Exporting Proteins Associated with Senescence Repair via Extracellular Vesicles May Be Associated with Early Pregnancy Loss

Yi Zhang; Yunhui Tang; Xinyi Sun; Matt Kang; Min Zhao; Jiayi Wan; Qi Chen

doi:10.3390/cells11182772

Cells (Sep 2022)

Exporting Proteins Associated with Senescence Repair via Extracellular Vesicles May Be Associated with Early Pregnancy Loss

Yi Zhang,
Yunhui Tang,
Xinyi Sun,
Matt Kang,
Min Zhao,
Jiayi Wan,
Qi Chen

Affiliations

Yi Zhang: Department of Obstetrics & Gynaecology, The University of Auckland, Auckland 1141, New Zealand
Yunhui Tang: Department of Family Planning, The Hospital of Obstetrics & Gynaecology, Fudan University, Shanghai 200082, China
Xinyi Sun: Department of Obstetrics & Gynaecology, The University of Auckland, Auckland 1141, New Zealand
Matt Kang: Department of Obstetrics & Gynaecology, The University of Auckland, Auckland 1141, New Zealand
Min Zhao: Department of Gynaecological Cancer, Wuxi Maternity and Child Health Hospital Affiliated Nanjing Medical University, Wuxi 214002, China
Jiayi Wan: Department of Pathology, Wuxi No 2 People’s Hospital, Nanjing Medical University, Wuxi 214002, China
Qi Chen: Department of Obstetrics & Gynaecology, The University of Auckland, Auckland 1141, New Zealand

DOI: https://doi.org/10.3390/cells11182772
Journal volume & issue: Vol. 11, no. 18
p. 2772

Abstract

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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.

Published in Cells

ISSN: 2073-4409 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General): Cytology
Website: https://www.mdpi.com/journal/cells

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