Abstract
Non-obstructive azoospermia is a severe infertility factor. Currently, the etiology of this condition remains elusive with several possible molecular pathway disruptions identified in the post-meiotic spermatozoa. In the presented study, in order to identify all possible candidate genes associated with azoospermia and to map their relationship, we present the first protein-protein interaction network related to azoospermia and analyze the complex effects of the related genes systematically. Using Online Mendelian Inheritance in Man, the Human Protein Reference Database and Cytoscape, we created a novel network consisting of 209 protein nodes and 737 interactions. Mathematical analysis identified three proteins, ar, dazap2, and esr1, as hub nodes and a bottleneck protein within the network. We also identified new candidate genes, CREBBP and BCAR1, which may play a role in azoospermia. The gene ontology analysis suggests a genetic link between azoospermia and liver disease. The KEGG analysis also showed 45 statistically important pathways with 31 proteins associated with colorectal, pancreatic, chronic myeloid leukemia and prostate cancer. Two new genes and associated diseases are promising for further experimental validation.
Highlights
Male factor infertility is involved in over 50% of couples trying to conceive [1]
Construction and Parameters of Protein-Protein study, construction and analysis of a protein-protein interaction network were applied in order extensively consider all the cell functions of the proteins associated with the azoospermia and the
The retrieved data were entered into Cytoscape 2.8 to construct the Protein-Protein Interaction (PPI) network
Summary
Male factor infertility is involved in over 50% of couples trying to conceive [1]. The increasing role of the male factor in cases of couples’ infertility has been identified due to the increased evaluation of male reproductive function and the development of new diagnostic tools [2,3]. Non-obstructive azoospermia (NOA) is considered to be a severe male infertility factor due to the impaired spermatogenesis with the consequent absence of spermatozoa in the ejaculate [5]. Intracytoplasmic sperm injection (ICSI) as an assisted reproductive technology is an efficient therapy for severe male infertility, the success rate for NOA cases following ICSI therapy is around 36% [6]. Previous research has studied the medical treatment to improve the sperm quality of the patients before carrying out ICSI cycles [7]. While understanding the overall mechanism of azoospermia is very important to improve the medical therapy, the underlying etiology and mechanism(s) remain elusive [4,7]
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