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

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.

Oxidative Stress Biomarkers in Male Infertility: Established Methodologies and Future Perspectives

“…If the damage is mild, then spermatozoa are able to repair it; however, extensive damage leads to DNA fragmentation and apoptosis, decreasing the quality of the seminal fluid [35]. Furthermore, the sperm membrane contains high levels of polyunsaturated fatty acids, which are the main targets of ROS, thereby reducing sperm motility [36].…”

Association of Endogenous Seminal L-Carnitine Levels with Post-Thaw Semen Parameters in Humans

“…Spermatozoa are highly susceptible to the deleterious effects of excessive ROS generation due to the high amount of polyunsaturated fatty acids (PUFAs) in the plasma membrane susceptible to lipid peroxidation [12]. Lipid peroxidation can lead to loss of membrane fluidity and integrity and can affect sperm structure and function [13,14]. Increased levels of ROS in seminal plasma are associated with reduced sperm count [15] and sperm motility [16,17] and increased DNA fragmentation [18].…”