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A transcriptomic regulatory network among miRNAs, piRNAs, circRNAs, lncRNAs and mRNAs regulates microcystin-leucine arginine (MC-LR)-induced male reproductive toxicity. 2019

Xiannan Meng, and Haoran Peng, and Yuanzhen Ding, and Ling Zhang, and Jingping Yang, and Xiaodong Han
Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093, China.

Microcystin-leucine arginine (MC-LR) which is produced by cyanobacteria is a potent toxin for the reproductive system. Our previous work has demonstrated that both acute and chronic reproductive toxicity engendered by MC-LR can result in the decline of sperm quality and damage of testicular structures in male mice. The present study was designed to investigate the impact of chronic low-dose exposure to MC-LR on the regulation of RNA networks including mRNA, microRNA (miRNA), piwi-associated RNA (piRNA), covalently closed circular RNA (circRNA) and long non-coding RNA (lncRNA) in testicular tissues. By high-throughput sequencing analysis, 1091 mRNAs, 21 miRNAs, 644 piRNAs, 278 circRNAs and 324 lncRNAs were identified to be significantly altered in testicular tissues treated with MC-LR. We performed gene ontology (GO) analysis to ascertain the biological functions of differentially expressed genes. Among the altered 21 miRNAs and 644 piRNAs, the miRNA chr13_8977, which is a newly discovered species, and the piRNA mmu_piR_027558 were dramatically down-regulated after exposure to MC-LR. Consistently, both mRNA levels and protein expression levels of their predicted targets were increased significantly when chr13_8977 and mmu_piR_027558 were each down-regulated. Testicular structures, germ cell apoptosis and sperm quality were also affected by the altered expression of chr13_8977 and mmu_piR_027558 severally. We further investigated the differential expression of circRNAs and lncRNAs and their biological functions in testicular tissues following treatment with chronic low-dose exposure to MC-LR. We also constructed a competing endogenous RNA (ceRNA) network to predict the functions of the altered expressed RNAs using MiRanda. Our study suggested a crucial role for the potential network regulation of miRNAs, piRNAs, circRNAs, lncRNAs and mRNAs impacting the cytotoxicity of MC-LR in testicular tissues, which provides new perspectives in the development of diagnosis and treatment strategies for MC-LR-induced male reproductive toxicity.

UI MeSH Term Description Entries
D007930 Leucine An essential branched-chain amino acid important for hemoglobin formation. L-Leucine,Leucine, L-Isomer,L-Isomer Leucine,Leucine, L Isomer
D008297 Male Males
D012098 Reproduction The total process by which organisms produce offspring. (Stedman, 25th ed) Human Reproductive Index,Human Reproductive Indexes,Reproductive Period,Human Reproductive Indices,Index, Human Reproductive,Indexes, Human Reproductive,Indices, Human Reproductive,Period, Reproductive,Periods, Reproductive,Reproductive Index, Human,Reproductive Indices, Human,Reproductive Periods
D000079962 RNA, Circular RNA molecules in which the 3' and 5' ends are covalently joined to form a closed continuous loop. They are resistant to digestion by EXORIBONUCLEASES. Circular Intronic RNA,Circular RNA,Circular RNAs,Closed Circular RNA,ciRNA,circRNA,circRNAs,Circular RNA, Closed,Intronic RNA, Circular,RNA, Circular Intronic,RNA, Closed Circular,RNAs, Circular
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001120 Arginine An essential amino acid that is physiologically active in the L-form. Arginine Hydrochloride,Arginine, L-Isomer,DL-Arginine Acetate, Monohydrate,L-Arginine,Arginine, L Isomer,DL Arginine Acetate, Monohydrate,Hydrochloride, Arginine,L Arginine,L-Isomer Arginine,Monohydrate DL-Arginine Acetate
D012313 RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) RNA, Non-Polyadenylated,Ribonucleic Acid,Gene Products, RNA,Non-Polyadenylated RNA,Acid, Ribonucleic,Non Polyadenylated RNA,RNA Gene Products,RNA, Non Polyadenylated
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D013737 Testis The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS. Testicles,Testes,Testicle
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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