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Tspan5 promotes the EMT process to regulate the syncytialization of trophoblast cells by activating Notch signalling

Published online by Cambridge University Press:  24 July 2023

Hai-Yu Tang Open the ORCID record for Hai-Yu Tang [Opens in a new window] ,
Mei Lin ,
Yong-Qian Liang ,
Jin-Hua Wang ,
Hong-Gan Yi  and
Man Yang
Hai-Yu Tang*
Affiliation:
Department of Reproductive Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou 514000, Guangdong Province, China.
Mei Lin
Affiliation:
Department of Reproductive Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou 514000, Guangdong Province, China.
Yong-Qian Liang
Affiliation:
Department of Reproductive Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou 514000, Guangdong Province, China.
Jin-Hua Wang
Affiliation:
Department of Reproductive Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou 514000, Guangdong Province, China.
Hong-Gan Yi
Affiliation:
Department of Reproductive Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou 514000, Guangdong Province, China.
Man Yang*
Affiliation:
Department of Reproductive Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou 514000, Guangdong Province, China.
*
Corresponding authors: Hai-Yu Tang; Email: 15013204805@163.com Man Yang; Email: 13751992388@163.com
Corresponding authors: Hai-Yu Tang; Email: 15013204805@163.com Man Yang; Email: 13751992388@163.com
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Summary

Placental trophoblastic cells play important roles in placental development and fetal health. However, the mechanism of trophoblastic cell fusion is still not entirely clear. The level of Tspan5 in the embryo culture medium was detected using enzyme-linked immunosorbent assay (ELISA). Fusion of BeWo cells was observed by immunofluorescence. Cell fusion-related factors and EMT-related factors were identified by qRT-PCR and western blotting. Notch protein repressor DAPT was used to verify the role of Tspan5 in BeWo cells. The expression of Tspan5 was significantly increased in embryo culture medium. The fusion of BeWo cells was observed after treatment with forskolin (FSK). Cell fusion-related factors (i.e. β-hCG and syncytin 1/2) and Tspan5 were significantly increased after FSK treatment. In addition, FSK treatment promoted EMT-related protein expression in BeWo cells. Knockdown of Tspan5 inhibited cell fusion and EMT-related protein levels. Notch-1 and Jagged-1 protein levels were significantly upregulated, and the EMT process was activated by overexpression of Tspan5 in FSK-treated BeWo cells. Interestingly, blocking the Notch pathway by the repressor DAPT had the opposite results. These results indicated that Tspan5 could promote the EMT process by activating the Notch pathway, thereby causing cell fusion. These findings contribute to a better understanding of trophoblast cell syncytialization and embryonic development. Tspan5 may be used as a therapeutic target for normal placental development.

Keywords

Cell fusionEMTNotch signalTrophoblast cellsTspan5
Type
Research Article
Information
Zygote , Volume 31 , Issue 5 , October 2023 , pp. 498 - 506
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Copyright
© The Author(s), 2023. Published by Cambridge University Press

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