Inhibition of eIF5A Results in Aberrant Uterine Natural Killer Cell Function and Embryo Loss in Mice

Authors

  • Xiaoli Qin,

    1. Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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    • These authors are equally contributed to this work.
  • Xiaorui Liu,

    1. International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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    • These authors are equally contributed to this work.
  • Bin Shan,

    1. Medical Sciences, Washington State University Spokane, Spokane, WA, USA
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  • Lijuan Shi,

    1. Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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  • Surendra Sharma,

    1. Department of Pediatrics, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA
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  • Ji Wu,

    1. Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
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  • Yi Lin

    Corresponding author
    1. Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
    2. International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
    • Correspondence

      Yi Lin, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.

      E-mail: yilinonline@126.com

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Abstract

Problem

The role of eukaryotic initiation factor 5A (eIF5A) in feto-maternal immunotolerance is poorly understood.

Methods of study

The effects of N1-guanyl-1,7-diaminoheptane (GC7), an inhibitor of eIF5A, on the proportion and function of natural killer (NK) cell subsets were investigated using flow cytometry, immunofluorescence, CCK8 assay, TUNEL assay, DNA fragmentation analysis, mitochondrial membrane potential assay, and Western blotting.

Results

Inhibition of eIF5A by GC7 increased embryo loss and reduced the percentage of NK cells in the uterus and spleen. GC7 treatment caused inhibition of NK cell proliferation in a time- and dose-dependent manner. GC7 also induced apoptosis of NK cells. GC7 treatment increased the protein levels of FasL, bax, p53, and cleaved caspase-3. Moreover, GC7 caused loss of mitochondrial membrane potential in NK cells.

Conclusion

Inhibition of eIF5A results in aberrant NK cell function and increased embryo loss.

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