University of Oulu

Tissarinen, P., Tiensuu, H., Haapalainen, A.M. et al. Elevated human placental heat shock protein 5 is associated with spontaneous preterm birth. Pediatr Res 94, 520–529 (2023).

Elevated human placental heat shock protein 5 is associated with spontaneous preterm birth

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Author: Tissarinen, Pinja1,2; Tiensuu, Heli1,2; Haapalainen, Antti M.1,2;
Organizations: 1PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland
2Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
3Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.4 MB)
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Language: English
Published: Springer Nature, 2023
Publish Date: 2023-05-31


Background: Specific heat shock proteins are associated with pregnancy complications, including spontaneous preterm birth (SPTB). Placental proteomics and whole exome sequencing recently suggested an association between heat shock protein HSPA5 and uncomplicated SPTB. In the present study, we investigated the localization of and possible roles for HSPA5 in SPTB.

Methods: Western blot was performed to validate the result from the previously published proteomic analysis. We used qPCR to assess mRNA expression of genes and immunohistochemistry and immunoelectron microscopy to examine localization of HSPA5 in placental tissue. We silenced the HSPA5 gene in the HTR8/SVneo human trophoblast cell line to investigate possible functions of HSPA5.

Results: HSPA5 was upregulated in placentas from SPTBs compared to spontaneous term births. We did not observe upregulation of HSPA5 mRNA in placental samples. The protein was localized in placental trophoblast in both spontaneous preterm and term placentas. Gene silencing of HSPA5 in human trophoblast cell culture affected the inflammatory response and decreased the expression of several proinflammatory genes.

Conclusions: We suggest that upregulation of HSPA5 in the placenta is associated with spontaneous preterm labor. HSPA5 may promote the inflammatory response and alter the anti-inflammatory state of the placenta which could eventually lead to premature labor.


-We validated upregulation of HSPA5 in placentas from spontaneous preterm birth. HSPA5 was not upregulated at transcriptional level which suggests that it may be regulated post-translationally.

-Silencing HSPA5 in a human trophoblast–derived cell line suggested that HSPA5 promotes expression of proinflammatory cytokines. The emerging inflammation could lead to spontaneous preterm labor.

-Identifying inflammatory pathways and factors associated with spontaneous preterm birth increases knowledge of the molecular mechanisms of premature labor. This could provide cues to predict imminent premature labor and lead to information about how to safely maintain pregnancies.

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Series: Pediatric research
ISSN: 0031-3998
ISSN-E: 1530-0447
ISSN-L: 0031-3998
Volume: 94
Pages: 520 - 529
DOI: 10.1038/s41390-023-02501-9
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Funding: This study was supported by grants from the Jane and Aatos Erkko Foundation (M.H., M.R.), Foundation for Pediatric Research (M.R., A.M.H.), Sigrid Jusélius Foundation (M.H.), Competitive State Research Financing of the Expert Responsibility Area of Oulu University Hospital (M.R.), and Stiftelsen Alma och K. A. Snellman foundation (P.T., H.T., A.M.H.). Open Access funding provided by University of Oulu including Oulu University Hospital.
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