Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, China.
J Control Release. 2023 Oct;362:58-69. doi: 10.1016/j.jconrel.2023.08.031. Epub 2023 Aug 26.
Asthenozoospermia, characterized by poor sperm motility, is a common cause of male infertility. Improving energy metabolism and alleviating oxidative stress through drug regimens are potential therapeutic strategies. In this study, we observed upregulated miR-24-3p levels in asthenozoospermia spermatozoa, contributing to energy metabolism disorder and oxidative stress by reducing GSK3β expression. Thus, reducing miR-24-3p levels using drugs is expected to improve sperm motility. The blood-testis barrier (BTB) protects the testis from xenobiotics and drugs. In this study, we found that Sertoli cell-derived small extracellular vesicles (SC-sEV) can traverse the BTB and enter germ cells. We successfully loaded miR-24-3p inhibitor into SC-sEV, creating the nano-drug SC-sEV@miR-24-3p inhibitor, which effectively delivers miR-24-3p inhibitor into germ cells. In a gossypol-induced mouse asthenozoospermia model, administration of SC-sEV@miR-24-3p inhibitor significantly improved sperm motility, in vitro fertilization success, and blastocyst formation rates. As anticipated, it also improved the litter size of asthenozoospermia mice. These results suggest that SC-sEV@miR-24-3p inhibitor holds promise as a potential clinical treatment for asthenospermia.
弱精子症的特征是精子运动能力差，是男性不育的常见原因。通过药物治疗改善能量代谢和减轻氧化应激是潜在的治疗策略。在这项研究中，我们观察到弱精子症精子中 miR-24-3p 水平上调，通过降低 GSK3β 表达导致能量代谢紊乱和氧化应激。因此，使用药物降低 miR-24-3p 水平有望改善精子运动能力。血睾屏障（BTB）可保护睾丸免受外源性物质和药物的侵害。在这项研究中，我们发现支持细胞衍生的小细胞外囊泡（SC-sEV）可以穿透 BTB 并进入生殖细胞。我们成功地将 miR-24-3p 抑制剂加载到 SC-sEV 中，创造了纳米药物 SC-sEV@miR-24-3p 抑制剂，可有效将 miR-24-3p 抑制剂递送到生殖细胞中。在棉酚诱导的弱精子症小鼠模型中，给予 SC-sEV@miR-24-3p 抑制剂可显著提高精子运动能力、体外受精成功率和囊胚形成率。正如预期的那样，它还提高了弱精子症小鼠的产仔数。这些结果表明，SC-sEV@miR-24-3p 抑制剂有望成为弱精子症的一种潜在临床治疗方法。
