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Serum From Preeclamptic Women Triggers Endoplasmic Reticulum Stress Pathway and Expression of Angiogenic Factors in Trophoblast Cells
Preeclampsia (PE) is a hypertensive disease of pregnancy-associated with placental cell death and endoplasmic reticulum (ER) stress. It is unknown whether systemic factors aggravate placental dysfunction. We investigated whether serum factors in pregnant women with PE activate ER stress and unfolded...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855099/ https://www.ncbi.nlm.nih.gov/pubmed/35185601 http://dx.doi.org/10.3389/fphys.2021.799653 |
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author | Castro, Karla R. Prado, Karen M. Lorenzon, Aline R. Hoshida, Mara S. Alves, Eliane A. Francisco, Rossana P. V. Zugaib, Marcelo Marques, Aldilane L. X. Silva, Elaine C. O. Fonseca, Eduardo J. S. Borbely, Alexandre U. Veras, Mariana M. Bevilacqua, Estela |
author_facet | Castro, Karla R. Prado, Karen M. Lorenzon, Aline R. Hoshida, Mara S. Alves, Eliane A. Francisco, Rossana P. V. Zugaib, Marcelo Marques, Aldilane L. X. Silva, Elaine C. O. Fonseca, Eduardo J. S. Borbely, Alexandre U. Veras, Mariana M. Bevilacqua, Estela |
author_sort | Castro, Karla R. |
collection | PubMed |
description | Preeclampsia (PE) is a hypertensive disease of pregnancy-associated with placental cell death and endoplasmic reticulum (ER) stress. It is unknown whether systemic factors aggravate placental dysfunction. We investigated whether serum factors in pregnant women with PE activate ER stress and unfolded protein responses (UPRs) in placental explants and trophoblast cells lineage. We cultured placental explants from third-trimester term placentas from control non-preeclamptic (NPE) pregnant women with serum from women with PE or controls (NPE). In PE-treated explants, there was a significant increase in gene expression of GADD34, CHOP, and SDF2. At the protein level, GRP78, SDF2, p-eIF2α, and p-eIF2α/eIF2α ratio were also augmented in treated explants. Assays were also performed in HTR8/SV-neo trophoblast cell line to characterize the putative participation of trophoblast cells. In PE serum-treated protein levels of p-eIF2a and the ratio p-elF2 α/elF2α increased after 12 h of treatment, while the gene expression of GADD34, ATF4, and CHOP was greater than control. Increased expression of SDF2 was also detected after 24 h-cultured HTR8/SV-neo cells. PE serum increased sFLT1 gene expression and decreased PlGF gene expression in placental explants. Morphologically, PE serum increased the number of syncytial knots and reduced placental cell metabolism and viability. Analysis of the serum of pregnant women with PE through Raman spectroscopy showed changes in amino acids, carotenoids, lipids, and DNA/RNA, which may be associated with the induction of ER stress found in chorionic villi treated with this serum. In conclusion, this study provides evidence that the serum of pregnant women with PE may impact placental villi changing its morphology, viability, and secreted functional factors while triggers ER stress and an UPR. The differences between PE and control sera include molecules acting as inducing factors in these processes. In summary, the results obtained in our assays suggest that after the development of PE, the serum profile of pregnant women may be an additional factor that feeds a continuous imbalance of placental homeostasis. In addition, this study may expand the possibilities for understanding the pathogenesis of this disorder. |
format | Online Article Text |
