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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Autores principales:	Indrani Mukherjee, Ruby Dhar, Sunil Singh, Jai Bhagwan Sharma, Tapas Chandra Nag, Asit Ranjan Mridha, Parul Jaiswal, Subhrajit Biswas, Subhradip Karmakar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/875a04a1c7954d4e9504a5cbd7bff77b
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spelling	oai:doaj.org-article:875a04a1c7954d4e9504a5cbd7bff77b2021-12-02T18:02:06ZOxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway10.1038/s41598-021-97799-y2045-2322https://doaj.org/article/875a04a1c7954d4e9504a5cbd7bff77b2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97799-yhttps://doaj.org/toc/2045-2322Abstract 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.Indrani MukherjeeRuby DharSunil SinghJai Bhagwan SharmaTapas Chandra NagAsit Ranjan MridhaParul JaiswalSubhrajit BiswasSubhradip KarmakarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/875a04a1c7954d4e9504a5cbd7bff77b
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Oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway

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