MAEL基因功能喪失會破壞粒腺體功能並損害人類精子活動力

鄭裕生¹、陳幸儀¹、林于巧^２、林宗彥^２、翁涵育¹、林永明¹、林世杰^３

國立成功大學醫學院附設醫院泌尿部¹，成大斗六分院²，國立成功大學醫學院基礎醫學研究所^３

Loss of MAEL Expression Sabotages Mitochondrial Function and Impairs Human Sperm Motility

Yu-Sheng Cheng¹, Sin-Yi Chen¹, Yu-Chiao Lin², Tsung-Yen Lin², Han-Yu Weng¹,Yung-Ming Lin¹, Shih-Chieh Lin³

Department of Urology, National Cheng Kung University Hospital¹; Department of Surgery, Division of Urology, National Cheng Kung University Hospital Dou-Liou Branch, Yunlin, Taiwan²; The Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan^３

Objective:

MAEL was known to participate in the piRNA-mediated defense system to protect the germline from retrotransposons. We previously reported that the MAEL promoter's aberrant methylation might contribute to one of the causes of spermatogenic failure in infertile men. However, there is no report for MAEL expression in human ejaculated sperm. Thus, this study focused on determining the MAEL expression in ejaculated spermatozoa and exploring the gene function regarding to sperm motility. 

Materials and methods:

The Institutional Review Board approved this study of the National Cheng Kung University Hospital, Tainan, Taiwan (A-ER-102-432). MAEL in human spermatozoa was investigated by western blotting, immunofluorescence staining, and transmission electron microscope(TEM). In addition, the mitochondrial function and sperm features after MAEL knockdown were evaluated. We compared the MAEL protein in the human ejaculated sperm of 40 normospermic versus 30 asthenozoospermic men. The correlation between MAEL protein levels and sperm features was analyzed statistically.

Results:

Western blot analysis further confirmed MAEL proteins in human ejaculated sperm. MAEL protein is detected in the neck, mid-piece, and tail of sperm by immunofluorescence staining. TEM illustrated MAEL is mainly in the mitochondria of the middle piece. Knockdown of MAEL sabotaged mitochondria function and reduced ATP production, which impaired sperm motility without affecting sperm count and vitality. Moreover, significantly decreased MAEL has been noted in ejaculated sperm of the asthenozoospermic group compared to the normozoospermic group. Total motile sperm count (TMSC) was positively correlated with protein levels of MAEL.

Conclusions:

Loss of MAEL results in mitochondrial dysfunction and motility impairment of human ejaculated sperm. In addition, the lower levels of sperm MAEL may account for the causes of asthenozoospermia.

Keywords: MAEL; male infertility; mitochondria; asthenozoospermia