Feng Xiaoqin, Luo Jinhong
Department of Reproductive Medicine, Shanxi Provincial People's Hospital, Taiyuan, 030012, Shanxi, China.
Shanxi Ecological Environment Monitoring and Emergency Response Centre, Shanxi Academy of Eco-Environmental Sciences, Taiyuan, 030024, Shanxi, China.
Reprod Sci. 2025 Jun 23. doi: 10.1007/s43032-025-01907-6.
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.
全球空气中实际的臭氧浓度逐年上升，这对人类健康，尤其是男性生育能力，有着显著的不利影响。流行病学研究表明，男性暴露于环境臭氧中与精液质量下降有关。因此，阐明臭氧暴露对男性生殖的毒理学评估迫在眉睫。本研究进行了转录组mRNA测序和高效液相色谱-串联质谱分析，以描绘暴露于臭氧的小鼠睾丸组织的代谢组学和转录组学特征。在转录组学方面，KEGG显示精子发生受到臭氧暴露的显著影响，同时观察到蛋白质丝氨酸/苏氨酸激酶活性、细胞内信号转导、细胞突起组织和微管聚合调节的失调，这些分子事件参与精子发生的调控。在代谢组学方面，20种差异代谢物是丰度排名靠前的特征，作为磷脂代谢的中间产物充当信号分子，参与细胞内信号转导途径，可能影响精子细胞膜的流动性和结构。综合组学显示，氨酰-tRNA生物合成是转录组学和代谢组学之间显著相关的主要途径（联合p值 = 0.01），包括对精子发生至关重要的精氨酸生物合成。在综合组学中，鉴定出几个与精子发生相关的特征，包括Creb3l4、Pgp和Tcp1，它们有助于精子头部细胞核的成熟、能量代谢和精子鞭毛的形成。该发现表明，环境臭氧暴露显著改变了小鼠睾丸的转录组和代谢组特征，并损害了精子发生。我们的发现为更严格地控制和管理环境臭氧提供了新证据，以降低男性生育能力下降的潜在风险。
