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Micro RNA expression profiles in testicular biopsies of patients with impaired spermatogenesis
Author(s) -
Noveski P.,
PopovskaJankovic K.,
KubelkaSabit K.,
Filipovski V.,
Lazarevski S.,
Plaseski T.,
PlaseskaKaranfilska D.
Publication year - 2016
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12246
Subject(s) - microrna , spermatogenesis , biology , gene , sertoli cell , microarray analysis techniques , gene expression , azoospermia , andrology , messenger rna , regulation of gene expression , apoptosis , microarray , microbiology and biotechnology , genetics , endocrinology , medicine , infertility , pregnancy
Summary Spermatogenesis is a complex process that involves thousands of genes whose expression during different stages is strictly regulated. Small non‐coding micro RNA s play an important role in the posttranscriptional regulation of mRNA processing during spermatogenesis. Using Agilent SurePrint v16 micro RNA 8 × 60 K microarray kit, we investigated the micro RNA expression profiles of 24 formalin‐fixed paraffin‐embedded testicular biopsies from patients with hypospermatogenesis ( n = 10), hypospermatogenesis and azoospermia factor c region on the Y chromosome (AZFc) deletion ( n = 3), Sertoli cell‐only syndrome ( n = 3) and maturation arrest ( n = 2), in comparison with subjects with normal spermatogenesis ( n = 6). After adjusting for multiple testing, six deregulated mi RNA s were detected in the patients with AZF c deletion, 30 in maturation arrest group, 52 in Sertoli cell‐only syndrome group of patients, and none in the group of patients with hypospermatogenesis. Some of the deregulated micro RNA s were shared between groups, resulting in 58 unique differentially expressed micro RNA s. The expression of five micro RNA s (hsa‐miR‐34b, hsa‐miR‐449b, hsa‐miR‐517c, hsa‐miR‐181c, and hsa‐miR‐605) was validated by qRT ‐ PCR in a total of 74 samples. Using mRNA expression profiles of subjects with matching histopathological patterns of impaired spermatogenesis from publically available Gene Expression Omnibus data sets, we have performed integrated mRNA –micro RNA regulatory network analysis. Pathway analysis revealed significantly enriched set of genes for tumor necrosis factor‐related apoptosis‐inducing ligand signaling pathway, previously shown to be involved in regulation of apoptosis in normal functioning testis. Our results should be considered as preliminary as we have analyzed only a small number of patients in each studied group. Further studies with larger number of patients with impaired spermatogenesis as well as more targeted approaches with parallel micro RNA and mRNA expression profiling in isolated subpopulations of somatic or germ cells from different stages of spermatogenesis are needed to clarify the role of the micro RNA s in the process of spermatogenesis.