Non-obstructive azoospermia (NOA) and obstructive azoospermia (OA) are the main classifications of severe male infertility, but the molecular mechanism of NOA remains poorly understood. This study aimed to identify potential biomarkers and pathological mechanisms by comparing the proteomic differences in testicular tissues of NOA and OA patients. Through proteomic analysis based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) of testicular samples from 5 NOA patients and 5 OA patients, we identified 5264 proteins, among which 717 differentially expressed proteins (DEPs) were found between the two groups (242 upregulated and 475 downregulated in NOA). Bioinformatics analysis indicated that these DEPs were significantly associated with reproductive development, gametogenesis, and cell structural stability. On the basis of this, six candidate proteins, including dysferlin (DYSF), myoferlin (MYOF), mitsugumin 53 (MG53), cluster of differentiation 63 (CD63), caveolin-3 (CAV3), and calpain-3 (CAPN3), were selected from the DEPs and verified in an expanded sample set (37 NOA cases and 28 OA cases) through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, confirming their dysregulation in NOA. These findings provide new proteomic insights into NOA, highlighting the disruption of membrane repair and structural pathways, and offer potential biomarkers for understanding its pathogenesis.
Asian journal of andrology. 2026 May 29 [Epub ahead of print]
Zhi Wang, Xiao-Dong Li, Wei-Min Shao, Dong-Xuan Zheng, Xiao-Qiang Xiang, Heng-Qing An, Jian-Hua Yang
Department of Pharmacy, The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830011, China., Department of Urology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China., Center for Reproductive Medicine, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China., College of Pharmacy, Xinjiang Medical University, Urumqi 830054, China., Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai 201203, China.