Differential expression of miR-23a/b-3p and its target genes in male patients with subfertility

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Authors:

Masood Abu-Halima, Ph.D., Basim M. Ayesh, Ph.D., Martin Hart, Ph.D., Julia Alles, Ph.D., Ulrike Fischer, Ph.D., Mohamad Hammadeh, Prof. Dr., Andreas Keller, Prof. Dr., Mahmoud Huleihel, Prof. Dr., Eckart Meese, Prof. Dr.

Abstract:

Objective

To elucidate the potential regulatory function of miR-23a/b-3p on spermatogenesis-specific genes.

Design

Reverse transcription quantitative polymerase chain reaction (RT-qPCR) validation, Northern blot, dual luciferase assay, and Western blot confirmation.

Setting

University research and clinical institutes.

Patient(s)

A total of 115 men presenting at an infertility clinic.

Intervention(s)

None.

Main Outcome Measure(s)

Significant higher abundance levels of miR-23a/b-3p and lower abundance levels of PFKFB4, HMMR, SPATA6,and TEX15 in oligoasthenozoospermic men compared with those in normozoospermic men.

Result(s)

In oligoasthenozoospermic men, the abundance levels of miR-23a/b-3p were significantly higher when compared with controls as determined by RT-qPCR. After in silico prediction of potential targets of miR-23a/b-3p, PFKFB4, HMMR, SPATA6, and TEX15 have been identified as direct targets by dual luciferase assays. Mutations in the miR-23a/b-3p binding site within the 3′UTRs resulted in abrogated responsiveness to miR-23a/b-3p. PFKFB4, HMMR, SPATA6, and TEX15 mRNA and HMMR and SPATA6 protein levels were significantly lower in oligoasthenozoospermic men compared with in normozoospermic men. Correlation analysis showed that the sperm count, motility, and morphology were negatively correlated with miR-23a/b-3p and positively correlated with PFKFB4, HMMR, SPATA6, and TEX15 abundance levels (lower ΔCt, the higher abundance levels).

Conclusion(s)

This study establishes a link between up-regulation of miR-23a/b-3p and the coincident down-regulation of four expressed genes in the sperm of men with oligoasthenozoospermia, compared with men with normozoospermia. This study provides a novel insight into some of the mechanisms leading to male subfertility, offering a possible therapeutic target for treatment, or even for male contraception.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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