Altered microRNA expression profiles of human spermatozoa in patients with different spermatogenic impairments

Capsule:
Microarray and real-time polymerase chain reaction (PCR) studies reveal that microRNAs are differentially expressed in normal versus spermatogenically impaired males and have therapeutic potential for the development of biomarkers for male infertility.

Authors:
Masood Abu-Halima, M.Sc., Mohamad Hammadeh, Prof. Dr., Jana Schmitt, M.Sc., Petra Leidinger, Ph.D., Andreas Keller, Ph.D., Eckart Meese, Prof. Dr., Christina Backes, Ph.D.

Volume 99, Issue 5, Pages 1249-1255.e16, April 2013

Abstract:

Objective:
To determine whether microRNAs are differentially expressed in men with normal versus impaired spermatogenesis, and to find a biomarker for accurate diagnosis of male infertility.

Design:
Microarray with real-time PCR validation.

Setting:
University research and clinical institutes.

Patients:
Male partner of selected couples (n=27), who were undergoing assisted reproduction techniques for infertility treatment.

Interventions:
None.

Main Outcome Measure:
Statistically altered microRNAs expression profiles in normozoospermic versus asthenozoospermic and oligoasthenozoospermic males.

Results:
There were 50 miRNAs up-regulated and 27 miRNAs down-regulated in asthenozoospermic males. In oligoasthenozoospermic males, 42 miRNAs were up-regulated and 44 miRNAs were down-regulated when compared to normozoospermic males. The miRNAs that exhibited the highest fold change and area under the ROC are miR-34b, miR-122 and miR-1973 in samples from asthenozoospermic males and miR-34b, miR-34b*, miR-15b, miR-34c-5p, miR-122, miR-449a, miR-1973, miR-16 and miR-19a in samples from oligoasthenozoospermic males. Furthermore, qRT-PCR assays on specific miRNAs, including miR-141, miR-200a, miR-122, miR-34b, miR-34c-5p and miR-16, yielded results that were largely consistent with the microarray data.

Conclusions:
Our results reveal an extended number of miRNAs, which were differentially expressed in asthenozoospermic and oligoasthenozoospermic males compared to normozoospermic males. This data provides evidence for analysis of miRNA profiles as a future diagnosing tool for male infertility.

  • This work is interesting and addresses an important area in male infertility, the role of post-transcriptional gene regulation. The authors identify 5 novel microRNAs, 2 of which are unique to men with asthenospermia, 2 of which are shared and one of which is unique to men with oligoasthenospermia. Their heatmap demonstrated that the microRNAs could uniquely identify the normal and OA/A groups but could not differentiate the OA and A groups. I wonder whether the authors have data available on the outcomes of the ART used by these patients. The real utility of these tests may lie in their ability to yield information that is not captured by a semen analysis. Regardless, this paper is an important first step in this direction.

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