Loss of ovarian hormones modulates nucleic acid content of circulating extracellular vesicles in response to acute exercise

Loss of ovarian hormones (i.e., menopause) leads to negative effects on metabolic health. While exercise offers significant benefits, it seems to be insufficient to completely reverse these changes. The mechanisms by which exercise conveys the effects throughout the body are still poorly understood. Extracellular vesicles (EVs) are released into circulation during exercise. EVs carry small non-coding RNAs (sRNAs), such as microRNAs (miRs), which are proposed as mediators of the effects of exercise. In this study, we examined the effect of loss of ovarian hormones and acute exercise in the sRNA cargo of EV and HDL particles in female rats. We show for the first time that loss of ovarian hormones affects specifically the nucleic acid cargo of circulating EVs. In addition, we show that the loss of ovarian hormones diminishes the miR response to acute exercise in EV particles. The study sample consisted of 40 female Wistar Hans rats. Half of the rats (n=20) underwent ovariectomy (OVX), resulting in the loss of ovarian hormones and the other half (n=20) was predisposed to sham surgery without the removal of ovaries. In both groups, half of the rats (n=10) performed maximal running test (max) to induce an acute exercise stimulus and the other 10 served as control. Hence, there were 4 groups of rats, with 10 rats in each group: sham/control, sham/max, OVX/control, and OVX/max.

卵巢激素缺失（即绝经）会对代谢健康产生负面影响。尽管运动可带来显著益处，但似乎不足以完全逆转此类代谢改变。运动将其效应传递至全身的具体机制仍有待阐明。运动过程中，细胞外囊泡（Extracellular vesicles, EVs）会被释放入循环系统。细胞外囊泡携带小型非编码RNA（small non-coding RNAs, sRNAs），例如微小RNA（microRNAs, miRs），这类RNA被认为是介导运动效应的关键因子。本研究以雌性大鼠为实验对象，探究了卵巢激素缺失与急性运动对细胞外囊泡及高密度脂蛋白（High-Density Lipoprotein, HDL）颗粒所载小型非编码RNA载荷的影响。本研究首次证实，卵巢激素缺失会特异性影响循环中细胞外囊泡的核酸载荷。此外，本研究发现卵巢激素缺失会削弱细胞外囊泡颗粒对急性运动的微小RNA应答反应。本研究的实验样本共包含40只雌性Wistar Hans大鼠。其中20只大鼠接受卵巢切除术（Ovariectomy, OVX）以造成卵巢激素缺失，剩余20只则接受假手术，不摘除卵巢。两组中各有10只大鼠进行最大跑台运动测试（maximal running test, max）以施加急性运动刺激，其余10只作为对照。最终共分为4组大鼠，每组10只：假手术对照（sham/control）组、假手术运动（sham/max）组、卵巢切除对照（OVX/control）组以及卵巢切除运动（OVX/max）组。