Senescent Changes and Endoplasmic Reticulum Stress May Be Involved in the Pathogenesis of Missed Miscarriage
BackgroundSenescence is involved in many complications of pregnancy. However, whether senescent changes are also associated with missed miscarriage has not been fully investigated.MethodsThe levels of p16, p21, and γH2AX, markers of senescence, were measured in placentas collected from women with mi...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.656549/full |
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| author | Yunhui Tang Xinyan Zhang Yi Zhang Hua Feng Jing Gao Haiyan Liu Fang Guo Qi Chen |
| author_facet | Yunhui Tang Xinyan Zhang Yi Zhang Hua Feng Jing Gao Haiyan Liu Fang Guo Qi Chen |
| author_sort | Yunhui Tang |
| collection | DOAJ |
| description | BackgroundSenescence is involved in many complications of pregnancy. However, whether senescent changes are also associated with missed miscarriage has not been fully investigated.MethodsThe levels of p16, p21, and γH2AX, markers of senescence, were measured in placentas collected from women with missed miscarriage by immunohistochemistry and Western blotting. Levels of misfolded proteins in missed miscarriage placentas or normal first-trimester placenta that had been treated with H2O2 (100 μM) or extracellular vesicles (EVs) collected from missed miscarriage placental explant culture were measured by fluorescent compound, thioflavin-T. The production of reactive oxygen species (ROS) by missed miscarriage placentas was measured by CellROX® Deep Red.ResultsIncreased levels of p16, p21, and γH2AX were presented in missed miscarriage placentas compared to controls. Increased levels of misfolded proteins were shown in missed miscarriage placentas, but not in EVs that were collected from missed miscarriage placentas. The ROS production was significantly increased in missed miscarriage placental explant cultures. Increased levels of misfolded proteins were seen in the normal first-trimester placenta that had been treated with H2O2 compared to untreated.ConclusionOur data demonstrate that there are increases in senescence and endoplasmic reticulum stress and ROS production in missed miscarriage placenta. Oxidative stress and an accumulation of misfolded proteins in missed miscarriage placentas may contribute to the changes of senescence and endoplasmic reticulum stress seen in missed miscarriage placentas. |
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| language | English |
| last_indexed | 2024-12-16T13:01:31Z |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-d8a0a8f358ef43cf82bddb051c8436492022-12-21T22:30:50ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-06-01910.3389/fcell.2021.656549656549Senescent Changes and Endoplasmic Reticulum Stress May Be Involved in the Pathogenesis of Missed MiscarriageYunhui Tang0Xinyan Zhang1Yi Zhang2Hua Feng3Jing Gao4Haiyan Liu5Fang Guo6Qi Chen7Department of Family Planning, The Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, ChinaThe Institution of Obstetrics and Gynaecology, The Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, ChinaDepartment of Obstetrics and Gynaecology, The University of Auckland, Auckland, New ZealandDepartment of Cervical Disease, The Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, ChinaDepartment of Medical Laboratory, The Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, ChinaDepartment of Obstetrics, The Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, ChinaDepartment of Obstetrics, The Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, ChinaDepartment of Obstetrics and Gynaecology, The University of Auckland, Auckland, New ZealandBackgroundSenescence is involved in many complications of pregnancy. However, whether senescent changes are also associated with missed miscarriage has not been fully investigated.MethodsThe levels of p16, p21, and γH2AX, markers of senescence, were measured in placentas collected from women with missed miscarriage by immunohistochemistry and Western blotting. Levels of misfolded proteins in missed miscarriage placentas or normal first-trimester placenta that had been treated with H2O2 (100 μM) or extracellular vesicles (EVs) collected from missed miscarriage placental explant culture were measured by fluorescent compound, thioflavin-T. The production of reactive oxygen species (ROS) by missed miscarriage placentas was measured by CellROX® Deep Red.ResultsIncreased levels of p16, p21, and γH2AX were presented in missed miscarriage placentas compared to controls. Increased levels of misfolded proteins were shown in missed miscarriage placentas, but not in EVs that were collected from missed miscarriage placentas. The ROS production was significantly increased in missed miscarriage placental explant cultures. Increased levels of misfolded proteins were seen in the normal first-trimester placenta that had been treated with H2O2 compared to untreated.ConclusionOur data demonstrate that there are increases in senescence and endoplasmic reticulum stress and ROS production in missed miscarriage placenta. Oxidative stress and an accumulation of misfolded proteins in missed miscarriage placentas may contribute to the changes of senescence and endoplasmic reticulum stress seen in missed miscarriage placentas.https://www.frontiersin.org/articles/10.3389/fcell.2021.656549/fullplacentamiscarriagesenescenceendoplasmic reticulum stressextracellular vesiclesmisfolded proteins |
| spellingShingle | Yunhui Tang Xinyan Zhang Yi Zhang Hua Feng Jing Gao Haiyan Liu Fang Guo Qi Chen Senescent Changes and Endoplasmic Reticulum Stress May Be Involved in the Pathogenesis of Missed Miscarriage Frontiers in Cell and Developmental Biology placenta miscarriage senescence endoplasmic reticulum stress extracellular vesicles misfolded proteins |
| title | Senescent Changes and Endoplasmic Reticulum Stress May Be Involved in the Pathogenesis of Missed Miscarriage |
| title_full | Senescent Changes and Endoplasmic Reticulum Stress May Be Involved in the Pathogenesis of Missed Miscarriage |
| title_fullStr | Senescent Changes and Endoplasmic Reticulum Stress May Be Involved in the Pathogenesis of Missed Miscarriage |
| title_full_unstemmed | Senescent Changes and Endoplasmic Reticulum Stress May Be Involved in the Pathogenesis of Missed Miscarriage |
| title_short | Senescent Changes and Endoplasmic Reticulum Stress May Be Involved in the Pathogenesis of Missed Miscarriage |
| title_sort | senescent changes and endoplasmic reticulum stress may be involved in the pathogenesis of missed miscarriage |
| topic | placenta miscarriage senescence endoplasmic reticulum stress extracellular vesicles misfolded proteins |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.656549/full |
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