Identification of candidate causal genes and their associated pathogenic mechanisms underlying teratozoospermia based on the spermatozoa transcript profiles.

Teratozoospermia with unclear pathomechanism is one of the common causes for failed fertilisation. This study aimed to further explore the pathological mechanism for teratozoospermia. Spermatozoal transcript profiles generated from 13 normal fertile men and eight infertile males with a consistent severe heterogeneous teratozoospermia were used. These data were pre-processed, and differentially expressed genes were screened. Besides, gene ontology and pathway enrichment analysis were performed, and then, protein-protein interaction (PPI) network was constructed, and spermatogenesis-related genes in the PPI network were extracted. As a result, 366 up-regulated and 2158 down-regulated genes were identified. Multiple gene ontology terms and pathways including cell-cell signalling and reproduction enriched by differentially expressed genes were obtained. Moreover, four clusters including cluster 1 associated with RNA catabolic process were identified from the PPI network. In addition, genes including cyclin B1, proteasome (prosome, macropain) activator subunit 4, Rac GTPase-activating protein 1 and pituitary tumour-transforming 1 were received. In conclusion, abnormal expression of cyclin B1 and Rac GTPase-activating protein 1, still proteasome (prosome, macropain) activator subunit 4 and pituitary tumour-transforming 1 would impede cell cycle progression during sperm development and maturation, which may contribute to the occurrence and development of teratozoospermia.