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

Pinja Tissarinen, Heli Tiensuu, Antti M. Haapalainen, Tomi A. Määttä, Marja Ojaniemi, Mikko Hallman, Mika Rämet

    Research output: Contribution to journalArticleScientificpeer-review

    1 Citation (Scopus)
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    Abstract

    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. Impact: 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.

    Original languageEnglish
    Pages (from-to)520-529
    Number of pages10
    JournalPediatric Research
    Volume94
    Issue number2
    Early online dateFeb 2023
    DOIs
    Publication statusPublished - 2023
    Publication typeA1 Journal article-refereed

    Publication forum classification

    • Publication forum level 2

    ASJC Scopus subject areas

    • Pediatrics, Perinatology, and Child Health

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