Fafula Roman V, Iefremova Ulyana P, Onufrovych Olena K, Maksymyuk Hanna V, Besedina Anna S, Nakonechnyi Iosyf A, Vorobets Dmytro Z, Vorobets Zinoviy D
Department of Biophysics, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine.
Department of Medical Biology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine.
J Med Biochem. 2018 Apr 1;37(2):134-140. doi: 10.1515/jomb-2017-0049. eCollection 2018 Apr.
Infertility 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.
The total NOS, Ca-dependent constitutive (cNOS) and Ca-independent inducible (iNOS) activity and arginase activity were assessed in sperm cells of patients with different forms of pathospermia.
We 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.
These 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.
不孕是一个全球性的重要问题,影响着全球10%-15%的夫妇。一氧化氮(NO)生成的改变也与男性不育的发病机制有关。本研究旨在评估不育患者精子中一氧化氮合酶(NOS)和精氨酸酶活性的变化。
对不同类型精子异常症患者的精子细胞中的总NOS、钙依赖性组成型(cNOS)和钙非依赖性诱导型(iNOS)活性以及精氨酸酶活性进行评估。
我们发现,与生育能力正常、精子正常的男性相比,不育男性精子细胞中的iNOS活性显著增加,但cNOS和精氨酸酶活性显著降低(p<0.001)。与对照组相比,精氨酸酶/NOS比值显著降低。生育潜能降低的患者中iNOS/cNOS比值急剧增加,表明iNOS占主导地位。白细胞精子症患者的iNOS活性表现最为明显。
这些观察结果为不育男性精子细胞中L-精氨酸代谢途径之间的平衡失调提供了证据。这种失衡包括诱导型一氧化氮合酶的大量激活,同时其组成型同工酶受到显著抑制,这表明一氧化氮生成存在紊乱。在生育潜能降低的患者中,精氨酸酶/NOS向iNOS衍生的一氧化氮生成占主导地位转变。