Abroudi Ali Shakeri, Azizi Hossein, Djamali Melika, Abdullah Hewa Khalid, Qorbanee Ali, Skutella Thomas
Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol, Iran.
Reprod Sci. 2025 Jun 19. doi: 10.1007/s43032-025-01916-5.
Non-obstructive azoospermia (NOA) is a severe form of male infertility characterized by a complete absence of sperm in the ejaculate due to impaired spermatogenesis. While genetic and hormonal factors are known contributors, recent evidence highlights the role of immune dysregulation in NOA pathophysiology. Defense/immunity proteins play a crucial role in maintaining testicular immune homeostasis, but their aberrant expression may contribute to spermatogenic failure. This study analyzed gene expression data from multiple datasets to identify immune-related genes significantly altered in NOA, including IFITM1, CES1, MR1, LSAMP, PRB2, CARD8, and PECAM1. Differential expression analysis revealed upregulation of IFITM1 and PECAM1 and downregulation of CES1, MR1, LSAMP, PRB2, and CARD8, suggesting immune imbalance and oxidative stress contribute to NOA pathogenesis. Additionally, single-cell RNA sequencing confirmed their differential expression in distinct testicular cell populations. Our findings suggest that immune-related pathways, including cytokine signaling, antigen processing, and oxidative stress response, may contribute to NOA pathogenesis. Targeting these molecular pathways could provide novel therapeutic strategies for improving reproductive outcomes in affected individuals.
非梗阻性无精子症（NOA）是男性不育的一种严重形式，其特征是由于精子发生受损，射精中完全没有精子。虽然已知遗传和激素因素是其成因，但最近的证据突出了免疫失调在NOA病理生理学中的作用。防御/免疫蛋白在维持睾丸免疫稳态中起关键作用，但其异常表达可能导致生精失败。本研究分析了多个数据集的基因表达数据，以鉴定在NOA中显著改变的免疫相关基因，包括IFITM1、CES1、MR1、LSAMP、PRB2、CARD8和PECAM1。差异表达分析显示IFITM1和PECAM1上调，而CES1、MR1、LSAMP、PRB2和CARD8下调，表明免疫失衡和氧化应激导致NOA发病机制。此外，单细胞RNA测序证实了它们在不同睾丸细胞群体中的差异表达。我们的研究结果表明，包括细胞因子信号传导、抗原加工和氧化应激反应在内的免疫相关途径可能导致NOA发病机制。针对这些分子途径可能为改善受影响个体的生殖结局提供新的治疗策略。
