RNA-Seq Analysis of Testes from Mice Exposed to Neodymium Oxide

Abstract

(1) Objective: Rare earth neodymium oxide (Nd2O3) is refined and used extensively around the world, and the occupational and environmental safety of rare piles of the earth has attracted considerable attention. Nd2O3 enters the human body through the respiratory system, reaches various organs through blood circulation, and accumulates to produce toxic effects. At present, little is known about the reproductive toxicity of Nd2O3. Non-coding RNAs participate in a variety of physiological activities and are very important for spermatogenesis. However, it is unknown whether they are involved in Nd2O3-induced reproductive toxicity. Therefore, we conducted a pathological analysis, sperm quality testing, and RNA-seq on the testicular tissue of mice exposed to Nd2O3 to find the key genes and regulatory pathways of male reproductive damage and explore the early biomarkers and mechanisms of reproductive damage caused by Nd2O3. (2) Methods: After exposure of mice to Nd2O3, we carried out a pathological analysis and RNA-seq analysis for miRNAs/lncRNAs/circRNAs/mRNAs on the testicular tissue of mice, and the total RNAs were used to investigate miRNA/lncRNA/circRNA/mRNA expression profiles by strand-specific RNA sequencing at the transcriptome level to help uncover RNA-related mechanisms in Nd2O3-induced toxicity. (3) Results: Nd2O3 damaged testis and sperm morphology, significantly decreased the number of sperm, and deformed the sperm head and tail. RNA-seq analysis showed that the expression level of mRNA/miRNA/circRNA/lncRNA in the testicular tissue of mice exposed to Nd2O3 is abnormal. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the functional enrichment of differentially expressed genes (DEGs) and their target genes was closely related to the related pathway of spermatogenesis. Furthermore, some miRNAs/lncRNAs/circRNAs that were greatly upregulated or inducibly expressed, implying their potential value as candidate markers for Nd2O3-induced reproductive toxicity, help us to further investigate the mechanisms of key genes, key signaling pathways, and inter-gene regulation for Nd2O3-induced reproductive toxicity. (4) Conclusions: This study provides the first database of a Nd2O3-induced transcriptome. This information is useful for the development of biomarkers of Nd2O3-induced reproductive injury and promotes understanding of the reproductive toxicity mechanism of Nd2O3.

Toxic Effects of Rare Earth Elements on Human Health: A Review

“…Secondly, with the intensive study of epigenetics in disease development, research into non-coding RNA (ncRNA) as a molecular target has become a hot topic. High-throughput sequencing results showed that REE-induced damage was related to abnormal changes in ncRNA expression profiles [102]. For example, in a human bronchial epithelial cell model exposed to nanoparticles of neodymium oxide (NPs-Nd 2 O 3 ), 1915 circRNAs (1025 up-regulated and 890 down-regulated) were abnormally expressed, inducing tissue dysfunction through sponge miRNAs [103].…”