Abstract
Currently, the molecular mechanisms underlining male infertility are still poorly understood. Our previous study has demonstrated that PIWI-interacting RNAs (piRNAs) are downregulated in seminal plasma of infertile patients and can serve as molecular biomarkers for male infertility. However, the source and mechanism for the dysregulation of piRNAs remain obscure. In this study, we found that exosomes are present in high concentrations in human seminal plasma and confirmed that piRNAs are predominantly present in the exosomal fraction of seminal plasma. Moreover, we showed that piRNAs were significantly decreased in exosomes of asthenozoospermia patients compared with normozoospermic men. By systematically screening piRNA profiles in sperms of normozoospermic men and asthenozoospermia patients, we found that piRNAs were parallelly reduced during infertility. At last, we investigated the expression of some proteins that are essential for piRNAs biogenesis in sperms and therefore identified a tight correlation between the levels of spermatozoa piRNA and MitoPLD protein, suggesting that the loss-of-function of MitoPLD could cause a severe defect of piRNA accumulation in sperms. In summary, this study identified a parallel reduction of piRNAs and MitoPLD protein in sperms of asthenozoospermia patients, which may provide pathophysiological clues about sperm motility.
Highlights
Infertility is a prevalent health problem and affects nearly 15% of couples all over the world [1, 2]
What is becoming clear is that PIWI-interacting RNAs (piRNAs) are participate in posttranscriptional regulation of protein-coding genes as well piRNAs and MitoPLD Are Reduced
MitoPLD, a mitochondriaanchored endonuclease belonging to the member of the phospholipase D superfamily proteins, is conserved among diverse species and is implicated in the primary processing pathway of piRNAs
Summary
Infertility is a prevalent health problem and affects nearly 15% of couples all over the world [1, 2]. PiRNAs are approximately 26-31 nucleotides in length and expressed mainly in pachytene spermatocytes and round spermatids in the testis of mammals [6,7,8,9]. They are named PIWIinteracting RNAs because of their close relationship with the PIWI subfamily members. The pathway about primary piRNAs generation is not well studied, but a mitochondrial protein, MitoPLD ( known as Zucchini or PLD6), a member of the nuclease/phospholipase D family, has been proposed to function as an endonuclease to generate the 5’ ends of piRNAs [13,14,15]. Because of the diverse and pivotal roles of piRNAs in the male reproductive system, the dysregulation and dysfunction of piRNA often cause male infertility
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