Department of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, 210004, China.
Mol Biol Rep. 2023 Oct;50(10):8081-8088. doi: 10.1007/s11033-023-08705-w. Epub 2023 Aug 4.
Advanced paternal age (APA) is associated with decreased fertility, but the mechanism underlying APA remains unknown. CircRNAs have been reported to be ideal candidate biomarkers for diagnostic and therapeutic applications in many diseases and are also involved in spermatogenesis. Hence, we aimed to assess the circRNA expression profile of spermatozoa from aging men.
We recruited 6 subjects, including 3 in the younger group (men age < 40) and 3 in the APA group (men age ≥ 40). RNA sequencing was exploited to identify the expression profiles of circRNAs between the two groups. The expression levels of circRNAs were validated using real-time quantitative polymerase chain reaction (RT-qPCR). Kyoto Encyclopedia of Genes and Genomes biological pathway analysis and Gene Ontology analysis were performed to evaluate the functions of differentially expressed circRNAs (DE-circRNAs) between the two groups. In total, 18,787 circRNAs were sequenced in the spermatozoa of two groups. Our analysis revealed that there were 1056 downregulated circRNAs and 1228 upregulated circRNAs between the two groups, and KEGG analysis showed they were mainly involved in pathways including the DNA repair signaling pathway, meiotic recombination signaling pathway, and PI3K/AKT signaling pathway.
In conclusion, our study suggested that circRNAs play a vital role in spermatozoa from aging men and provided a fresh perspective on the specific regulatory mechanism of spermatozoa from aging men.
高龄父亲（Advanced Paternal Age，APA）与生育能力下降有关，但 APA 的潜在机制尚不清楚。CircRNAs 已被报道为许多疾病的诊断和治疗应用的理想候选生物标志物，并且也参与精子发生。因此，我们旨在评估来自衰老男性精子的 circRNA 表达谱。
我们招募了 6 名受试者，包括 3 名年龄较小的组（男性年龄<40 岁）和 3 名 APA 组（男性年龄≥40 岁）。利用 RNA 测序来鉴定两组之间 circRNA 的表达谱。使用实时定量聚合酶链反应（RT-qPCR）验证 circRNA 的表达水平。京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）生物途径分析和基因本体论（Gene Ontology，GO）分析用于评估两组之间差异表达的 circRNA（DE-circRNA）的功能。总共对两组精子中的 18787 个 circRNA 进行了测序。我们的分析表明，两组之间有 1056 个下调的 circRNA 和 1228 个上调的 circRNA，KEGG 分析表明它们主要涉及 DNA 修复信号通路、减数分裂重组信号通路和 PI3K/AKT 信号通路等途径。
总之，我们的研究表明 circRNA 在衰老男性的精子中发挥着重要作用，并为衰老男性精子的特定调节机制提供了新的视角。
