HSP70: an alarmin that does not induce high rates of preterm birth but does cause adverse neonatal outcomes

George Schwenkel, Roberto Romero, Rebecca Slutsky, Kenichiro Motomura, Chaur Dong Hsu, Nardhy Gomez-Lopez

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Objective: Preterm labor and birth are strongly associated with sterile intra-amniotic inflammation, a clinical condition that is proposed to be initiated by danger signals, or alarmins. The aim of this study was to investigate whether the intra-amniotic administration of the alarmin heat shock protein 70 (HSP70) induces preterm labor/birth and adverse neonatal outcomes. Methods: Pregnant mice received an intra-amniotic injection of 200 ng (n = 8), 400 ng (n = 6), 500 ng (n = 10), or 1 µg of HSP70 (n = 6). Control mice were injected with saline (n = 10). Following injection, the rates of preterm labor/birth and neonatal mortality were recorded. Neonatal weights at weeks 1, 2, and 3 were also recorded. Results: The intra-amniotic injection of 400 ng [late preterm birth 16.7 ± 16.7% (1/6)], 500 ng [early and late preterm birth 10 ± 10% (1/10) each], or 1 µg [early preterm birth 16.7 ± 16.7% (1/6)] of HSP70 induced low rates of preterm/birth. However, the intra-amniotic injection of 500 ng or 1 µg of HSP70 induced significantly higher rates of neonatal mortality compared to controls [saline 14.2% (10/74), 200 ng 9.8% (6/61), 400 ng 17.9% (9/45), 500 ng 28.8% (23/78), and 1 µg 21.4% (13/49)]. Neonates born to dams injected with 200, 500 ng, or 1 µg HSP70 were leaner than controls (p ≤.05). Conclusion: Intra-amniotic administration of the alarmin HSP70 did not induce high rates of preterm labor/birth; yet, it did indeed result in adverse neonatal outcomes.

Original languageEnglish (US)
Pages (from-to)4110-4118
Number of pages9
JournalJournal of Maternal-Fetal and Neonatal Medicine
Volume34
Issue number24
DOIs
StatePublished - 2021
Externally publishedYes

Keywords

  • Acute histologic chorioamnionitis
  • DAMPs
  • amniotic fluid
  • fetal inflammatory response
  • funisitis
  • inflammation
  • mouse
  • parturition
  • pregnancy
  • prematurity
  • sterile intra-amniotic inflammation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

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