Small Non-coding RNAs and Male Infertility

Male germ cells carry a complex RNA payload, whose quantity and composition varies during the different stages of spermatogenesis. Small non-coding RNA comprise microRNAs (miRNA), piwi-interacting RNAs (piRNA), tRNA derived small RNAs (tsRNA), endogenous siRNAs, and rRNA-derived small RNAs. MicroRNAs regulate the self-renewal and differentiation of spermatogonial stem cells, as well as their progression through meiosis, while piRNA are thought to play a crucial role at pachytene stage of adult spermatogenesis, since defective piRNA processing has been found in azoospermic men with spermatogenesis arrested mainly at late pachytene spermatocytes, and in preimplantation embryo during epigenetic reprogramming events, when they regulate de novo methylation and repress transposable elements expression. During the transit through the epididymis, sperm acquire a number of miRNA whose composition vary in the caput, corpus, and cauda, which play a fundamental role in embryo development. TsRNA are also acquired in the epididymis, and are involved in sperm maturation, fertilization, and embryonic development. Small noncoding RNA are also responsible for intergenerational and transgenerational epigenetic inheritance of environmental experiences and metabolic disorders and are currently evaluated in the infertile men as diagnostic and prognostic tools, particularly in case of azoospermia due to spermatogenic dysfunction and unexplained infertility in men with normozoospermia.