GPX4 表現與男性不孕症中粒線體功能及精子品質之相關性

林宗彥^1.2、陳幸儀²、侯琇瓊²、劉佳旻³、林世杰^4*、鄭裕生^2*

¹國立成功大學附設醫院斗六分院泌尿部、²國立成功大學附設醫院泌尿部、³衛生福利部台南醫院泌尿科、⁴國立成功大學基礎醫學研究所

GPX4 Is Associated with Mitochondrial Function and Sperm Quality in Male Infertility

Tsung-Yen Lin^1,2, Hsing-Yi Chen², Hsiu-Chiung Hou², Chia-Min Liu³, Shih-Chieh Lin^2*, Yu-Sheng Cheng^3*

¹Division of Urology, Department of Surgery, National Cheng Kung University Hospital Dou-Liou Branch, Yunlin, Taiwan, ²Department of Urology, Medical College and Hospital, National Cheng-Kung University, Tainan, Taiwan, ³Department of Urology, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan, and ⁴Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Abstract

Purpose:

To investigate the role of GPX4 in spermatogenesis and its association with mitochondrial structure, function, and sperm quality at the molecular level.

Materials and Methods:

Human sperm samples were analyzed to assess the association between GPX4 expression and total motile sperm count (TMSC). MAEL–GPX4 interaction was evaluated using RNA immunoprecipitation. MAEL knockdown was performed to assess its regulatory effect on GPX4 expression. Mitochondrial function was evaluated by PINK1 expression and ATP production. Testicular GPX4 expression in different spermatogenic conditions (normal spermatogenesis [NR], hypospermatogenesis [HS], maturation arrest [MA], and Sertoli cell-only syndrome [SCOS]) was analyzed by immunohistochemistry. Transmission electron microscopy (TEM) combined with immunogold labeling was used to localize GPX4 in human sperm and assess mitochondrial ultrastructural changes.

Results:

GPX4 expression positively correlated with TMSC and was significantly reduced in men with impaired spermatogenesis, particularly MA and SCOS. RNA immunoprecipitation demonstrated that MAEL directly interacts with GPX4 mRNA. MAEL knockdown significantly reduced GPX4 expression, accompanied by increased PINK1 expression and decreased ATP production, indicating mitochondrial dysfunction. Immunogold TEM revealed that GPX4 localizes to the mitochondrial sheath of sperm. In patients with abnormal spermatogenesis, mitochondrial structural disorganization and reduced GPX4-associated labeling were observed.   

Conclusions:

GPX4 plays a critical role in maintaining mitochondrial integrity and energy production during spermatogenesis. MAEL regulates GPX4 expression, and disruption of this pathway leads to mitochondrial dysfunction and impaired sperm quality.