Clinical chorioamnionitis at term is characterized by changes in the plasma concentration of CHCHD2/MNRR1, a mitochondrial protein

Mariachiara Bosco, Roberto Romero, Dahiana M. Gallo, Manaphat Suksai, Francesca Gotsch, Eunjung Jung, Piya Chaemsaithong, Adi L. Tarca, Nardhy Gomez-Lopez, Marcia Arenas-Hernandez, Arun Meyyazhagan, Malek Al Qasem, Massimo P. Franchi, Lawrence I. Grossman, Siddhesh Aras, Tinnakorn Chaiworapongsa

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Abstract

Objective: Mitochondrial dysfunction was observed in acute systemic inflammatory conditions such as sepsis and might be involved in sepsis-induced multi-organ failure. Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 2 (CHCHD2), also known as Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1), a bi-organellar protein located in the mitochondria and the nucleus, is implicated in cell respiration, survival, and response to tissue hypoxia. Recently, the reduction of the cellular CHCHD2/MNRR1 protein, as part of mitochondrial dysfunction, has been shown to play a role in the amplification of inflammatory cytokines in a murine model of lipopolysaccharide-induced systemic inflammation. The aim of this study was to determine whether the plasma concentration of CHCHD2/MNRR1 changed during human normal pregnancy, spontaneous labor at term, and clinical chorioamnionitis at term. Methods: We conducted a cross-sectional study that included the following groups: 1) non-pregnant women (n = 17); 2) normal pregnant women at various gestational ages from the first trimester until term (n = 110); 3) women at term with spontaneous labor (n = 50); and 4) women with clinical chorioamnionitis at term in labor (n = 25). Plasma concentrations of CHCHD2/MNRR1 were assessed by an enzyme-linked immunosorbent assay. Results: 1) Pregnant women at term in labor with clinical chorioamnionitis had a significantly higher plasma CHCHD2/MNRR1 concentration than those in labor without chorioamnionitis (p =.003); 2) CHCHD2/MNRR1 is present in the plasma of healthy non-pregnant and normal pregnant women without significant differences in its plasma concentrations between the two groups; 3) there was no correlation between maternal plasma CHCHD2/MNRR1 concentration and gestational age at venipuncture; and 4) plasma CHCHD2/MNRR1 concentration was not significantly different in women at term in spontaneous labor compared to those not in labor. Conclusions: CHCHD2/MNRR1 is physiologically present in the plasma of healthy non-pregnant and normal pregnant women, and its concentration does not change with gestational age and parturition at term. However, plasma CHCHD2/MNRR1 is elevated in women at term with clinical chorioamnionitis. CHCHD2/MNRR1, a novel bi-organellar protein located in the mitochondria and the nucleus, is released into maternal plasma during systemic inflammation.

Original languageEnglish
Article number2222333
JournalJournal of Maternal-Fetal and Neonatal Medicine
Volume36
Issue number2
DOIs
StatePublished - 2023

Keywords

  • Bi-organelle protein
  • infection
  • intravascular inflammation
  • labor
  • mitochondrial dysfunction
  • pregnancy

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