The Autocrine Role of Placental Extracellular Vesicles from Missed Miscarriage in Causing Senescence: Possible Pathogenesis of Missed Miscarriage

Yi Zhang; Yunhui Tang; Yang Liu; Jiayi Wang; Ye Shen; Xinyi Sun; Matthew Kang; Min Zhao; Qi Chen

doi:10.3390/cells11233873

Cells (Dec 2022)

The Autocrine Role of Placental Extracellular Vesicles from Missed Miscarriage in Causing Senescence: Possible Pathogenesis of Missed Miscarriage

Yi Zhang,
Yunhui Tang,
Yang Liu,
Jiayi Wang,
Ye Shen,
Xinyi Sun,
Matthew Kang,
Min Zhao,
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
Yang Liu: Department of Obstetrics & Gynaecology, The University of Auckland, Auckland 1141, New Zealand
Jiayi Wang: Department of Pathology, Wuxi No. 2 People’s Hospital, Nanjing Medical University, Wuxi 214002, China
Ye Shen: Department of Family Planning, Wuxi Maternity and Child Health Hospital Affiliated Nanjing Medical University, Wuxi 214002, China
Xinyi Sun: Department of Obstetrics & Gynaecology, The University of Auckland, Auckland 1141, New Zealand
Matthew 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
Qi Chen: Department of Obstetrics & Gynaecology, The University of Auckland, Auckland 1141, New Zealand

DOI: https://doi.org/10.3390/cells11233873
Journal volume & issue: Vol. 11, no. 23
p. 3873

Abstract

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Placental dysfunction, including senescent changes, is associated with the pathogenesis of missed miscarriage, although the underlying mechanism is unclear. Increasing evidence indicates that placenta-specific miRNAs are packaged in extracellular vesicles (EVs) from placental syncytiotrophoblasts and are released into the maternal circulation. Aberrant cargos including miRNAs in placental EVs have been reported to be associated with the pathogenesis of complicated pregnancies. In this study, we compared the miRNA profiles in EVs derived from missed miscarriage and healthy placentae and investigated possible biological pathways which may be involved in senescence, one cause of missed miscarriage. The total concentration of RNA in placental EVs was not different between the two groups. However, there were 54 and 94 differentially expressed miRNAs in placental large and small EVs from missed miscarriage compared to EVs from healthy controls. The aberrantly expressed miRNAs seen in placental EVs were also observed in missed miscarriage placentae. Gene enrichment analysis showed that some of those differentially expressed miRNAs are involved in cellular senescence, endocytosis, cell cycle and endocrine resistance. Furthermore, transfection of trophoblasts by a single senescence-associated miRNA that was differentially expressed in placental EVs derived from missed miscarriage did not cause trophoblast dysfunction. In contrast, EVs derived from missed miscarriage placenta induced senescent changes in the healthy placenta. Our data suggested that a complex of placental EVs, rather than a few differentially expressed miRNAs in placental EVs derived from missed miscarriage placentae could contribute in an autocrine manner to placental senescence, one of the causes of 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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