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PRSS55 is a novel potential causative gene for human male infertility

  • Man Liu
    Affiliations
    Department of Obstetrics and Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
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  • Chuan Jiang
    Affiliations
    Department of Obstetrics and Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
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  • Xueguang Zhang
    Affiliations
    Department of Obstetrics and Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
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  • Guohui Zhang
    Affiliations
    Department of Obstetrics and Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
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  • Mohan Liu
    Affiliations
    Department of Obstetrics and Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China

    State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China
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  • Rui Zheng
    Affiliations
    Department of Obstetrics and Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
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  • Yihong Yang
    Correspondence
    Corresponding authors.
    Affiliations
    Reproduction Medical Center of West China Second University Hospital, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu 610041, China
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  • Ying Shen
    Correspondence
    Corresponding authors.
    Affiliations
    Department of Obstetrics and Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
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      Abstract

      Research question

      Testis-specific PRSS55 is a chymotrypsin-like serine protease that is highly conserved among mammalian species. The essential role of Prss55 in mouse male fertility has been established. What is the role of PRSS55 in human reproduction?

      Design

      Whole exome sequencing was used to identify the genetic cause in an infertile male with teratozoospermia. Papanicolaou staining, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to explore morphological defects in the patient's spermatozoa. Immunofluorescence staining and western blot analysis were conducted to assess the pathogenicity of the identified variant. Intracytoplasmic sperm injection (ICSI) was used to assist the patient with fertilization.

      Results

      Sanger sequencing of the pedigree demonstrated that the infertile man carried a novel homozygous mutation in PRSS55 (c.575C>T [p.A192V]). Morphological defects in the sperm head, neck, midpiece and tail were demonstrated by Papanicolaou staining, SEM and TEM. Immunofluorescence staining and western blotting of the patient's spermatozoa showed that the point mutation changed the conformation of PRSS55 and caused a sharp decrease in the PRSS55 protein concentration. The expression and subcellular localization of PRSS55 in the testis and spermatozoa of mice and humans showed that PRSS55 was expressed in the head and flagella of spermatids and epididymal spermatozoa. Moreover, ICSI treatment for this kind of infertile patient was shown to be effective.

      Conclusions

      These findings revealed a novel mutation in PRSS55 in an infertile patient, suggesting for the first time the crucial role of PRSS55 in human fertility. This study provides new insight into genetic counselling diagnoses and subsequent treatment for male infertility.

      Keywords

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      Biography

      Man Liu is part of the scientific research staff at the Department of Obstetrics and Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases, Sichuan University, Chegdu, China. Her main research topic is the pathogenesis of male infertility.
      Key message
      Testis-specific PRSS55 plays an important role in male mouse reproduction, but there is a lack of knowledge relating to PRSS55 in human reproduction. This is the first report of an infertile man carrying a novel homozygous mutation in PRSS55 (c.575C>T [p.A192V]), suggesting that PRSS55 may be a potential causative gene for human male infertility.