Cry1 deficiency leads to testicular dysfunction and altered expression of genes involved in cell communication, chromatin reorganization, spermatogenesis, and immune response in mouse testis.

Cryptochrome (Cry)1 is essential for generating circadian rhythm in central and many peripheral oscillators; however, its role in male reproduction remains unclear. We investigated this question using Cry1 knockout (KO) mice. We found that Cry1 is necessary for normal testicular function: Cry1 deficiency increased testicular germ cell apoptosis and decreased sperm count. A transcriptome analysis showed that the expression levels of 375 genes-including 12 encoding micro (mi)RNAs-were altered in the testis of Cry1 KO mice relative to wild-type controls. A bioinformatics analysis revealed that the differentially expressed genes were related to important biological processes including cell-cell communication, metabolism, chromatin reorganization, spermatogenesis, and the immune response. An integrative analysis of miRNA-mRNA networks suggested that the 12 dysregulated miRNAs may contribute to testis disorders through negative regulation of their target mRNAs expression in testis, and interestingly, all the 12 miRNAs are predicted to target core circadian clock components. These results provide the first evidence of a correlation between dysregulation of Cry1 and male reproductive defects in mice, indicating that Cry1 plays a critical role in maintaining normal testicular function.