Relationship of Seminal Oxidation-Reduction Potential with Sperm DNA Integrity and pH in Idiopathic Infertile Patients

Abstract

Seminal oxidative stress (OS) is one of the most promising factors to describe the causes of idiopathic male infertility. Redox balance is essential in several biological processes related to fertility, so alterations such as high reactive oxygen species (ROS) levels or low antioxidant agent levels can compromise it. MiOXSYS has been developed to evaluate the seminal static oxidation-reduction potential (sORP) and it has been proposed as an effective diagnostic biomarker. However, its relationship with parameters like sperm DNA fragmentation (SDF), chromatin compaction status or seminal pH requires further analysis, making it the object of this study. Semen and sORP analysis were performed for all samples. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL) and Comet assay were used to assess SDF and chromomycin a3 (CMA3) test to assess sperm chromatin compaction. Regarding sORP measures, it was found that alkaline pH has an effect on sample reproducibility. To our knowledge, this unexpected effect has not been previously described. A statistical analysis showed that sORP correlated negatively with CMA3 positive cells and sperm motility, but not with SDF. As redox dysregulation, which occurs mainly at the testicular and epididymal level, causes chromatin compaction problems and leaves DNA exposed to damage, an excess of ROS could be counterbalanced further by a seminal supply of antioxidant molecules, explaining the negative correlation with CMA3 positive cells but no correlation with SDF. Our results show that the study of idiopathic infertility would benefit from a combined approach comprising OS analysis, SDF and chromatin compaction analysis.

Chronic Inflammation Impairs Male Fertility—A Case-Control Study in Ulcerative Colitis Patients

“…According to Karabulut et al, an excessive ORP level results in a decrease in sperm concentration, total motility, and progressive motility, which is confirmed by the results of the presented study [43]. Similar results were obtained by Garcia-Segura, S. et al; however, only with respect to sperm motility [44]. An unfavourable effect of oxidative stress on sperm DNA fragmentation observed in our study also was described by Muratori et al [45] It may be expected that intensification of DNA fragmentation, as well as a decrease in some semen parameters in the inflammatory bowel disease (IBD) group may result from disorders in the oxidation-reduction potential of semen (increase in ORP) [46].…”

“…According to Karabulut et al, an excessive ORP level results in a decrease in sperm concentration, total motility, and progressive motility, which is confirmed by the results of the presented study [ 43 ]. Similar results were obtained by Garcia-Segura, S. et al; however, only with respect to sperm motility [ 44 ]. An unfavourable effect of oxidative stress on sperm DNA fragmentation observed in our study also was described by Muratori et al [ 45 ]…”

The Sixth Edition of the WHO Manual for Human Semen Analysis: A Critical Review and SWOT Analysis

“…Due to the production of excessive amounts of ROS in numerous medical conditions, including varicocele [43], leukocytospermia [44], diabetes mellitus [45], and obesity [46], seminal OS develops. Consequently, OS negatively affects all sperm functions, including sperm DNA integrity [47,48], and thereby the fertilization process and reproductive outcomes [49][50][51][52][53][54][55].…”

“…Unfortunately, this 6th Edition of the WHO manual is lacking recently published evidence indicating the predictive power of seminal OS as determined by means of the ORP [48,[57][58][59][60]. Similarly, the luminometric determination of seminal OS resulted in a significant prediction of good embryo cleavage and blastocyst quality after intracytoplasmic sperm injection (ICSI) in the low OS group [61].…”

The combined effect of lifestyle intervention and antioxidant therapy on sperm DNA fragmentation and seminal oxidative stress in IVF patients: a pilot study

“…This automated method has been suggested as a less time-consuming and more efficient way of assessing the complete redox balance of all known and unknown oxidants and antioxidants in semen (14). However, until now, results are conflicting regarding the correlation between the seminal ORP level, routine semen parameters, and DFI (15)(16)(17). Moreover, to suggest a clinical implementation of ORP measurement and DFI testing in daily practice, a potential causal inference needs to be made.…”