Open Access Research article

Testis transcriptome analysis in male infertility: new insight on the pathogenesis of oligo-azoospermia in cases with and without AZFc microdeletion

Valentina Gatta12, Florina Raicu34, Alberto Ferlin5, Ivana Antonucci12, Anna Paola Scioletti24, Andrea Garolla5, Giandomenico Palka16, Carlo Foresta5 and Liborio Stuppia127*

  • * Corresponding author: Liborio Stuppia

  • † Equal contributors

Author Affiliations

1 Department of Biomedical Sciences, "G. d'Annunzio" University, Chieti-Pescara, Italy

2 Aging Center Research, "G. d'Annunzio" Foundation, Chieti-Pescara, Italy

3 Carol Davila University of Medicine and Pharmacy, Genetics Chair, Bucharest, Romania

4 Department of Clinical Sciences and Imaging, "G. d'Annunzio" University, Chieti-Pescara, Italy

5 Centre for Male Gamete Cryopreservation, Department of Histology, Microbiology, and Medical Biotechnologies, University of Padova, Italy

6 Human Genetics Division, "Spirito Santo" Hospital, Pescara, Italy

7 IGM-CNR c/o IOR, Bologna, Italy

For all author emails, please log on.

BMC Genomics 2010, 11:401  doi:10.1186/1471-2164-11-401

Published: 24 June 2010



About 10% of cases of male infertility are due to the presence of microdeletions within the long arm of the Y chromosome (Yq). Despite the large literature covering this critical issue, very little is known about the pathogenic mechanism leading to spermatogenesis disruption in patients carrying these microdeletions. In order to identify the presence of specific molecular pathways leading to spermatogenic damage, testicular gene expression profiling was carried out by employing a microarray assay in 16 patients carrying an AZFc microdeletion or affected by idiopathic infertility. Hierarchical clustering was performed pooling the data set from 26 experiments (16 patients, 10 replicates).


An intriguing and unexpected finding is that all the samples showing the AZFc deletion cluster together irrespectively of their testicular phenotypes. This cluster, including also four patients affected by idiopathic infertility, showed a downregulation of several genes related to spermatogenesis that are mainly involved in testicular mRNA storage. Interestingly, the four idiopathic patients present in the cluster showed no testicular expression of DAZ despite the absence of AZFc deletion in the peripheral blood.


Our expression profiles analysis indicates that several forms of infertility can be triggered by a common pathogenic mechanism that is likely related to alterations in testicular mRNA storage. Our data suggest that a lack of testicular DAZ gene expression may be the trigger of such mechanism. Furthermore, the presence of AZFc deletions in mosaic or the loss of function of AZFc genes in absence of Yq deletion can perhaps explain these findings. Finally, based on our data, it is intriguing to hypothesize that DAZ gene dysfunctions can account for a larger number of previously thought "idiopathic" infertility cases and investigation of such testicular gene dysfunction can be important to reveal the molecular determinant of infertility than are undetected when only testing Yq deletions in peripheral blood.