The Activated AMPK/mTORC2 Signaling Pathway Associated with Oxidative Stress in Seminal Plasma Contributes to Idiopathic Asthenozoospermia

Author:

Cao Nannan12,Hu Chunhui3,Xia Bintong4,He Yan12,Huang Jiaolong2,Yuan Zhicheng5,Deng Jie2ORCID,Duan Peng26ORCID

Affiliation:

1. Postgraduate Union Training Base of Jinzhou Medical University, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000 Hubei Province, China

2. Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Xiangyang City, Department of Obstetrics and Gynaecology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000 Hubei Province, China

3. Department of Clinical Laboratory, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000 Hubei Province, China

4. Department of Urology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000 Hubei Province, China

5. The Fourth Clinical Faculty, Hubei University of Medicine, Shiyan, 44200 Hubei Province, China

6. Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, 442000 Hubei Province, China

Abstract

Asthenozoospermia is a common form of abnormal sperm quality in idiopathic male infertility. While most sperm-mediated causes have been investigated in detail, the significance of seminal plasma has been neglected. Herein, we aimed to investigate the possible pathogenic factors leading to decreased sperm motility based on seminal plasma. Semen was collected from normo- (NOR, n = 70 ), idiopathic oligo- (OLI, n = 57 ), and idiopathic asthenozoospermic (AST, n = 53 ) patients. Using attenuated total reflection-Fourier transform infrared coupled with chemometrics, distinct differences in the biochemical compositions of nucleic acids, protein structure (amides I, II, and III), lipids, and carbohydrates in seminal plasma of AST were observed when compared to NOR and OLI. Compared with NOR and OLI, the levels of peptide aggregation, protein phosphorylation, unsaturated fatty acid, and lipid to protein ratio were significantly increased in AST; however, the level of lipid saturation was significantly decreased in seminal plasma of AST. Compared with NOR, the levels of ROS, MDA, 8-iso-prostaglandin F2α (8-isoPGF2α), and the ratio of phospho-AMPKα/AMPKα1 were significantly increased in AST; however, the levels of SOD, glutathione S-transferase (GSTs), protein carbonyl derivative (PC), and the ratio of phospho-Rictor/Rictor were significantly decreased in seminal plasma of AST. Changes of the AMPK/mTORC2 signaling in the seminal microenvironment possibly induce abnormal glucose and lipid metabolism, which impairs energy production. Oxidative stress potentially damages seminal plasma lipids and proteins, which in turn leads to impaired sperm structure and function. These findings provide evidence that the changes in seminal plasma compositions, oxidative stress, and activation of the AMPK/mTORC2 signaling contribute to the development of asthenozoospermia.

Funder

Xiangyang No. 1 People’s Hospital

Publisher

Hindawi Limited

Subject

Cell Biology,Aging,General Medicine,Biochemistry

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