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. 2023 Dec;36(2):2222333.
doi: 10.1080/14767058.2023.2222333.

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

Mariachiara Bosco  1   2   3 , Roberto Romero  1   4   5 , Dahiana M Gallo  1   2   6 , Manaphat Suksai  1   2   7 , Francesca Gotsch  1   2 , Eunjung Jung  1   2   8 , Piya Chaemsaithong  1   2   9 , Adi L Tarca  1   2   10   11 , Nardhy Gomez-Lopez  1   2   11   12 , Marcia Arenas-Hernandez  1   2 , Arun Meyyazhagan  1   2   13 , Malek Al Qasem  1   2   14 , Massimo P Franchi  3 , Lawrence I Grossman  1   11 , Siddhesh Aras  1   11 , Tinnakorn Chaiworapongsa  1   2
Affiliations

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

Mariachiara Bosco et al. J Matern Fetal Neonatal Med. 2023 Dec.

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.

Keywords: Bi-organelle protein; infection; intravascular inflammation; labor; mitochondrial dysfunction; pregnancy.

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Figures

Figure 1.
Figure 1.
Plasma concentration (pg/ml) of CHCHD2/MNRR1 in non-pregnant and normal pregnant women [723 (584-5217) pg/mL vs. 747 (477-4668) pg/mL pg/mL]. Data are reported as the median and as the interquartile range. The y-axis is in logarithmic scale.
Figure 2.
Figure 2.
Plasma CHCHD2/MNRR1 concentration (pg/ml) of pregnant women at term not in labor and those at term in spontaneous labor [1038 (527-9834) pg/mL vs. 819 (515-4773]. Data are reported as the median and as the interquartile range. The y-axis is in logarithmic scale.
Figure 3.
Figure 3.
Plasma CHCHD2/MNRR1 concentration (pg/ml) of pregnant women at term in labor without and with clinical chorioamnionitis [819 (515-4773) pg/mL vs1722 (1201-3757) pg/mL]. Data are reported as the median and as the interquartile range. The y-axis is in logarithmic scale.
See this image and copyright information in PMC

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