Nanjing University of Chinese Medicine, Nanjing 210029, China; Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
Nanjing University of Chinese Medicine, Nanjing 210029, China; Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
Ecotoxicol Environ Saf. 2022 Sep 1;242:113861. doi: 10.1016/j.ecoenv.2022.113861. Epub 2022 Jul 11.
This study aims to elucidate the underlying relationship between the expression profiles of circular RNAs (circRNAs) and the ovarian dysfunction induced by continuous light.
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.
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.
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.
本研究旨在阐明环状 RNA（circRNA）表达谱与持续光照诱导的卵巢功能障碍之间的潜在关系。
采用高通量测序技术分析持续光照（12 h：12 h 光照/光照周期，L/L 组）和对照周期（12 h：12 h 光照/黑暗周期，L/D 组）下大鼠卵巢中差异表达的 circRNAs（DEcircRNAs）的转录组。进行基因本体（GO）富集分析、京都基因与基因组百科全书（KEGG）通路分析和 circRNAs-微小 RNA-信使 RNA 网络，以预测 DEcircRNAs 在生物学过程和通路中的作用。采用实时定量逆转录聚合酶链反应（qRT-PCR）检测验证高通量测序结果和昼夜节律基因的表达水平。
总共在 L/L 和 L/D 组之间有 305 个 circRNAs 差异表达。其中，211 个 circRNAs 上调，94 个下调。从 305 个 DEcircRNAs 中选择 8 个候选 circRNAs 通过 qRT-PCR 进行验证。进一步的生物信息学分析表明，DEcircRNAs 与一组参与卵巢功能障碍相关途径的 microRNAs 之间存在相互作用，如雄激素受体调节、促性腺激素释放激素信号通路、内分泌抵抗等。随后，我们鉴定出 rno_circ：chr2：86868285-86964272 和 rno_circ：chr1：62330221-62360073 通过构建 circRNAs-微小 RNA-信使 RNA 网络可能参与卵巢功能障碍的病理生理学。同时，与对照组相比，持续光照降低了 CLOCK、BAML1、PER1 和 PER2 等昼夜节律基因的表达。与 L/D 组相比，L/L 组中的 Caspase3 和 Bax 上调，而 Bcl-2 下调。
综上所述，该研究结果表明，大鼠卵巢中 DEcircRNAs 的表达谱和潜在功能可能在持续光照诱导的卵巢功能障碍中发挥重要作用。这些发现为研究卵巢功能障碍的机制和临床治疗提供了新的线索和分子靶点。
