Expression profile of circular RNAs in continuous light-induced ovarian dysfunction

Purpose: This study aims to elucidate the underlying relationship between the expression profiles of circular RNAs (circRNAs) and the ovarian dysfunction induced by continuous light. Methods: High-throughput sequencing was used to profile the transcriptome of differentially expressed circRNAs (DEcircRNAs) in rat ovary under continuous light exposure (12 h:12 h light/light cycle, L/L group) and a control cycle (12 h:12 h light/dark cycle, L/D group). Gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and circRNAs-microRNAs-messenger RNAs networks were performed to predict the role of DEcircRNAs in biological processes and pathways. A quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) assay was conducted to verify the high-throughput sequencing results and the expression level of circadian rhythm genes. Results: In total, 305 circRNAs were differentially expressed between the L/L and L/D groups. Among these, 211 circRNAs were up regulated, while 94 were down regulated. Eight candidate circRNAs from 305 DEcircRNAs were verified by qRT‐PCR. Further bioinformatics analysis revealed that interactions between DEcircRNAs and a set of microRNAs involved in ovarian dysfunction-related pathways, such as regulation of androgen receptors, gonadotrophin releasing hormone signaling pathway, endocrine resistance, etc. Subsequently, we identified rno_circ:chr2:86868285-86964272 and rno_circ:chr1:62330221-62360073 may participate in the pathophysiology of ovarian dysfunction by constructing circRNAs-microRNAs-messenger RNAs networks. Meanwhile, constant light reduced the expression of circadian rhythm genes CLOCK, BAML1, PER1, and PER2 compared with that of controls. Caspase3 and Bax were up regulated in the L/L group compared with the L/D group, while Bcl-2 was down regulated. Conclusions: In summary, the results reveal that the expression profiles and potential functions of DEcircRNAs in rat ovaries may play important roles in continuous light-induced ovarian dysfunction. These findings provide novel clues and molecular targets for studying the mechanisms and clinical therapy of ovarian dysfunction.