Transcriptome profiling and pathway analysis of the effects of mono‑(2‑ethylhexyl) phthalate in mouse Sertoli cells

Abstract

Phthalates are confirmed to have toxic effects on the reproductive system and are likely to have further damaging actions in humans. The present study explored the molecular mechanisms of the toxic effect of mono-(2-ethylhexyl) phthalate (MEHP) on mouse Sertoli cells. Cell apoptosis and proliferation assays were used to assess the effects of MEHP on the TM4 Sertoli cell line derived from mouse testes. TM4 cells were treated with two doses of MEHP or left untreated as a control group, followed by RNA extraction and analysis using high-throughput transcriptome sequencing technology. The gene expression profile obtained was then subjected to a bioinformatics analysis to explore the molecular mechanisms of reproductive toxicity. The results revealed that 528 and 269 genes were upregulated in the high- and low-dose MEHP groups of cells compared with the control group, while 148 and 173 genes were downregulated. Gene ontology (GO) analysis indicated that the differently expressed genes were associated with the GO term 'extracellular region' of the cellular component domain in the high and low MEHP groups. Compared with the control group, eight common pathway changes were identified in the high- and low-dose MEHP groups, including 'terpenoid backbone biosynthesis'. Reverse transcription-quantitative polymerase chain reaction analysis was used to validation, and hermetic effects were observed for certain genes. These results provide an important basis and experimental data for further research into the mechanisms of phthalate-induced toxicity.