The MNRR1 activator nitazoxanide abrogates lipopolysaccharide-induced preterm birth in mice

Neeraja Purandare; Nardhy Gomez-Lopez; Marcia Arenas-Hernandez; Jose Galaz; Roberto Romero; Yue Xi; Andrew M Fribley; Lawrence I Grossman; Siddhesh Aras

doi:10.1016/j.placenta.2023.07.005

The MNRR1 activator nitazoxanide abrogates lipopolysaccharide-induced preterm birth in mice

Placenta. 2023 Sep 7:140:66-71. doi: 10.1016/j.placenta.2023.07.005. Epub 2023 Jul 8.

Authors

Neeraja Purandare¹, Nardhy Gomez-Lopez², Marcia Arenas-Hernandez³, Jose Galaz³, Roberto Romero⁴, Yue Xi⁵, Andrew M Fribley⁵, Lawrence I Grossman⁶, Siddhesh Aras¹

Affiliations

¹ Pregnancy 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 (NICHD/NIH/DHHS), Bethesda, MD 20892, USA; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, 48201, USA.
² Pregnancy 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 (NICHD/NIH/DHHS), Bethesda, MD 20892, USA; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, 48201, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, 48201, USA; Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
³ Pregnancy 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 (NICHD/NIH/DHHS), Bethesda, MD 20892, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
⁴ Pregnancy 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 (NICHD/NIH/DHHS), Bethesda, MD 20892, USA; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, 48104, USA; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, 48824, USA.
⁵ Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
⁶ Pregnancy 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 (NICHD/NIH/DHHS), Bethesda, MD 20892, USA; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, 48201, USA. Electronic address: lgrossman@wayne.edu.

PMID: 37544161
PMCID: PMC10529525 (available on 2024-09-07)
DOI: 10.1016/j.placenta.2023.07.005

Abstract

Intra-amniotic inflammation leading to preterm birth is one of the leading causes of neonatal morbidity and mortality. We recently reported that the mitochondrial levels of MNRR1 (Mitochondrial Nuclear Retrograde, Regulator 1; also called CHCHD2, AAG10, or PARK22), an important bi-organellar regulator of cellular function, are reduced in the context of inflammation and that genetic and pharmacological increases in MNRR1 levels can counter the inflammatory profile. Herein, we show that nitazoxanide, a clinically approved drug, is an activator of MNRR1 and abrogates preterm birth in a well-characterized murine model caused by intra-amniotic lipopolysaccharide (LPS) injection.

Keywords: CHCHD2; Decidua; Intra-amniotic infection; Intra-amniotic inflammation; Nitazoxanide (Alinia); Prematurity; Preterm labor.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Amniotic Fluid
Animals
Chorioamnionitis*
DNA-Binding Proteins
Female
Humans
Infant, Newborn
Inflammation / chemically induced
Lipopolysaccharides
Mice
Nitro Compounds / adverse effects
Premature Birth* / prevention & control
Transcription Factors / genetics

Substances

Lipopolysaccharides
nitazoxanide
Nitro Compounds
CHCHD2 protein, human
DNA-Binding Proteins
Transcription Factors

Grants and funding

HHSN275201300006C/HD/NICHD NIH HHS/United States