HSPH1 is essential for acrylamide-induced apoptosis and autophagy of mouse spermatogonial stem cells.

Acrylamide (ACR) is an organic compound widely used in daily life, and has been reported to cause damage to male reproductive system, while its role and mechanism in affecting the function of spermatogonial stem cells remains unknown. In this study, we showed that ACR induced apoptosis and autophagy of spermatogonial stem cell line (C18-4 cells), which was accompanied with upregulation of HSPH1. HSPH1 was subsequently shown to be involved in ACR-induced apoptosis and autophagy of C18-4 cells. In addition, Transcription factor Sp2 was identified to promote transcription of Hsph1 gene through binding to its gene promoter. Finally, Sp2/HSPH1 signaling pathway was proved to be involved in ACR-induced apoptosis and autophagy of C18-4 cells via inducing oxidative stress, and inhibition of autophagy significantly alleviated ACR-induced apoptosis. Taken together, our results demonstrate that ACR-triggered oxidative stress induces apoptosis and autophagy of mouse spermatogonial stem cells via activating Sp2/HSPH1 signaling pathway, and autophagy plays a cytotoxic role in ACR-induced apoptosis of the cells.