id | pubmed-8855099 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88550992022-02-19 Serum From Preeclamptic Women Triggers Endoplasmic Reticulum Stress Pathway and Expression of Angiogenic Factors in Trophoblast Cells Castro, Karla R. Prado, Karen M. Lorenzon, Aline R. Hoshida, Mara S. Alves, Eliane A. Francisco, Rossana P. V. Zugaib, Marcelo Marques, Aldilane L. X. Silva, Elaine C. O. Fonseca, Eduardo J. S. Borbely, Alexandre U. Veras, Mariana M. Bevilacqua, Estela Front Physiol Physiology Preeclampsia (PE) is a hypertensive disease of pregnancy-associated with placental cell death and endoplasmic reticulum (ER) stress. It is unknown whether systemic factors aggravate placental dysfunction. We investigated whether serum factors in pregnant women with PE activate ER stress and unfolded protein responses (UPRs) in placental explants and trophoblast cells lineage. We cultured placental explants from third-trimester term placentas from control non-preeclamptic (NPE) pregnant women with serum from women with PE or controls (NPE). In PE-treated explants, there was a significant increase in gene expression of GADD34, CHOP, and SDF2. At the protein level, GRP78, SDF2, p-eIF2α, and p-eIF2α/eIF2α ratio were also augmented in treated explants. Assays were also performed in HTR8/SV-neo trophoblast cell line to characterize the putative participation of trophoblast cells. In PE serum-treated protein levels of p-eIF2a and the ratio p-elF2 α/elF2α increased after 12 h of treatment, while the gene expression of GADD34, ATF4, and CHOP was greater than control. Increased expression of SDF2 was also detected after 24 h-cultured HTR8/SV-neo cells. PE serum increased sFLT1 gene expression and decreased PlGF gene expression in placental explants. Morphologically, PE serum increased the number of syncytial knots and reduced placental cell metabolism and viability. Analysis of the serum of pregnant women with PE through Raman spectroscopy showed changes in amino acids, carotenoids, lipids, and DNA/RNA, which may be associated with the induction of ER stress found in chorionic villi treated with this serum. In conclusion, this study provides evidence that the serum of pregnant women with PE may impact placental villi changing its morphology, viability, and secreted functional factors while triggers ER stress and an UPR. The differences between PE and control sera include molecules acting as inducing factors in these processes. In summary, the results obtained in our assays suggest that after the development of PE, the serum profile of pregnant women may be an additional factor that feeds a continuous imbalance of placental homeostasis. In addition, this study may expand the possibilities for understanding the pathogenesis of this disorder. Frontiers Media S.A. 2022-02-04 /pmc/articles/PMC8855099/ /pubmed/35185601 http://dx.doi.org/10.3389/fphys.2021.799653 Text en Copyright © 2022 Castro, Prado, Lorenzon, Hoshida, Alves, Francisco, Zugaib, Marques, Silva, Fonseca, Borbely, Veras and Bevilacqua. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Castro, Karla R. Prado, Karen M. Lorenzon, Aline R. Hoshida, Mara S. Alves, Eliane A. Francisco, Rossana P. V. Zugaib, Marcelo Marques, Aldilane L. X. Silva, Elaine C. O. Fonseca, Eduardo J. S. Borbely, Alexandre U. Veras, Mariana M. Bevilacqua, Estela Serum From Preeclamptic Women Triggers Endoplasmic Reticulum Stress Pathway and Expression of Angiogenic Factors in Trophoblast Cells |
title | Serum From Preeclamptic Women Triggers Endoplasmic Reticulum Stress Pathway and Expression of Angiogenic Factors in Trophoblast Cells |
title_full | Serum From Preeclamptic Women Triggers Endoplasmic Reticulum Stress Pathway and Expression of Angiogenic Factors in Trophoblast Cells |
title_fullStr | Serum From Preeclamptic Women Triggers Endoplasmic Reticulum Stress Pathway and Expression of Angiogenic Factors in Trophoblast Cells |
title_full_unstemmed | Serum From Preeclamptic Women Triggers Endoplasmic Reticulum Stress Pathway and Expression of Angiogenic Factors in Trophoblast Cells |
title_short | Serum From Preeclamptic Women Triggers Endoplasmic Reticulum Stress Pathway and Expression of Angiogenic Factors in Trophoblast Cells |
title_sort | serum from preeclamptic women triggers endoplasmic reticulum stress pathway and expression of angiogenic factors in trophoblast cells |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855099/ https://www.ncbi.nlm.nih.gov/pubmed/35185601 http://dx.doi.org/10.3389/fphys.2021.799653 |
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