Background: Triptolide has been shown to exert various pharmacological effects on systemic autoimmune
diseases and cancers. However, its severe toxicity, especially reproductive toxicity, prevents its widespread
clinical use for people with fertility needs. Noncoding RNAs including lncRNAs and circRNAs are novel regulatory
molecules that mediate a wide variety of physiological activities; they are crucial for spermatogenesis and their dysregulation
might cause male infertility. However, whether they are involved in triptolide-induced reproductive toxicity
is completely unknown.
Methods: After exposure of mice to triptolide, the total RNAs were used to investigate lncRNA/circRNA/mRNA
expression profiles by strand-specific RNA sequencing at the transcriptome level to help uncover RNA-related
mechanisms in triptolide-induced toxicity.
Results: Triptolide significantly decreased testicular weight, damaged testis and sperm morphology, and reduced
sperm motility and density. Remarkable deformities in sperm head and tail were also found in triptolide-exposed
mice. At the transcriptome level, the triptolide-treated mice exhibited aberrant expression profiles of
lncRNAs/circRNAs/mRNAs. Gene Ontology and pathway analyses revealed that the functions of the differentially
expressed lncRNA targets, circRNA cognate genes, and mRNAs were closely linked to many processes involved in
spermatogenesis. In addition, some lncRNAs/circRNAs were greatly upregulated or inducibly expressed, implying
their potential value as candidate markers for triptolide-induced male reproductive toxicity.
Conclusion: This study provides a preliminary database of triptolide-induced transcriptome, promotes understanding
of the reproductive toxicity of triptolide, and highlights the need for research on increasing the medical efficacy of
triptolide and decreasing its toxicity.