Promising novel biomarkers and therapy targets: The application of cell-free seminal nucleotides in male reproduction research

  • Hui-Min Li
    Guilin Medical University, Guilin, 541004, P. R. China
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  • Xiao-Yan Wan
    Department of Obstetrics and gynecology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510620, P. R. China
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  • Jie-Yi Zhao
    Institute of Reproductive Health/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P. R. China
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  • Xu-Ming Liang
    Affiliated Hospital of Guilin Medical University, Guilin, 541001, P. R. China
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  • Yun Dai
    Affiliated Hospital of Guilin Medical University, Guilin, 541001, P. R. China
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  • Hong-Gang Li
    Correspondence to: Hong-Gang Li, PhD, Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, P. R. China. Tel.: +86 27 83692651; Fax.: +86 27 83692651.
    Institute of Reproductive Health/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P. R. China

    Wuhan Tongji Reproductive Medicine Hospital, Wuhan, 430030, P. R. China
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Published:December 28, 2022DOI:


      Liquid biopsy has the advantage of diagnosing diseases in a non-invasive manner. Seminal plasma contains secretions from the bilateral testes, epididymides, seminal vesicles, bulbourethral glands, and the prostate. These organs are relatively small and contain delicate tubes that are prone to damage by invasive diagnosis. Cell-free seminal nucleic acids test is a newly emerged item in liquid biopsy. Here, we present a comprehensive overview of all known cell-free DNA and cell-free RNAs (mRNA, miRNA, lncRNA, circRNA, piRNA, YRNA, tsRNA, etc.) and discuss their roles as biomarker candidates in liquid biopsy. With great advantages, including high stability, sensitivity, representability, and non-invasiveness, cell-free DNA/RNAs may be developed as promising biomarkers for the screening, diagnosis, prognosis, and follow-up of diseases in semen-secreting organs. Moreover, RNAs in semen may participate in important processes, including sperm maturation, early embryo development, and transgenerational disease inheritance, which may be developed as potential treatment targets for future clinical use.

      Key words


      cf-NA (cell-free DNAs/RNAs), cfs-NA (cell-free seminal DNAs/RNAs), NOA (non-obstructive azoospermia), SCOS (sertoli-cell syndrome), MA (maturation arrest), HO (hypospermatogenesis), SMV (seminal microvesicles), SE (seminal exosome), MF (microfilter), UF (ultrafilter)
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