Cellular Functions of High-Temperature Requirement Factor A4 in Placenta

Chang Zhu Pei, Bum Chae Choi, Jun Hyeok Park, Hyo Young Park, Jinyoung Paek, Kyung Ju Lee, Bo Seong Yun, Young Ju Kim, Kwang Hyun Baek

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


The expression of High-temperature requirement factor A4 (HtrA4) mRNA is significantly lower in the chorionic villi of patients with recurrent pregnancy loss (RPL) than in the control group. We conducted an investigation into the cellular functions of HtrA4 using the CRISPR/Cas9 system and shRNA-HtrA4 to create knockout BeWo cells and HtrA4 knockdown JEG3 cells. Our results indicated that the knockout BeWo cells exhibited reduced capacity for invasion and fusion, but increased levels of proliferation and migration, with a significantly shortened cell cycle compared to wild-type cells. Wild-type BeWo cells highly expressed cell invasion- and fusion-related factors, while knockout BeWo cells highly expressed migration-, proliferation-, and cell cycle-related factors. The shRNA-HtrA4 JEG3 cells showed a decreased capacity for invasion, but an increased capacity for migration, accompanied by a decrease in the expression of cell invasion-related factors and an increase in migration-related factors. Moreover, our ELISA results revealed that the serum HtrA4 level was lower in patients with RPL than in the controls. These findings suggest that HtrA4 depletion may be associated with placental dysfunction.

Original languageEnglish
Article number1459
Issue number11
StatePublished - Jun 2023

Bibliographical note

Funding Information:
This work was supported by the Ministry of Health & Welfare of the Republic of Korea (HI18C0378) and the Basic Science Program Research Program through the National Research Foundation of Republic of Korea funded by the Ministry of Education (grant No. 2019R1A6A1A03032888) awarded to K.H.B.

Publisher Copyright:
© 2023 by the authors.


  • CRISPR/Cas9
  • HtrA4
  • biomarker
  • cellular functions
  • recurrent abortion


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