Bisphenol A induced apoptosis and transcriptome differences of spermatogonial stem cells in vitro

Bisphenol A (BPA) is widely used as an industrial plasticizer, which is also an endocrine disruptor and considered to have adverse effects on reproduction. In male mammals, the long-term production of billions of spermatozoa relies on the regulated proliferation and differentiation of spermatogonial stem cells (SSCs). However, little is known about the effects of BPA on the viability of SSCs. To investigate the influence of BPA exposure on SSCs in vitro, we isolated SSCs from mouse and successfully established in vitro propagation of SSCs. After BPA treatment, we found that BPA reduced the viability of SSCs and induced SSC apoptosis. For revealing the transcriptome differences of the BPA-treated SSCs, we performed high-throughput RNA sequencing and found that 860 genes were differentially expressed among 18,272 observed genes. The gene ontology (GO) terms, regulation of programmed cell death and apoptotic process, were enriched in the differentially expressed genes (DEGs). Among the cluster of DEGs associated with the kyoto encyclopedia of genes and genomes (KEGG) apoptosis pathway, activating transcription factor 4 (Atf4) and DNA damage inducible transcript 3 (Ddit3) genes were significantly up-regulated in BPA-treated SSCs, which were proved by qPCR. Taken together, these findings suggest that BPA can increase the mRNA expression of pro-apoptosis genes and reduce the viability of SSCs by inducing apoptosis.