Department of Anatomical Sciences and Pathology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran.
Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Mol Biol Rep. 2024 Jun 11;51(1):727. doi: 10.1007/s11033-024-09676-2.
BACKGROUND: The presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor in various testicular cells and spermatozoa suggests a potential role in enhancing spermatogonial and postmeiotic cell development. Moreover, GM-CSF activates the pivotal pathways implicated in sperm motility regulation and glucose metabolism. However, the impact of GM-CSF on testicular biopsies from patients with obstructive azoospermia (OA) remains unexplored. Therefore, this study aimed to investigate the in vitro effects of GM-CSF on the expression of genes related to glucose transporters and signaling pathways, sperm motility, and viability in testicular biopsies. METHODS AND RESULTS: Following testicular sperm extraction from 20 patients diagnosed with OA, each sample was divided into two parts: the experimental samples were incubated with medium containing 2 ng/ml GM-CSF at 37 °C for 60 min, and the control samples were incubated with medium without GM-CSF. Subsequently, the oocytes retrieved from the partner were injected with sperm from the treatment and control groups. The sperm parameters (motility and viability), the expression levels of sperm motility-related genes (PIK3R1, PIK3CA, and AKT1), and the expression levels of sperm energy metabolism-related genes (GLUT1, GLUT3, and GLUT14) were assessed. Furthermore, the fertilization and day 3 embryo development rate and embryo quality were evaluated. Compared with those in the nontreated group, the motility parameters and the mRNA expression levels of PIK3R1, AKT1, and GLUT3 in testicular sperm supplemented with GM-CSF were significantly greater (p < 0.05). However, no significant differences in the mRNA expression of PIK3CA, GLUT1, or GLUT14 were detected. According to the ICSI results, compared with the control group, the GM-CSF treatment group exhibited significantly greater fertilization rates (p = 0.027), Day 3 embryo development rate (p = 0.001), and proportions of good-quality embryos (p = 0.002). CONCLUSIONS: GM-CSF increased the expression of genes related to motility and the energy metabolism pathway and effectively promoted the motility of testis-extracted spermatozoa, consequently yielding positive clinical outcomes.
背景：粒细胞-巨噬细胞集落刺激因子（GM-CSF）及其受体存在于各种睾丸细胞和精子中，提示其在增强精原细胞和减数分裂后细胞发育方面具有潜在作用。此外，GM-CSF 激活了与精子运动调节和葡萄糖代谢相关的关键途径。然而，GM-CSF 对梗阻性无精子症（OA）患者睾丸活检的影响仍未得到探索。因此，本研究旨在研究 GM-CSF 对葡萄糖转运体和信号通路、精子运动和活力相关基因表达的体外影响，在睾丸活检中。
方法和结果：从 20 名诊断为 OA 的患者中进行睾丸精子提取后，将每个样本分为两部分：实验组在含有 2ng/ml GM-CSF 的培养基中于 37°C 孵育 60 分钟，对照组在不含 GM-CSF 的培养基中孵育。随后，从伴侣中取出卵母细胞，并用治疗组和对照组的精子进行注射。评估精子参数（运动和活力）、与精子运动相关的基因（PIK3R1、PIK3CA 和 AKT1）的表达水平以及与精子能量代谢相关的基因（GLUT1、GLUT3 和 GLUT14）的表达水平。此外，评估受精和第 3 天胚胎发育率和胚胎质量。与未处理组相比，GM-CSF 补充的睾丸精子的运动参数和 PIK3R1、AKT1 和 GLUT3 的 mRNA 表达水平显著增加（p<0.05）。然而，PIK3CA、GLUT1 或 GLUT14 的 mRNA 表达无显著差异。根据 ICSI 结果，与对照组相比，GM-CSF 处理组的受精率显著增加（p=0.027），第 3 天胚胎发育率（p=0.001）和优质胚胎比例（p=0.002）。
结论：GM-CSF 增加了与运动和能量代谢途径相关的基因的表达，有效促进了睾丸提取精子的运动，从而产生了积极的临床结果。
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