Oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway
Abstract Pre-eclampsia (PE) is a pregnancy-specific disorder, characterized by hypertension and proteinuria. In PE, trophoblasts mediated inadequate remodeling of uterine spiral arteries seem to interrupt uteroplacental blood flow, one of the hallmarks in the early onset of PE (EO-PE). This, in turn...
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Nature Portfolio
2021-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-97799-y |
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| author | Indrani Mukherjee Ruby Dhar Sunil Singh Jai Bhagwan Sharma Tapas Chandra Nag Asit Ranjan Mridha Parul Jaiswal Subhrajit Biswas Subhradip Karmakar |
| author_facet | Indrani Mukherjee Ruby Dhar Sunil Singh Jai Bhagwan Sharma Tapas Chandra Nag Asit Ranjan Mridha Parul Jaiswal Subhrajit Biswas Subhradip Karmakar |
| author_sort | Indrani Mukherjee |
| collection | DOAJ |
| description | Abstract Pre-eclampsia (PE) is a pregnancy-specific disorder, characterized by hypertension and proteinuria. In PE, trophoblasts mediated inadequate remodeling of uterine spiral arteries seem to interrupt uteroplacental blood flow, one of the hallmarks in the early onset of PE (EO-PE). This, in turn, results in placental ischemia–reperfusion injury during hypoxia and reoxygenation episodes, leading to the generation of reactive oxygen species (ROS) and oxidative stress (OS). But still it is debatable if OS is a cause or consequence of PE. In this present study, we have investigated the effects of OS on PE placentae and trophoblast cell functions using BeWo and HTR8/SVneo cell lines. PE placental tissues showed abnormal ultrastructure, high level of reactive oxygen species (ROS) with altered unfolded protein responses (UPR) in compare with term placental tissues. Similar to PE placentae, during OS induction, the trophoblast cells showed altered invasion and migration properties with significantly variable expression of differentiation and invasion markers, e.g., syncytin and MMPs. The effect was rescued by antioxidant, N-acetyl cysteine, thereby implying a ROS-specific effect and in the trophoblast cells, OS triggers UPR pathway through IRE1α-XBP1 axis. Taken together, these findings highlight the harmful effect of unfolded protein response, which was induced due to OS on trophoblast cells and deformed invasion and differentiation programme and can be extended further to clinical settings to identify clinically approved antioxidants during pregnancy as a therapeutic measure to reduce the onset of PE. |
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| format | Article |
| id | doaj.art-875a04a1c7954d4e9504a5cbd7bff77b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:26:17Z |
| publishDate | 2021-09-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-875a04a1c7954d4e9504a5cbd7bff77b2022-12-21T21:21:06ZengNature PortfolioScientific Reports2045-23222021-09-0111112010.1038/s41598-021-97799-yOxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathwayIndrani Mukherjee0Ruby Dhar1Sunil Singh2Jai Bhagwan Sharma3Tapas Chandra Nag4Asit Ranjan Mridha5Parul Jaiswal6Subhrajit Biswas7Subhradip Karmakar8Department of Biochemistry, All India Institute of Medical SciencesDepartment of Biochemistry, All India Institute of Medical SciencesDepartment of Biochemistry, All India Institute of Medical SciencesDepartment of Obstetrics and Gynaecology, All India Institute of Medical SciencesDepartment of Anatomy, All India Institute of Medical SciencesDepartment of Pathology, All India Institute of Medical SciencesDepartment of Obstetrics and Gynaecology, All India Institute of Medical SciencesResearch Laboratory 101, J3 Block, Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity UniversityDepartment of Biochemistry, All India Institute of Medical SciencesAbstract Pre-eclampsia (PE) is a pregnancy-specific disorder, characterized by hypertension and proteinuria. In PE, trophoblasts mediated inadequate remodeling of uterine spiral arteries seem to interrupt uteroplacental blood flow, one of the hallmarks in the early onset of PE (EO-PE). This, in turn, results in placental ischemia–reperfusion injury during hypoxia and reoxygenation episodes, leading to the generation of reactive oxygen species (ROS) and oxidative stress (OS). But still it is debatable if OS is a cause or consequence of PE. In this present study, we have investigated the effects of OS on PE placentae and trophoblast cell functions using BeWo and HTR8/SVneo cell lines. PE placental tissues showed abnormal ultrastructure, high level of reactive oxygen species (ROS) with altered unfolded protein responses (UPR) in compare with term placental tissues. Similar to PE placentae, during OS induction, the trophoblast cells showed altered invasion and migration properties with significantly variable expression of differentiation and invasion markers, e.g., syncytin and MMPs. The effect was rescued by antioxidant, N-acetyl cysteine, thereby implying a ROS-specific effect and in the trophoblast cells, OS triggers UPR pathway through IRE1α-XBP1 axis. Taken together, these findings highlight the harmful effect of unfolded protein response, which was induced due to OS on trophoblast cells and deformed invasion and differentiation programme and can be extended further to clinical settings to identify clinically approved antioxidants during pregnancy as a therapeutic measure to reduce the onset of PE.https://doi.org/10.1038/s41598-021-97799-y |
| spellingShingle | Indrani Mukherjee Ruby Dhar Sunil Singh Jai Bhagwan Sharma Tapas Chandra Nag Asit Ranjan Mridha Parul Jaiswal Subhrajit Biswas Subhradip Karmakar Oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway Scientific Reports |
| title | Oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway |
| title_full | Oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway |
| title_fullStr | Oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway |
| title_full_unstemmed | Oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway |
| title_short | Oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway |
| title_sort | oxidative stress induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway |
| url | https://doi.org/10.1038/s41598-021-97799-y |
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