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Genes involved in piwi-interacting RNAs (piRNAs) pathway have an essential role in spermatogenesis. HIWI and TDRD proteins are critical for piRNA biogenesis and function. Therefore, Mutations and polymorphisms in  HIWI  and  TDRD  genes may play role in male infertility. The aim of the present study was to investigate the role of  HIWI2  rs508485 (T&gt;C) and  HIWI3  rs11703684 (C&gt;T) polymorphisms and mutational analysis of TDRD5 gene in idiopathic non-obstructive azoospermia in a case-control study including 226 non-obstructive azoospermia patients and 200 fertile males. Genotyping for both polymorphisms was performed using Tetra-Primer ARMS PCR. Mutation analysis of  TDRD5  gene was done using multi-temperature single strand conformation polymorphism technique (MSSCP). The frequency of rs508485TC genotype was significantly different in the studied groups (P = 0.0032; OR = 2.12; 95% CI, 1.29–3.48). In addition, the genotype frequencies showed a significant difference under dominant model ( P  = 0.005; OR = 2.79; 95% CI, 1.22–3.13). No mutation was detected in the Tudor domain of the  TDRD5  in the studied patients. In conclusion, we provide evidence for association between genetic variation in the  HIWI2  gene and idiopathic non-obstructive azoospermia in Iranian patients. Therefore, piRNA pathway genes variants can be considered as risk factors for male infertility.

Investigation of piwi-interacting RNA pathway genes role in idiopathic non-obstructive azoospermia