Evidence for the participation of CHCHD2/MNRR1, a mitochondrial protein, in spontaneous labor at term and in preterm labor with intra-amniotic infection
Issued Date
2023-01-01
Resource Type
ISSN
14767058
eISSN
14764954
Scopus ID
2-s2.0-85150652162
Pubmed ID
36941246
Journal Title
Journal of Maternal-Fetal and Neonatal Medicine
Volume
36
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Maternal-Fetal and Neonatal Medicine Vol.36 No.1 (2023)
Suggested Citation
Bosco M., Romero R., Gallo D.M., Suksai M., Gotsch F., Jung E., Chaemsaithong P., Tarca A.L., Gomez-Lopez N., Arenas-Hernandez M., Meyyazhagan A., Al Qasem M., Franchi M.P., Grossman L.I., Aras S., Chaiworapongsa T. Evidence for the participation of CHCHD2/MNRR1, a mitochondrial protein, in spontaneous labor at term and in preterm labor with intra-amniotic infection. Journal of Maternal-Fetal and Neonatal Medicine Vol.36 No.1 (2023). doi:10.1080/14767058.2023.2183088 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82551
Title
Evidence for the participation of CHCHD2/MNRR1, a mitochondrial protein, in spontaneous labor at term and in preterm labor with intra-amniotic infection
Author's Affiliation
Universidad del Valle, Cali
Azienda Ospedaliera Universitaria Integrata Verona
Mutah University
University of Michigan Medical School
Michigan State University
Wayne State University School of Medicine
National Institute of Child Health and Human Development (NICHD)
Mahidol University
Wayne State University
Università degli Studi di Perugia
Azienda Ospedaliera Universitaria Integrata Verona
Mutah University
University of Michigan Medical School
Michigan State University
Wayne State University School of Medicine
National Institute of Child Health and Human Development (NICHD)
Mahidol University
Wayne State University
Università degli Studi di Perugia
Other Contributor(s)
Abstract
Objective: Intra-amniotic inflammation (IAI), associated with either microbe (infection) or danger signals (sterile), plays a major role in the pathophysiology of preterm labor and delivery. Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 2 (CHCHD2) [also known as Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1)], a mitochondrial protein involved in oxidative phosphorylation and cell survival, is capable of sensing tissue hypoxia and inflammatory signaling. The ability to maintain an appropriate energy balance at the cellular level while adapting to environmental stress is essential for the survival of an organism. Mitochondrial dysfunction has been observed in acute systemic inflammatory conditions, such as sepsis, and is proposed to be involved in sepsis-induced multi-organ failure. The purpose of this study was to determine the amniotic fluid concentrations of CHCHD2/MNRR1 in pregnant women, women at term in labor, and those in preterm labor (PTL) with and without IAI. Methods: This cross-sectional study comprised patients allocated to the following groups: (1) mid-trimester (n = 16); (2) term in labor (n = 37); (3) term not in labor (n = 22); (4) PTL without IAI who delivered at term (n = 25); (5) PTL without IAI who delivered preterm (n = 47); and (6) PTL with IAI who delivered preterm (n = 53). Diagnosis of IAI (amniotic fluid interleukin-6 concentration ≥2.6 ng/mL) included cases associated with microbial invasion of the amniotic cavity and those of sterile nature (absence of detectable bacteria, using culture and molecular microbiology techniques). Amniotic fluid and maternal plasma CHCHD2/MNRR1 concentrations were determined with a validated and sensitive immunoassay. Results: (1) CHCHD2/MNRR1 was detectable in all amniotic fluid samples and women at term without labor had a higher amniotic fluid CHCHD2/MNRR1 concentration than those in the mid-trimester (p = 0.003); (2) the amniotic fluid concentration of CHCHD2/MNRR1 in women at term in labor was higher than that in women at term without labor (p = 0.01); (3) women with PTL and IAI had a higher amniotic fluid CHCHD2/MNRR1 concentration than those without IAI, either with preterm (p < 0.001) or term delivery (p = 0.01); (4) women with microbial-associated IAI had a higher amniotic fluid CHCHD2/MNRR1 concentration than those with sterile IAI (p < 0.001); (5) among women with PTL and IAI, the amniotic fluid concentration of CHCHD2/MNRR1 correlated with that of interleukin-6 (Spearman’s Rho = 0.7; p < 0.001); and (6) no correlation was observed between amniotic fluid and maternal plasma CHCHD2/MNRR1 concentrations among women with PTL. Conclusion: CHCHD2/MNRR1 is a physiological constituent of human amniotic fluid in normal pregnancy, and the amniotic concentration of this mitochondrial protein increases during pregnancy, labor at term, and preterm labor with intra-amniotic infection. Hence, CHCHD2/MNRR1 may be released into the amniotic cavity by dysfunctional mitochondria during microbial-associated IAI.