高脂饮食小鼠精子和附睾中循环RNA故事的新视角。
Novel Insights into circRNA Saga Coming from Spermatozoa and Epididymis of HFD Mice.
发表日期:2023 Apr 06
作者:
Francesco Manfrevola, Teresa Chioccarelli, Vincenza Grazia Mele, Veronica Porreca, Monica Mattia, Donatella Cimini, Antonella D'Agostino, Gilda Cobellis, Silvia Fasano, Chiara Schiraldi, Rosanna Chianese, Riccardo Pierantoni
来源:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
摘要:
肥胖症是一种病理生理紊乱,与脂肪堆积、氧化应激和慢性炎症状态有关,在全球范围内逐渐增加,对男性生殖能力产生负面影响。在男性生殖领域,循环RNA(circRNA)是一种新兴的研究课题,它是通过反切割而形成的共价闭合RNA分子,在有利于精子生成和建立高质量精子参数方面起着积极作用。然而,肥胖症与精子中circRNA负载功能受损之间的直接关联尚不清楚。在当前的研究中,我们以进食高脂饮食(60%脂肪)的C57BL6/J雄性小鼠作为氧化应激实验模型,研究了高脂饮食对精子形态和运动性以及精子circRNA的影响。我们通过微阵列策略完成了一份完整的精子circRNA内容数据集,并鉴定了差异表达的(DE) circRNA。通过circRNA/miRNA/target网络分析(ceRNET),我们确定了可能参与氧化应激和精子运动途径的circRNA。有趣的是,我们证明了HFD精子在反切割活动方面具有增强的技能,但附睾circRNA的生物合成效率不高。Fused protein in sarcoma (FUS)及其诱导quaking (QKI)可能参与协调这种机制。
Obesity is a pathophysiological disorder associated with adiposity accumulation, oxidative stress, and chronic inflammation state that is progressively increasing in younger population worldwide, negatively affecting male reproductive skills. An emerging topic in the field of male reproduction is circRNAs, covalently closed RNA molecules produced by backsplicing, actively involved in a successful spermatogenesis and in establishing high-quality sperm parameters. However, a direct correlation between obesity and impaired circRNA cargo in spermatozoa (SPZ) remains unclear. In the current work, using C57BL6/J male mice fed with a high-fat diet (HFD, 60% fat) as experimental model of oxidative stress, we investigated the impact of HFD on sperm morphology and motility as well as on spermatic circRNAs. We performed a complete dataset of spermatic circRNA content by a microarray strategy, and differentially expressed (DE)-circRNAs were identified. Using a circRNA/miRNA/target network (ceRNET) analysis, we identified circRNAs potentially involved in oxidative stress and sperm motility pathways. Interestingly, we demonstrated an enhanced skill of HFD sperm in backsplicing activity together with an inefficient epididymal circRNA biogenesis. Fused protein in sarcoma (FUS) and its ability to recruit quaking (QKI) could be involved in orchestrating such mechanism.