Sperm metabolomic signatures of asthenozoospermia and teratozoospermia in Chinese reproductive-age men.

Journal: Scientific reports
Published Date:

Abstract

Asthenozoospermia and teratozoospermia are common causes of male infertility. Despite their prevalence, the underlying metabolic mechanisms remain poorly understood. In this study, we conducted targeted metabolomic profiling of sperm samples from 131 Chinese reproductive-age men (48 normozoospermic controls, 40 asthenozoospermic patients, and 43 teratozoospermic patients) to identify distinct metabolic signatures associated with these conditions. We identified 47 significantly altered metabolites in asthenozoospermia compared to normozoospermia (18 downregulated and 29 upregulated). In teratozoospermia, 25 metabolites showed significant changes compared to normozoospermia (10 downregulated, 15 upregulated). These differential metabolites, along with others identified through machine learning as relevant, are implicated in key pathways including energy metabolism, lipid metabolism, and amino acid metabolism. Alterations, such as those in corticosterone and hypoxanthine, suggest potential impacts on redox balance and stress responses. Using machine learning approaches, we developed diagnostic models for asthenozoospermia and teratozoospermia diagnosis, with the Glmnet model showing strong performance (AUC = 0.99 for asthenozoospermia, AUC = 0.9997 for teratozoospermia), although these results require external validation. Two metabolites emerged as candidate diagnostic biomarkers: corticosterone reveals common metabolic disturbances in both pathological conditions, and arachidate specifically indicates impaired lipid metabolism in asthenozoospermia. These findings improve our understanding of the metabolic basis of sperm dysfunction, and highlight the potential of sperm metabolomics as a powerful tool for diagnosing and managing male infertility.

Authors

  • Youzhu Li
    State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Repro-duction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding (MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100083, China.
  • Zhonghua Lu
  • Jingu Li
    Department of Reproductive Medicine, Quanzhou Women's and Children's Hospital, Quanzhou, 362000, China.
  • Ling Cheng
    Centre for Cellular Biology and Signalling, Zhejiang University-University of Edinburgh (ZJU-UoE) Institute, 718 East Haizhou Road, Haining 314400, China.
  • Yuanyuan Ye
    Department of Reproductive Medicine, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, 361001, China.
  • Song Xu
    Jinling Clinical Medical College, Nanjing Medical University,Nanjing,Jiangsu 210002,China.
  • Junfeng Tan
    School of Public Health, Xiamen University, Xiamen, 361102, Fujian, China.
  • Lifeng Zheng
    State Key Laboratory of Coordination Chemistry, Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Engineering Research Center of Photoresist Materials of Ministry of Education, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
  • Huiyi Xie
    Department of Reproductive Medicine, Quanzhou Women's and Children's Hospital, Quanzhou, 362000, China.
  • Qisheng Zhong
    Shimadzu Global COE for Application & Technical Development, Guangzhou, Guangdong 510010, China.
  • Jiaqi Liu
  • Yunfan Yang
    Guangzhou Analysis Center Analytical & Measuring Instruments Division, Shimadzu (China) Co., LTD, Guangzhou, 510656, China.
  • Rui Guo
    College of Chemistry&Chemical Engineering, Xiamen University, Xiamen 361005, China.
  • Guoshi Liu
    State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Repro-duction of the Ministry of Agriculture, Frontiers Science Center for Molecular Design Breeding (MOE), College of Animal Science and Technology, China Agricultural University, Beijing, 100083, China. gshliu@cau.edu.cn.