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Updated: Feb 22, 2026

Analysis of Epididymal Protein Synthesis and Secretion
Published on: August 25, 2018
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.
Abstract:
Asthenoszoopermia, characterized by reduced sperm motility, is one of the primary forms of male infertility. Whereas most cases were diagnosed into unexplained asthenozoospermia (UA) because the etiology cannot be identified. In animal models, epigenetic dysregulation in epididymis can impair sperm maturation and result in asthenozoospermia. However, researches of epididymal epigenetic regulation on humans are impeded by the difficulty in obtaining epididymal tissues. We previously identified cell-free seminal microRNAs predominately derived from epididymis in human ejaculate. In the present study, these microRNAs were used to screen and validate the microRNA dysregulation in men with UA, which were divided into screening set and validation set. The expression of five miRNAs (miR-891b, miR-892b, miR-892a, miR-888 and miR-890) was found and confirmed to be dysregulated in men with UA. Interestingly, these five miRNAs belong to a primate-specific miRNA cluster located on the X chromosome with epididymis specific expression. Moreover, obvious coherent dysregulation of these miRNAs were observed in 13% men with UA. Regression analysis demonstrated that levels of these miRNAs were significantly correlated with progressive sperm motility. Functions and pathways of predicted target genes of this cluster suggested its role in sperm maturation. Dysregulation of this miRNA cluster might be an epigenetic basis for some patients with UA. We also showed a noninvasive and feasible approach to get epigenetic information of human epididymis.
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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