Evaluation of seminal plasma targeted metabolomics (amino acids) following untargeted antioxidant therapy in asthenozoospermia patients: A proposed approach for Personalized Medicine

Abstract Study question To evaluate amino acids profile of Seminal Plasma following untargeted antioxidant therapy in asthenozoospermia patients. Summary answer Random Antioxidant therapy in asthenozoospermia could alter seminal plasma amino acids profile,and any prescribed antioxidant therapy should be based on individual human seminal plasma profile. What is known already The mitochondria of Spermatozoa perform aerobic metabolism and generate reactive oxygen species (ROS). When ROS production exceeds the antioxidant capacity of cells, they cause deleterious effects on sperm functions. Asthenozoospermia patient is defined based on 5th WHO (2010) as having normal morphology >4%, count >15 × 106/ ml, and motility< 32%. One of the important aspects of sperm functions that are affected by ROS is sperm motility. Oral antioxidants seem to be one of the latest trends in counteracting high ROS levels and improving sperm motility for this group of patients. Study design, size, duration Semen samples of asthenozoospermia patients (n = 51) with a mean age (36.3 ±6) were collected after 3 – 5 days of abstention. Routine antioxidant supplementation (Vitamin E 400 IU / day + Selenium 60 mg / day + Folic acid 5 mg / day) was prescribed daily for 3 months. Participants/materials, setting, methods Semen analysis was done before and after antioxidant therapy. The seminal plasma amino acids profile was analyzed by using HILIC-LC-MS/MS. In detail, 34 amino acids were evaluated quantitatively before and after administrating supplementation. Main results and the role of chance In our study MetaboAnalyst, software was utilized for metabolomics investigations. The volcano plot appeared a noteworthy diminish in 12 amino acids after antioxidant treatment. The foremost noticeable decrease was seen in Beta-Aminoisobutyric and L-tryptophan as Improvers of sperm motility, also hydroxyproline which has to be present within the normal semen had a significant decrease after antioxidant therapy. Interestingly, after antioxidant treatment, only sperm count increased (163 × 106 ± 9) compared with the pre-treatment group (104 × 106 ± 6) but not sperm motility. Moreover based on the Enrichment Analysis information; Urea Cycle, Ammonia Recycling, and Aspartate Metabolism are the foremost prevailing cycles in asthenozoospermia patients. The literature recommends that the Urea cycle has a negative correlation with sperm count and Ammonia Recycling contains a negative relationship with sperm motility in infertile men. Our findings propose that the most important cause of sperm count increase after the mentioned treatment is suppression of the Urea cycle without having any effect on Ammonia Recycling to improve sperm motility, which was in contrast with our objectives. thereupon any prescribed antioxidant treatment ought to be based on individual human seminal plasma profiles and metabolomics pathways to have the desired result at the end. Limitations, reasons for caution The main limitations of this study are the exact patient selection and involving the pure asthenozoospermia patients in the study. Wider implications of the findings Knowing the exact etiology of each affected semen parameter and normal metabolomics of sperm and seminal plasma can prepare important data for personalized medicine and the administration of suitable interventions to improve sperm quality and male fertility status. Trial registration number not applicable