Panel of five microRNAs as potential biomarkers for the diagnosis and assessment of male infertility

Capsule:
Quantitative real-time polymerase chain reaction validation reveals that a set of five miRNAs deserves to be used as a diagnostic test along with other routine clinical tests, such as conventional semen and histologic analysis, to improve male infertility assessment and diagnosis.

Authors:
Masood Abu-Halima, M.Sc., Mohamad Hammadeh (Prof.Dr.), Christina Backes, Ph.D., Ulrike Fischer, Ph.D., Petra Leidinger, Ph.D., Abdel Monem Lubbad, M.D., Andreas Keller (Prof.Dr.), Eckart Meese (Prof.Dr.)

Volume 102, Issue 4, Pages 989-997

Abstract:

Objective:
To validate a set of five microRNAs (miRNAs) as specific biomarkers for the assessment of male infertility.

Design:
Quantitative real-time polymerase chain reaction (qRT-PCR) validation study.

Setting:
University research and clinical institutes.

Patient(s):
Two hundred twenty-six men presenting at an infertility clinic.

Intervention(s):
None.

Main Outcome Measure(s):
Validation analysis of a set of miRNAs in human purified spermatozoa and testicular biopsies.

Result(s):
Five miRNAs (hsa-miR-34b*, hsa-miR-34b, hsa-miR-34c-5p, hsa-miR-429, and hsa-miR-122) were confirmed with the use of qRT-PCR analysis in validation sets in patients with different forms of spermatogenic impairments (subfertile and nonobstructive azoospermia [NOA]) and control subjects. We found that hsa-miR-429 was significantly increased and the four other miRNAs were decreased in both tested groups compared with normal control subjects. Computing the area under the receiver operating characteristic curve (AUC) value for each of the five miRNAs, we showed that they separated the tested groups with high accuracy (range 0.777–0.988), except for hsa-miR-429 (AUC 0.475), in patient samples with NOA. Furthermore, with the use of support vector machine classification combining these five miRNAs, we found that they discriminated individuals with, respectively, subfertility and NOA from control subjects with an accuracy of 98.65% and 99.91%, a specificity of 98.44% and 99.69%, and a sensitivity of 98.83% and 100%.

Conclusion(s):
Our finding suggests that these five miRNAs have potential as novel noninvasive biomarkers to diagnose patients with subfertility. Except for hsa-miR-429, the combination of these miRNAs with other conventional tests would improve the diagnostic accuracy for detecting patients with different forms of NOA.

  • ranjithrama

    It is interesting that mi-RNA’s can be used as biomarkers for diagnosis of infertility. Usually diagnosis of NOA vs. oligospermia is fairly obvious. We can be 90% certain about azoospermia due to sperm production defect based on FSH and testis volume (Schoor & Niederberger 2002). Where mi-RNA’s need to be utilized is in their ability to distinguish men that have SCO vs. maturation arrest vs. hypospermatogenesis on testis biopsy. It could also be used to distinguish men with focal areas of spermatogenesis on TESE.

  • MJMV

    Hello…I would just like to note that two of these five were previously identified as being misexpressed in sterile male Xenopus (Madison-Villar and Michalak, 2012; miR-34 and miR-122, though the 2012 study identified miR-34a, rather than miR-34b. However, since these two mature miRNA differ by only one of 11 bp at the 5′ terminus, xtr-miR-34a should be capable of binding the same targets, albeit with perhaps slightly less efficiency). Your confirmation of these miRNA as putative biomarkers for male sterility is quite astounding, IMO. Given the ease with which sterile male frogs can be generated and maintained, I am left wondering if the Xenopus system may prove to be of value for future studies regarding male sterility/fertility.

    • Masood

      Hello MJMV thanks for your kind notification, Kindly note that
      these miRNAs were showed a high expression value when we compared infertile and
      sub-fertile to control normal by both microarray and qRT-PCR validation and
      confirmation.

      In
      addition, all of these 5 miRNAs were known to be expressed in seminiferous
      epithelium cell types (pachytene spermatocytes,
      round spermatids,elongating spermatids, and Sertoli cells) and somatic cells,
      we showed that in our previous publications which based only on profiling
      analysis and by others based on experimental functional analysis.

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