Dysregulation of an X-linked primate-specific epididymal microRNA cluster in unexplained asthenozoospermia

Xingrong Qing1, Jian Shi1, Tingting Dong1,2

  • 1Family Planning Research Institute/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Oncotarget
|September 17, 2017
PubMed

Insights

Reduced sperm motility, or asthenozoospermia, is a key cause of male infertility. This study identifies specific microRNAs from the epididymis in semen as potential biomarkers for unexplained asthenozoospermia, offering a noninvasive diagnostic approach.

Area of Science:

  • Reproductive biology
  • Epigenetics
  • Male infertility research

Background:

  • Asthenozoospermia, characterized by reduced sperm motility, is a major cause of male infertility, with many cases classified as unexplained (UA).
  • Epididymal epigenetic dysregulation is implicated in sperm maturation defects and asthenozoospermia in animal models.
  • Human epididymal research is limited by tissue accessibility, necessitating alternative methods for studying epididymal function.

Purpose of the Study:

  • To investigate microRNA dysregulation in the epididymis as a potential epigenetic cause of unexplained asthenozoospermia in humans.
  • To establish a noninvasive method for assessing epididymal epigenetic status using cell-free seminal microRNAs.

Main Methods:

  • Screening and validation of cell-free seminal microRNAs in human ejaculate from men with unexplained asthenozoospermia.
  • Analysis of a primate-specific microRNA cluster on the X chromosome known to be expressed in the epididymis.
  • Correlation analysis between microRNA levels and sperm motility parameters.

Main Results:

  • Five specific microRNAs (miR-891b, miR-892b, miR-892a, miR-888, miR-890) were found to be dysregulated in men with unexplained asthenozoospermia.
  • These dysregulated microRNAs belong to a primate-specific, epididymis-specific miRNA cluster on the X chromosome.
  • Coherent dysregulation of this miRNA cluster was observed in 13% of men with UA and significantly correlated with progressive sperm motility.

Conclusions:

  • Dysregulation of this epididymis-specific miRNA cluster may represent an epigenetic basis for a subset of unexplained asthenozoospermia cases.
  • Cell-free seminal microRNAs provide a feasible and noninvasive approach to obtain epigenetic information from the human epididymis.
  • This finding opens new avenues for diagnosing and understanding male infertility related to epididymal dysfunction.

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