Exporting Proteins Associated with Senescence Repair via Extracellular Vesicles May Be Associated with Early Pregnancy Loss
Introduction: Dysfunction of placental development is involved in early pregnancy loss. Senescent changes have been seen in missed miscarriage, one type of pregnancy loss. Extracellular vesicles (EVs) have been widely implicated in the pathogenesis of diseases. In this study, we investigated the pro...
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MDPI AG
2022-09-01
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| author | Yi Zhang Yunhui Tang Xinyi Sun Matt Kang Min Zhao Jiayi Wan Qi Chen |
| author_facet | Yi Zhang Yunhui Tang Xinyi Sun Matt Kang Min Zhao Jiayi Wan Qi Chen |
| author_sort | Yi Zhang |
| collection | DOAJ |
| description | Introduction: Dysfunction of placental development is involved in early pregnancy loss. Senescent changes have been seen in missed miscarriage, one type of pregnancy loss. Extracellular vesicles (EVs) have been widely implicated in the pathogenesis of diseases. In this study, we investigated the protein profiles in placental EVs derived from missed miscarriage in comparison with healthy pregnancy. We also investigated whether cargos packed into EVs are involved in the dysfunctional development of the placenta seen in missed miscarriage. Methods: Proteomic analysis of placental EVs derived from healthy and missed-miscarriage placentae was performed. Three senescence-repair-associated proteins, replication protein A-70 (RPA-70), proteasome activator subunit-4 (PMSE-4), and protein activated kinase-2, (PAK-2) were examined in placental EVs and placentae, and in placental explants that had been treated with or without GW4869, by western blotting and immunohistochemistry. Results: The total number of proteins associated with placental EVs was not different between the two groups. However, there were 106 and 151 abundantly expressed proteins associated with placental micro- or nano-EVs from missed miscarriage in comparison with EVs from controls. Of these abundant proteins, 59 and 81 proteins in placental micro- or nano-EVs, respectively, are associated with DNA damage/repair and cell death/survival. We further found higher levels of three senescence-repair-associated proteins (RPA-70, PMSE-4, and PAK-2) associated with placental EVs, but lower levels of these proteins in missed-miscarriage placentae. Regarding inhibition of EV formation or release by GW4869, we found that the expression of these three proteins was higher in GW4869-treated placental explants from missed miscarriage. Discussion: Our data may suggest that “inadvertently” sorting of cargos and exporting proteins associated with senescence-repair by placental EVs may be associated with the dysfunction of placental development seen in missed miscarriage. |
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| publishDate | 2022-09-01 |
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| spelling | doaj.art-1cbce6ff555b4623b04a93950e99a1842023-11-23T15:32:00ZengMDPI AGCells2073-44092022-09-011118277210.3390/cells11182772Exporting Proteins Associated with Senescence Repair via Extracellular Vesicles May Be Associated with Early Pregnancy LossYi Zhang0Yunhui Tang1Xinyi Sun2Matt Kang3Min Zhao4Jiayi Wan5Qi Chen6Department of Obstetrics & Gynaecology, The University of Auckland, Auckland 1141, New ZealandDepartment of Family Planning, The Hospital of Obstetrics & Gynaecology, Fudan University, Shanghai 200082, ChinaDepartment of Obstetrics & Gynaecology, The University of Auckland, Auckland 1141, New ZealandDepartment of Obstetrics & Gynaecology, The University of Auckland, Auckland 1141, New ZealandDepartment of Gynaecological Cancer, Wuxi Maternity and Child Health Hospital Affiliated Nanjing Medical University, Wuxi 214002, ChinaDepartment of Pathology, Wuxi No 2 People’s Hospital, Nanjing Medical University, Wuxi 214002, ChinaDepartment of Obstetrics & Gynaecology, The University of Auckland, Auckland 1141, New ZealandIntroduction: Dysfunction of placental development is involved in early pregnancy loss. Senescent changes have been seen in missed miscarriage, one type of pregnancy loss. Extracellular vesicles (EVs) have been widely implicated in the pathogenesis of diseases. In this study, we investigated the protein profiles in placental EVs derived from missed miscarriage in comparison with healthy pregnancy. We also investigated whether cargos packed into EVs are involved in the dysfunctional development of the placenta seen in missed miscarriage. Methods: Proteomic analysis of placental EVs derived from healthy and missed-miscarriage placentae was performed. Three senescence-repair-associated proteins, replication protein A-70 (RPA-70), proteasome activator subunit-4 (PMSE-4), and protein activated kinase-2, (PAK-2) were examined in placental EVs and placentae, and in placental explants that had been treated with or without GW4869, by western blotting and immunohistochemistry. Results: The total number of proteins associated with placental EVs was not different between the two groups. However, there were 106 and 151 abundantly expressed proteins associated with placental micro- or nano-EVs from missed miscarriage in comparison with EVs from controls. Of these abundant proteins, 59 and 81 proteins in placental micro- or nano-EVs, respectively, are associated with DNA damage/repair and cell death/survival. We further found higher levels of three senescence-repair-associated proteins (RPA-70, PMSE-4, and PAK-2) associated with placental EVs, but lower levels of these proteins in missed-miscarriage placentae. Regarding inhibition of EV formation or release by GW4869, we found that the expression of these three proteins was higher in GW4869-treated placental explants from missed miscarriage. Discussion: Our data may suggest that “inadvertently” sorting of cargos and exporting proteins associated with senescence-repair by placental EVs may be associated with the dysfunction of placental development seen in missed miscarriage.https://www.mdpi.com/2073-4409/11/18/2772placental EVsproteomicssorting of cargoinhibitor of EV formationmissed miscarriagesenescence-repair |
| spellingShingle | Yi Zhang Yunhui Tang Xinyi Sun Matt Kang Min Zhao Jiayi Wan Qi Chen Exporting Proteins Associated with Senescence Repair via Extracellular Vesicles May Be Associated with Early Pregnancy Loss Cells placental EVs proteomics sorting of cargo inhibitor of EV formation missed miscarriage senescence-repair |
| title | Exporting Proteins Associated with Senescence Repair via Extracellular Vesicles May Be Associated with Early Pregnancy Loss |
| title_full | Exporting Proteins Associated with Senescence Repair via Extracellular Vesicles May Be Associated with Early Pregnancy Loss |
| title_fullStr | Exporting Proteins Associated with Senescence Repair via Extracellular Vesicles May Be Associated with Early Pregnancy Loss |
| title_full_unstemmed | Exporting Proteins Associated with Senescence Repair via Extracellular Vesicles May Be Associated with Early Pregnancy Loss |
| title_short | Exporting Proteins Associated with Senescence Repair via Extracellular Vesicles May Be Associated with Early Pregnancy Loss |
| title_sort | exporting proteins associated with senescence repair via extracellular vesicles may be associated with early pregnancy loss |
| topic | placental EVs proteomics sorting of cargo inhibitor of EV formation missed miscarriage senescence-repair |
| url | https://www.mdpi.com/2073-4409/11/18/2772 |
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