158 5 REPRODUCTIONRESEARCH Melatonin rescues impaired penetration ability of human spermatozoa induced by mitochondrial dysfunction Xue-Ying Zhang1,*, Yi-Meng Xiong1,*, Ya-Jing Tan2, Li Wang2, Rong Li2, Yong Zhang2, Xin-Mei Liu2, Xian-Hua Lin2, Li Jin2, Yu-Ting Hu2, Zhen-Hua Tang2, Zheng-Mu Wu2, Feng-Hua Yin2, Zheng-Quan Wang2, Ye Xiao2, Jian-Zhong Sheng1,3 and He-Feng Huang1,2,4 1The Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou, Zhejiang, China, 2The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, 3Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China and 4Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China Correspondence should be addressed to H-F Huang; Email:
[email protected] *(X-Y Zhang and Y-M Xiong contributed equally to this work) Abstract Fertilization failure often occurs during in vitro fertilization (IVF) cycles despite apparently normal sperm and oocytes. Accumulating evidence suggests that mitochondria play crucial roles in the regulation of sperm function and male fertility. 3-Nitrophthalic acid (3-NPA) can induce oxidative stress in mitochondria, and melatonin, as an antioxidant, can improve mitochondrial function by reducing mitochondrial oxidative stress. The role of sperm mitochondrial dysfunction in fertilization failure during IVF is unclear. The present study revealed that spermatozoa with low, or poor, fertilization rates had swollen mitochondria, increased mitochondria- derived ROS, and attenuated mitochondrial respiratory capacity. 3-NPA treatment enhanced mitochondrial dysfunction in sperm. Spermatozoa with poor fertilization rates, and spermatozoa treated with 3-NPA, had reduced penetration ability.