Altered miRNA Signature of Developing Germ-cells in Infertile Patients Relates to the Severity of Spermatogenic Failure and Persists in Spermatozoa
Muñoz Miralles, Xavier (Institut d'Investigació Biomèdica de Bellvitge)
Mata, Ana (Fundació Puigvert)
Bassas, Lluís (Institut d'Investigació Biomèdica Sant Pau)
Larriba, Sara (Institut d'Investigació Biomèdica de Bellvitge)
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2015
Resum:	The aim of this study was to assess the cellular miRNA expression behaviour in testes with spermatogenic failure (SpF). We performed a high-throughput screen of 623 mature miRNAs by a quantitative RT-qPCR-based approach in histologically well-defined testicular samples with spermatogenic disruption at different germ-cell stages, which revealed altered patterns of miRNA expression. We focussed on the differentially expressed miRNAs whose expression correlated with the number of testicular mature germ-cells and described the combined expression values of a panel of three miRNAs (miR-449a, miR-34c-5p and miR-122) as a predictive test for the presence of mature germ-cells in testicular biopsy. Additionally, we determined decreased cellular miRNA content in developing germ-cells of SpF testis; this was more noticeable the earlier the stage of germ-cell differentiation was affected by maturation failure. Furthermore, we showed that the miRNA expression profile in mature sperm from mild SpF patients was widely altered. Our results suggest that the cellular miRNA content of developed germ-cells depends heavily on the efficacy of the spermatogenic process. What is more, spermatozoa that have fulfilled the differentiation process still retain the dysregulated miRNA pattern observed in the developing SpF germ-cells. This altered miRNA molecular signature may have functional implications for the male gamete.
Ajuts:	Generalitat de Catalunya 2009SGR01490 Generalitat de Catalunya 2014SGR541 Ministerio de Economía y Competitividad PI12/00361
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Adult ; Cell Differentiation ; Gene Expression ; Gene Expression Profiling ; Germ Cells ; Humans ; Infertility, Male ; Male ; MicroRNAs ; Middle Aged ; Phenotype ; Spermatogenesis ; Spermatozoa ; Testis ; Transcriptome
Publicat a:	Scientific reports, Vol. 5 (september 2015) , p. 17991, ISSN 2045-2322

DOI: 10.1038/srep17991
PMID: 26648257

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