Original Article Regulatory Functions of MicroRNAs in Male Reproductive Health: A New Approach to Understanding Male Infertility Asghar Beigi Harchegani 1 , Hossein Shafaghatian 1 , Eisa Tahmasbpour 2 , and Alireza Shahriary 1 Abstract MicroRNAs (miRNAs) are a novel class of small noncoding RNAs (ncRNAs) that play critical roles in regulation of gene expression, especially at posttranscriptional level. Over the past decade, the degree to which miRNAs are involved in male infertility has become clear. They are expressed in a cell- or phase-specific manner during spermatogenesis and play crucial role in male reproductive health. Therefore, dysregulation of miRNAs in testicular cells can be considered as a molecular basis for reproductive failure and male infertility. The abnormal expression pattern of miRNAs can be transmitted to the offspring via assisted reproductive techniques (ART) and results in the birth of children with a higher risk of infertility, congenital abnormalities, and morbidity. This review expounds on the miRNAs reported to play essential roles in somatic cells development, germ cells differentiation, steroidogenesis, normal spermatogenesis, sperm maturation, and male infertility, as well as emphasizes their importance as minimally invasive biomarkers of male infertility. Keywords miRNAs, spermatogenesis, male infertility, germ cells, somatic cells Introduction Human infertility is now considered as one of the significant health problems that affect almost 10% to 15% of couples throughout the world, 1 and among them, male factors play a role in approximately half of all infertile couples. 2 Male infer- tility is a multifactorial syndrome that can result from a wide variety of disorders. 3 Numerous factors including varicocele, 1 hyperviscosity semen, 4 testicular failure, 5 vesicular damage due to torsion, 6 obstruction of testicular sperm passage and ejaculatory failures, 7 testicular cancer, 8 endocrinological dis- orders, 9 impaired spermatogenesis, 10 genital tract infection, and immunological factors 11,12 are now considered as a major cause of male infertility. Besides, prolonged exposure to heat, 13 environmental agents such as pesticides, 14,15 occupational exposure to radiation and magnetic waves, 16 chemother- apy, 17,18 electronic devices, 19 heavy metals, 20 obesity, 21 aging, 22 opiate using, smoking and alcohol consumption, 23 dietary deficiency of some trace elements, and lifestyle 24 can affect spermatogenesis and sperm maturation and lead male fertility or subinfertility. Infertile men with normal investiga- tions and unexplained infertility are categorized as idiopathic infertile. 3 It can be resulted by different factors such as oxida- tive stress induced by reactive oxygen species (ROS), sperm DNA fragmentation, and molecular genetic abnormalities. 3,25 Molecular genetic anomalies are very important in etiology of male infertility, as they are responsible for 15% to 30% of cases, especially those involving the Y chromosome. 3 The molecular genetic basis of male infertility is still unclear; however, numerous studies have revealed the close relationship between noncoding RNAs (ncRNAs) and male infertility. The ncRNAs are small and noncoding regions (greater than 90%) in human genome that make up much of the RNA content of cells and have the potential to regulate gene expression and many biological processes. 3 MicroRNAs (miR- NAs) are a class of ncRNAs that regulate male germ cells differentiation, spermatogenesis, sperm maturation, sperm function, and male fertility. Some miRNAs are preferentially expressed in certain type of male germ cells, while the others 1 Chemical Injuries Research Center, System Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 2 Laboratory of Regenerative Medicine and Biomedical Innovations, Pasteur Institute of Iran, Tehran, Iran Corresponding Authors: Alireza Shahriary, Chemical Injuries Research Center, System Biology and Poisonings Institute, Baqiatallah University of Medical Sciences, P.O. Box 19945-581, Tehran, Iran. Email: shahriary961@gmail.com Eisa Tahmasbpour, Laboratory of Regenerative Medicine and Biomedical Innovations, Pasteur Institute of Iran, Tehran, Iran. Email: tahmasb62@gmail.com Reproductive Sciences 1-11 ª The Author(s) 2018 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/1933719118765972 journals.sagepub.com/home/rsx