PiRNAs interacting proteins, candidate molecular marker for evaluation of idiopathic male infertility.

Abstract

Piwi-interacting RNAs (piRNAs) are a new class of non-coding single-stranded small RNAs molecules (24-31 nt)that play crucial regulatory roles in several biological pro-cesses such as germ line stem cell development in sper-matogenesis, epigenetic changes and transposon silencing.They are originated from specific human genome regionsthat consist of transposable elements and repetitive ele-ments. Contradictory to micro-RNAs maturation, the piR-NAs are maturated by a Dicer-independent mechanism andinteract with PIWI subfamily of Argonaute family proteins(Siomi et al., 2011). Importantly, any biological roles ofpiRNAs depended to formation of piRNAs and PIWI pro-teins complex. After processing of this complex, lead totransposable element suppresses and protection of muta-genesis. In general, expression and mobilisation of trans-posable elements process by two different mechanismsincluding cleavage of transposable element transcripts andheterochromatin-mediated gene silencing (Farazi et al.,2008). However, with considering of the essential roles ofpiRNAs to protection of human genome against transpos-able elements which move and replicate inter-genome ofregions, it is conceivable that play a important roles in par-ticular stages of spermatogenesis process especially in germline cells development. Surprisingly, the piRNAs are mole-cules that frequently presented in spermatocyte and sper-matid cells during spermatogenesis.Of note, PIWI subfamilies of Argonaut proteins suchas HIWI, HIWI2, HIWI3 and HILI have key functionsin transposon silencing pathways. Moreover, several ofthese proteins are expressed in male gonad in specifi-cally and showing biological functions in the germ linedevelopment (Carmell et al., 2007). Furthermore, anydeficiency of these proteins maybe leads to aberrantmale germ line cells development during spermatogene-sis. Unfortunately, to date, the investigators could notbe revealed all of the aetiologies that lead to spermato-genic failure, and many factors are remained unknown.In general, a significant proportion of idiopathic maleinfertility is associated with severe oligozoospermia andazoospermia although the most common alterationsthat occur in azoospermia factor regions (AZFa, AZFband AZFc) may result in sperm production failure andlead to male infertility (Ghorbian, 2012). However, Guet al. (2010) revealed that several piwi subfamily ofproteins play an important role in normal spermato-genesis. They evaluated piwi gene polymorphisms inpatients with idiopathic azoospermia and oligozoosper-mia, and findings showed some of single-nucleotidepolymorphisms (SNPs) in piwi genes, significantly asso-ciated with a risk of oligozoospermia and azoospermia.However, herein, we speculate that with considering ofproteins that contributed in the piRNAs pathway maybe introduced as a new molecular marker for idiopathicazoospermia and oligozoospermia infertile male analysis.Thereafter, it is conceivable that evaluation of piRNAsand associated proteins opened new opportunity fordetermination of idiopathic infertility.A. Poursadegh ZonouziBiotechnology Research Center, Tabriz University ofMedical Sciences, Tabriz, IranA. A. Poursadegh ZonouziDepartment of Genetics and Medical Biotechnology, Facultyof Medicine, Hormozgan University of Medical Sciences,Bandar Abbas, IranS. GhorbianDepartment of Biology, Science and Research Branch,Islamic Azad University, Tehran, IranE-mails: ghorbian20@yahoo.com; s.ghorbian@srbiau.ac.irReferencesCarmell MA, Girard A, van de Kant HJ, Bourc’his D, BestorTH, de Rooij DG, Hannon GJ (2007) MIWI2 is essential forspermatogenesis and repression of transposons in the mousemale germline. Dev Cell 12:503–514.Farazi TA, Juranek SA, Tuschl T (2008) The growing catalogof small RNAs and their association with distinctArgonaute/Piwi family members. Development 135:1201–1214.Gu A, Ji G, Shi X, Long Y, Xia Y, Song L, Wang S, Wang X(2010) Genetic variants in Piwi-interacting RNA pathwaygenes confer susceptibility to spermatogenic failure in aChinese population. Hum Reprod 25:2955–2961.Ghorbian S (2012) Routine diagnostic testing of Y chromo-some deletions in male infertile and subfertile. Gene503:160–164.Siomi MC, Sato K, Pezic D, Aravin AA (2011) PIWI-interact-ing small RNAs: the vanguard of genome defence. NatureRev Mol Cell Biol 12:246–258.