Mario Guzmán-Huerta,
José Esteban Muñoz-Medina,
Mineko Shibayama,
Bibiana Chávez-Munguía,
Guadalupe Estrada-Gutiérrez,
Samuel Lievano,
Juan Ernesto Ludert,
Lorenza González-Mariscal
Affiliations
Jael Miranda
Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies (Cinvestav), Mexico City 07360, Mexico
Dolores Martín-Tapia
Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies (Cinvestav), Mexico City 07360, Mexico
Yolotzin Valdespino-Vázquez
Research Division, Instituto Nacional de Perinatología (INPer) Isidro Espinosa de los Reyes, Mexico City 11000, Mexico
Lourdes Alarcón
Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies (Cinvestav), Mexico City 07360, Mexico
Aurora Espejel-Nuñez
Research Division, Instituto Nacional de Perinatología (INPer) Isidro Espinosa de los Reyes, Mexico City 11000, Mexico
Mario Guzmán-Huerta
Research Division, Instituto Nacional de Perinatología (INPer) Isidro Espinosa de los Reyes, Mexico City 11000, Mexico
José Esteban Muñoz-Medina
Laboratorio Central de Epidemiología, Instituto Mexicano del Seguro Social, Ciudad de México 02990, Mexico
Mineko Shibayama
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (Cinvestav), Mexico City 07360, Mexico
Bibiana Chávez-Munguía
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (Cinvestav), Mexico City 07360, Mexico
Guadalupe Estrada-Gutiérrez
Research Division, Instituto Nacional de Perinatología (INPer) Isidro Espinosa de los Reyes, Mexico City 11000, Mexico
Samuel Lievano
Quality division, Obstetrics and Gynecology Hospital No. 4, Mexican Institute of Social Security (IMSS), Mexico City 01090, Mexico
Juan Ernesto Ludert
Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (Cinvestav), Mexico City 07360, Mexico
Lorenza González-Mariscal
Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies (Cinvestav), Mexico City 07360, Mexico
The cytotrophoblast of human placenta transitions into an outer multinucleated syncytiotrophoblast (STB) layer that covers chorionic villi which are in contact with maternal blood in the intervillous space. During pregnancy, the Zika virus (ZIKV) poses a serious prenatal threat. STB cells are resistant to ZIKV infections, yet placental cells within the mesenchyme of chorionic villi are targets of ZIKV infection. We seek to determine whether ZIKV can open the paracellular pathway of STB cells. This route is regulated by tight junctions (TJs) which are present in the uppermost portion of the lateral membranes of STB cells. We analyzed the paracellular permeability and expression of E-cadherin, occludin, JAMs −B and −C, claudins -1, -3, -4, -5 and -7, and ZO-1, and ZO-2 in the STB of placentae from ZIKV-infected and non-infected women. In ZIKV-infected placentae, the pattern of expression of TJ proteins was preserved, but the amount of claudin-4 diminished. Placentae from ZIKV-infected women were permeable to ruthenium red, and had chorionic villi with a higher mean diameter and Hofbauer hyperplasia. Finally, ZIKV added to the basolateral surface of a trophoblast cell line reduced the transepithelial electrical resistance. These results suggest that ZIKV can open the paracellular pathway of STB cells.
