Sperm microRNA pairs: new perspectives in the search for male fertility biomarkers

Expression levels of sperm microRNA pairs can be used as fertility biomarkers in patients with seminal alterations and patients with unexplained male infertility.

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Volume 112, Issue 5, Pages 831–841


Celia Corral-Vazquez, M.Sc., Albert Salas-Huetos, Ph.D., Joan Blanco, Ph.D., Francesca Vidal, Ph.D., Zaida Sarrate, Ph.D., Ester Anton, Ph.D.



To identify candidates of fertility biomarkers among pairs of human sperm microRNAs.


Expression data of 736 sperm microRNAs from fertile and infertile individuals characterized in previous published studies by means of TaqMan quantitative polymerase chain reaction (PCR) were reexamined. A set of microRNA pairs with the best biomarker potential were selected and validated by means of quantitative real-time (qRT) PCR in an independent cohort.


University laboratory.


Semen samples were obtained from fertile (n = 10) and infertile (asthenozoospermia, n = 10; teratozoospermia, n = 10; oligozoospermia, n = 10; unexplained male infertility [UMI], n = 8) individuals. The validation cohort included 9 fertile donors and 14 infertile patients with different seminal alterations.



Main Outcome Measure(s)

Spearman test was used to select microRNA pairs with a correlated expression in fertile individuals and a noncorrelated expression in each infertile group. The biomarker potential of these pairs was determined with the use of receiver operating characteristic curves. The differential relative expression of each pair in fertile and infertile populations was verified (Mann-Whitney test). Those pairs with best results were validated by qRT-PCR.


Forty-eight pairs showed significant correlations in the fertile group. The pairs that were uncorrelated in the infertile populations and displayed the best biomarker potential were hsa-miR-942-5p/hsa-miR-1208 (asthenozoospermia), hsa-miR-296-5p/hsa-miR-328-3p (teratozoospermia), hsa-miR-139-5p/hsa-miR-1260a (oligozoospermia), and hsa-miR-34b-3p/hsa-miR-93-3p (UMI). The hsa-miR-942-5p/hsa-miR-1208 pair showed the greatest potential for detecting seminal alterations in the validation cohort (85.71% true positives).


The pairs hsa-miR-942-5p/hsa-miR-1208 and hsa-miR-34b-3p/hsa-miR-93-3p have the potential to become new molecular biomarkers that could help to diagnose male infertility, especially in cases of UMI or when seminal parameters are close to the threshold values.

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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. 


Go to the profile of Mary Samplaski
about 2 years ago

This is compelling data showing that there are likely many genetic causes for male infertility outside of the currently available options. Did the authors look at individual semen parameters and did they see any correlations between individual gene abnormalities and semen abnormalities (ie gene x correlated with poor motility, gene y correlated with poor counts)? It may have been difficult with the small sample size.