AUTHOR=Manfrevola Francesco , Chioccarelli Teresa , Cobellis Gilda , Fasano Silvia , Ferraro Bruno , Sellitto Carolina , Marella Giovanni , Pierantoni Riccardo , Chianese Rosanna 

TITLE=CircRNA Role and circRNA-Dependent Network (ceRNET) in Asthenozoospermia

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00395

DOI=10.3389/fendo.2020.00395

ISSN=1664-2392

ABSTRACT=CircRNA role in reproduction is under investigation. CircRNAs are expressed in human testis, spermatozoa (SPZ) and seminal plasma. Their involvement in embryo development has also been suggested.
Asthenozoospermia, a common cause of male infertility, is characterized by reduced or absent sperm motility in fresh ejaculate. While abnormal mitochondrial function, altered sperm tail and genomic causes have been deeply investigated, the epigenetic signature of asthenozoospermic derived SPZ still remains unexplored. CircRNAs may take part to the repertoire of differentially expressed molecules in infertile men. Starting from this background, we carried out a circRNA microarray identifying a total of 9138 transcripts, 22% of them novel based and 83.5% with exonic structure. By using KEGG analysis, we evaluated circRNA contribution in pathways related to mitochondrial function and sperm motility. In order to discriminate circRNAs with a differential expression in SPZ with differential morphological parameters, we separated sperm cells by Percoll gradient and analyzed their differential circRNA payload. Bioinformatic approach was, then, utilized to build a circRNA/miRNA/mRNA network. With the aim to demonstrate a dynamic contribution of circRNAs to the sperm epigenetic signature, we verified their modulation as a consequence of an oral amino acid supplementation, efficacious in improving SPZ motility.