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

  • Schwenkel, George1, 2
  • Romero, Roberto1, 3, 4, 5
  • Slutsky, Rebecca1
  • Motomura, Kenichiro1, 2
  • Hsu, Chaur-Dong1, 2, 6
  • Gomez-Lopez, Nardhy1, 2, 7
  • 1 Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, USA, and Detroit, MI, USA.
  • 2 Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
  • 3 Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA.
  • 4 Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA.
  • 5 Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA.
  • 6 Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA.
  • 7 Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI, USA.
Published Article
The Journal of Maternal-Fetal & Neonatal Medicine
Informa UK (Taylor & Francis)
Publication Date
Dec 01, 2021
DOI: 10.1080/14767058.2019.1706470
PMID: 31906756


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. 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. 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). 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.

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