Role of nuclear factor erythroid 2-related factor 2 (Nrf2) in female and male fertility.

Oxidative stress refers to a condition where there is an imbalance between the production of reactive oxygen species and their removal by antioxidants. While the function of reactive oxygen species as specific second messengers under physiological conditions is necessary, their overproduction can lead to numerous instances of cell and tissue damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of many cytoprotective genes that respond to redox stresses. Nrf2 is regularly degraded by kelch-like ECH-associated protein 1 through the ubiquitin-proteasome pathway. The kelch-like ECH-associated protein 1 and Nrf2 complex have attracted attention in both basic and clinical infertility research fields. Oxidative stress is implicated in the pathogenesis of female infertility, including primary ovarian insufficiency, polycystic ovarian syndrome, and endometriosis, as well as male infertility, namely varicocele, cryptorchidism, spermatic cord torsion, and orchitis. Most scientists believe that Nrf2 is a potential therapeutic method in female and male infertility disorders due to its antioxidant effect. Here, the potential roles of oxidative stress and Nrf2 in female and male infertility disorders are reviewed. Moreover, the key role of Nrf2 in the inhibition or induction of these diseases is discussed.

Protective roles of seminal plasma exosomes and microvesicles during human sperm cryopreservation.

RESEARCH QUESTION: Do seminal plasma microvesicles and exosomes, as two subtypes of extracellular vesicles, exert cryoprotective properties in sperm cryopreservation? DESIGN: Microvesicles and exosomes isolated from normozoospermic semen samples (n = 10) by serial ultracentrifugation were determined using scanning electron microscopy, dynamic light scattering and western blot analysis. The interactions between extracellular vesicles and spermatozoa were detected using Dil labelling. Purified spermatozoa from different normozoospermic samples (n = 25) were then treated individually with exosomes or microvesicles for 1 h and subsequently cryopreserved. The effects of extracellular vesicles during cryopreservation were investigated by determining post-thaw sperm motility, morphology, viability, reactive oxygen species (ROS) generation, lipid peroxidation, total antioxidant capacity (TAC), mitochondrial membrane potential (MMP), DNA integrity, and apoptosis rate. RESULTS: Microvesicles and exosomes displayed a round-shape morphology, with about 70% of exosomes ranging from 43-144 nm, microvesicles ranging from 144.5-486 nm and both expressed tetraspanin markers. Fluorescence microscopy showed that exosomes and microvesicles absorbed mainly in the sperm head and less frequently in the neck and tail. The post-thawing results indicated that the diluent with exosomes or microvesicles had improved sperm motility (P = 0.007), morphology (P < 0.001) and viability (P < 0.001) compared with untreated samples. The ROS levels decreased significantly (P = 0.001), with a consequent decrease in DNA damage (P = 0.001). The TAC activity (P = 0.001) and MMP levels (P = 0.001) were also significantly improved; levels of malondialdehyde (MDA) (P = 0.62) and apoptosis rate (P = 1.000) remained unchanged. CONCLUSION: Seminal plasma microvesicles and exosomes could protect spermatozoa from cryopreservation chilling injuries.

COVID-19 and varicocele: The possible overlap factors and the common therapeutic approaches.

Varicocele is recognized as one of the main attributable causes of male infertility which can affect spermatogenesis by various pathophysiological mechanisms. Recent studies have identified oxidative stress and reduction in antioxidant, hyperthermia, hypoxia, hormonal dysfunction, and inflammatory conditions as major factors in the pathophysiology of varicocele, all of which have known direct associations with the coronavirus disease 2019 (COVID-19) and can significantly increase the risk of detrimental COVID-19-related outcomes. Emerging data have shown an association between COVID-19 and inflammation, overproduction of cytokine, and other pathophysiological processes. The present review, summarizes the current understanding of the pathophysiology of varicocele and investigates the potential correlation between the severity of COVID-19 and the varicocele disease. In addition, various possible treatments which can be effective in both diseases were examined. Despite numerous challenges associated with the prevalence of COVID-19 in healthcare systems in infected countries, special attention should be given to maintaining a high level of care for complex patients with a pre-existing disease such as varicocele and providing appropriate practical advice for optimal control of the COVID-19 disease.

Protective effects of hesperetin on the quality of sperm, apoptosis, lipid peroxidation, and oxidative stress during the process of cryopreservation: An experimental study.

BACKGROUND: Hesperetin is a bioflavonoid compound, largely used in Chinese traditional medicine and found plenty in citrus fruits. Hesperetin has beneficial effects against different diseases. The sperm cryopreservation process is a common method that is used in infertility laboratories. It has been reported that during the cryopreservation process, the quality of sperm is significantly reduced. OBJECTIVE: To investigate the effect of hesperetin on the quality of human spermatozoa during the cryopreservation process. MATERIALS AND METHODS: In this experimental study, 22 sperm sample of normozoospermia men who reffered to the infertility department of the Shariati Hospital (Tehran, Iran) Between October and November 2019 were collect and divided in to three groups as: 1) fresh, 2) control (frozen-thawed group without treatment), and 3) treatment group as frozen-thawed samples supplemented with 20 µM hesperetin. Motility, Viability, morphology, Apoptotic-like changes, intracellular H 2 O 2 , intracellular O2 - , and lipid peroxidation (LPO) was measured. RESULTS: Hesperetin treatment during the cryopreservation process of human sperm significantly improved the viability, motility, and morphology rates of the spermatozoa after frozen-thawed process in control group (p < 0.01). In addition, it significantly reduced the reactive oxygen species (ROS) level, LPO level and increased the percentage of viable sperm cells with intact plasma membrane (p < 0.01) after frozen-thawed process. CONCLUSION: Hesperetin can improve the quality of human sperm and also protect human sperm against reactive oxygen species, LPO, and apoptosis during the cryopreservation-thawing process.

Effect of sulforaphane on apoptosis, reactive oxygen species and lipids peroxidation of human sperm during cryopreservation.

Sperm cryopreservation is a common procedure to preserve viable sperm for an indefinite period. This procedure has numerous detrimental effects on sperm function due to increased generation of reactive oxygen species (ROS). During cryopreservation, while ROS increases, antioxidant enzymes level decreases. It has been shown that a relationship exist between lower antioxidant levels and infertility. l-Sulforaphane (SFN) is an isothiocyanate in cruciferous vegetables of the brassica class that has potent protective effects against oxidative stress. The purpose of the present study was to evaluate the effects of SFN supplementation during the freeze-thaw process on different parameters of human spermatozoa which can influence sperm fertilizing ability. Samples were collected from 25 healthy men and each sample was divided into three groups: fresh, control (untreated frozen/thawed samples) and treatment (treated frozen/thawed with SFN) groups. Sperm parameters, ROS production (using flow cytometry), plasma membrane integrity (using flow cytometry), Lipid peroxidation (using ELISA) were evaluated. Our results demonstrated that 5 µM SFN improved all parameters of sperm including viability (P < 0.001), motility, and morphology (P < 0.05) after the freeze-thaw process. Furthermore, SFN reduced the levels of intracellular hydrogen peroxide (P < 0.01) and superoxide anion (P < 0.05). Also, SFN significantly increased the percentage of viable sperm cells with the intact plasma membrane (P < 0.001) and decreased the level of lipid peroxidation after the freeze-thaw process (P < 0.01).Our findings showed that spermatozoa treatment with 5 µM SFN before the freeze-thaw process has protective effects against oxidative stress and could decrease the detrimental effects of this process on sperm quality.