Evaluation of Ambient Ozone Pollution Exposure on Mice Testicular Tissue: An Integrated Metabolomic and Transcriptomic Analysis.

Abstract

The real ozone concentration in the air is rising yearly globally, which remarkably has adverse effect on human health, particularly on male fertility. Epidemiological studies showed that men exposure to ambient ozone was linked with decreased semen quality. Therefore, it is urgent to elucidate the toxicological evaluation of ozone exposure on men reproduction. This study conducted transcriptomic mRNA sequencing and high-performance liquid chromatography-tandem mass spectrometry to depict the characteristics of metabolomics and transcriptomics of mice testis tissue exposed to ozone. In transcriptomic, KEGG showed that spermatogenesis was significantly influenced by ozone exposure, meanwhile dysregulation of protein serine/threonine kinase activity, intracellular signal transduction, cell projection organization, and regulation of microtubule polymerization were observed, these molecular events participate in regulation and control of spermatogenesis. In metabolomic, twenty differential metabolites were the top abundance ranking features, as intermediate products of phospholipid metabolism to act as signal molecules, participating in intracellular signal transduction pathways, may affect the fluidity and structure of sperm cell membrane. Integrated omics showed that aminoacyl-tRNA biosynthesis was the main pathway attributed to significant correlation between transcriptomics and metabolomics (combination p value = 0.01), including arginine biosynthesis, essential for spermatogenesis. In integrated omics, several signatures were identified to be associated with spermatogenesis, including Creb3l4, Pgp and Tcp1, contributing to maturation of sperm head nuclei, energy metabolism and formation of sperm flagellum. The finding suggested ambient ozone exposure significantly altered the characteristics of transcriptome and metabolome of mice testis, and impaired spermatogenesis. Our finding provided new evidence of more stringent control and management for ambient ozone so as to reduce the potential risk of declined male fertility.