Alterations in Arginase-No-Synthase System of Spermatozoa in Human Subjects with Different Fertility Potential

Abstract

SummaryBackgroundInfertility is an important worldwide problem which affects 10–15% of couples globally. Altered NO production has also been implicated in the pathogenesis of the male infertility. The present study was designed to evaluate the changes in the activity of NO-synthase (NOS) and arginase in spermatozoa of patients with infertility.MethodsThe total NOS, Ca2+-dependent constitutive (cNOS) and Ca2+-independent inducible (iNOS) activity and arginase activity were assessed in sperm cells of patients with different forms of pathospermia.ResultsWe found a significant increase in iNOS activity, but significantly decreased cNOS and arginase activity in sperm cells of infertile men vs fertile, normozoospermic men (p<0.001). The arginase/NOS ratio significantly decreased compared to control group. The iNOS/cNOS ratio was drastically increased in patients with decreased fertility potential indicating predominance of iNOS. Men with leuko cytospermia were distinguished to have the most express iNOS activity.ConclusionsThese observations provide evidence for a disturbed balance between the L-arginine metabolic pathways in sperm cells of infertile men. This imbalance includes the considerable activation of the inducible isoform of NO-synthase accompanied by significant inhibition of its constitutive isoform which indicates disturbances in NO production. In patients with decreased fertility potential the arginase/NOS was shifted towards predominance of iNOS-derived NO production.

The relationships between changes in main biochemical parameters in sperm cells of infertile men

“…Under semen abnormalities, the redistribution of activities in NOS system with their shift towards the Ca 2+ independent iNOS was revealed. This indicates dysmetabolic changes in NO biosynthesis, namely its hyperproduction [2]. According to the results of factor analysis, none of indices of this system form a cluster with other biochemical indices in the pathozoospermic samples.…”

“…Our former [2][3][4]9] indicate a direction of changes in the biochemical parameters in sperm cells of the infertile men with various forms of semen abnormalities, although it is often a question of combining these forms according to certain criteria. It is known that cluster analysis allows grouping different studied groups at the same values of indices.…”

“…For analysis, the results of our previous studies were used performed on sperm cells of the infertile men with different forms of semen abnormalities [2][3][4]9]. The data of 56 men who passed from January 2014 to April 2017 a primary infertility survey in a con sultative polyclinics of Lviv regional clinical hospital were analyzed.…”

“…In previous studies, we have shown that pathospermia was associated with the development of oxidative stress, expressed as an increase in the thiobarbituric acid reactive substances (TBARS) level in sperm cells of the infertile men and the inverse correlation between TBARS level and spermatozoa concentration in the ejaculate and their motility [4]. It was found that in sperm of infertile men with various forms of semen abnormalities the activity of constitutive isoforms of NO-synthase (cNOS) and arginase were suppressed and the activity of inducible form (iNOS) was increased compensatory [2]. This indicates the hypeproduction of NO.…”

Gender-Specific Differences of Oxidative Processes in the Population of Circulating Neutrophils of Rats in a Setting of Prolonged Administration of Monosodium Glutamate

“…Nitric oxide synthase (NOS) activity assay in the lung tissue supernatant was performed by monitoring the rate of conversion of L-arginine into citrulline [15]. Total protein was measured with Lowry assay [16].…”