Oxidative stress in the pathophysiology of male infertility

Abstract

Most biological systems depend on preservation of equilibrium. Within the male reproductive system, oxidative harmony is crucial to fertility. Reactive oxygen species (ROS) make functional contributions at appropriate concentrations, but quickly become destructive if left unchecked. It is important to understand the key oxidative players, their mechanisms and the implications in male infertility. In this review, we discuss the role of redox biology in male reproduction, consequences of oxidative stress and their involvement in pathogenesis of male infertility and assisted reproductive outcomes. 1.1 | Oxidative stress and sources of ROS Given the premise of aerobic life, reactive oxygen species play a paradoxical role, both critical for regulation of cellular function and capable of exerting significant damage on cells and molecules (Morrell, 2008). Oxidative stress is defined as an imbalance between ROS and the antioxidants attempting to keep them in check (Sies, 2015). ROS exist in both endogenous and exogenous forms. Endogenous players include superoxide (O − 2), generated via mitochondrial redox reactions, as well as hydrogen peroxide (H 2 O 2) and the hydroxyl radical (OH −). Mitochondrial dysfunction results in the excessive accumulation of these products (Hayyan, Hashim, & AlNashef, 2016). Furthermore, immune cells employ redox reactions as anti-pathogen tools, generating ROS in the process (Sies, 1993). Nitric oxide is one in a collection of reactive nitrogen species (RNS), which also include peroxynitrite, nitroxyl and nitrosyl compounds (Doshi, Khullar, Sharma, & Agarwal, 2012). The product of the reaction between nitric oxide and superoxide, peroxynitrite, exerts oxidative stress on spermatozoa via direct molecular damage and interference with key signalling pathways (Rosselli, Keller, & Dubey, 1998). In this way, ROS hold the power to instigate exponential destruction (Henkel, Samanta, & Agarwal, 2018). Exogenous sources of ROS include tobacco smoke, heavy metals and ionizing radiation (Birben, Sahiner, Sackesen, Erzurum, & Kalayci, 2012). Oxygen free radicals in cigarette tar and tobacco smoke,

Redox potential in human semen: Validation and qualification of the MiOX sys assay

“…Measurement of OS in semen is highly predictive of abnormal semen parameters and infertility Ritchie & Ko, 2020). It is therefore paramount that a diagnostic assessment that measures the level of ROS becomes integrated into routine semen analysis.…”

Supplementing post‐wash asthenozoospermic human spermatozoa with coenzyme Q10 for 1 hr in vitro improves sperm motility, but not oxidative stress

“…Oxidative stress causes oxidative damage to spermatozoa, and it is a common underlying aetiology of infertility in men (Alahmar, 2019; Barati, Nikzad, & Karimian, 2020; Bisht, Faiq, Tolahunase, & Dada, 2017; Ritchie & Ko, 2020). Therefore, supplementation of anti‐oxidants has been suggested for treatment of male infertility.…”

Docosahexaenoic acid in the treatment of male infertility caused by high sperm DNA fragmentation

“…Это также одна из причин неразвивающейся беременности, спонтанного аборта и неудачных попыток экстракорпорального оплодотворения [7][8][9][10]. Так как окислительный стресс является ведущим механизмом повреждения генетического материала сперматозоидов, антиоксидантная терапия была предложена в качестве одного из основных методов лечения мужского бесплодия, ассоциированного с высоким уровнем фрагментации ДНК сперматозоидов [11][12][13][14][15][16]. В исследованиях оценена эффективность многих антиоксидантов, однако полученные результаты противоречивы [14,[16][17][18][19][20].…”

“…Применение ПНЖК в клинических исследованиях снижало интенсивность воспалительной симптоматики и улучшало состояние пациентов с болезнью Крона, ревматоидным артритом, кератоконъюнктивитом, периодонтитом и гингивитом [40][41][42][43][44]. Окислительный стресс считается основным механизмом повреждения генетического материала сперматозоидов, а главным источником активных форм кислорода в эякуляте являются лейкоциты [11][12][13][45][46][47]. Воспалительный процесс в добавочных половых железах обусловливает повышение концентрации лейкоцитов в эякуляте и, таким образом, может становиться причиной повышения продукции АФК и развития окислительного стресса [45][46][47].…”