Abstract
Background/Objectives: Primary, idiopathic, impaired spermatogenesis (IS) affects approximately 2% of men and can manifest as oligozoospermia or azoospermia. Methods: In order to gain insights into the genetic mechanisms involved, a systematic analysis of historical microarray data from testes with IS was conducted by first constructing a global map of signalling networks involving genes differentially expressed between IS and control testes (CT). The centrally located genes and their interacting genes were then extracted to create a sub-network representing the pathways active in IS. Results: Two routes to germ cell death or cycle arrest were revealed: either via receptor tyrosine kinases or integrin β (ITGB) genes; the latter being a novel finding. Another analysis, using leave-one-out machine-learning validation, was performed and also showed that ITGB expression distinguished IS from CT. Computational simulation confirmed the ITGB protein family regulates a majority of the other proteins in its pathway whether the expression level was reduced or increased, indicating ITGB could be a key protein in IS. Conclusions: These computational analyses identify ITGB, particularly ITGB1, as a potential molecular marker associated with idiopathic impaired spermatogenesis and provide insights into signalling mechanisms underlying the condition.