Relationship between functional Nrf2 gene promoter polymorphism and sperm DNA damage in male infertility

Aydos, Oya Sena; Yükselten, Yunus; Aydos, Dunya; Sunguroğlu, Asuman; Aydos, Kaan

doi:10.1080/19396368.2021.1972359

Cited by 12 publications

(9 citation statements)

References 75 publications

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“…The nuclear factor-erythroid 2-related factor 2 (Nrf2) is a crucial transcription factor in the cellular antioxidant defence since it promotes the expression of several antioxidant enzymes and allows the production of reduced GSH by increasing levels of enzymes involved in its production (Wild & Mulcahy 2000, Nguyen et al 2003. Mutations in the Nrf2 promoter are associated with sperm DNA damage in infertile men (Aydos et al 2021). Moreover, Nrf2 knockout males have reduced fertility with increased oxidative stress and sperm DNA damage (Nakamura et al 2010).…”

Section: Oxidative Stress and Male Infertilitymentioning

confidence: 99%

OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: The protection of mammalian spermatozoa against oxidative stress

O’Flaherty

Scarlata

2022

Reproduction

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The spermatozoon is very sensitive to high reactive oxygen species (ROS) levels due to its limited antioxidant system. A consortium of antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidases (GPXs), peroxiredoxins (PRDXs), thioredoxins, and glutathione-S-transferases is necessary to produce healthy spermatozoa and to maintain sperm quality to ensure motility, capacitation and DNA integrity. A delicate balance between ROS production and antioxidant enzymes is needed to ensure ROS-dependent sperm capacitation. GPX4 is an essential component of the mitochondrial sheath in mammalian spermatozoa, and GPX5 is a crucial antioxidant defence in the mouse epididymis to protect the sperm genome during the maturation of the spermatozoon. The mitochondrial superoxide (O2•-) production is controlled by SOD2, and the hydrogen peroxide (H2O2) generated by SOD2 activity and peroxynitrite (ONOO-) are scavenged mainly by PRDXs in human spermatozoa. PRDXs regulate the redox signalling necessary for sperm motility and capacitation, particularly by PRDX6. This enzyme is the first line of defence against oxidative stress to prevent lipid peroxidation and DNA oxidation by scavenging H2O2 and ONOO- through its peroxidase activity and repairing oxidized membranes by its calcium-independent phospholipase A2 activity. The success of antioxidant therapy in treating infertility resides in the proper diagnosis of the presence of oxidative stress and which type of ROS are produced. Thus, more research on the molecular mechanisms affected by oxidative stress, the development of novel diagnostic tools to identify infertile patients with oxidative stress, and randomized controlled trials are of paramount importance to generate personalized antioxidant therapy to restore male fertility.

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Section: Oxidative Stress and Male Infertilitymentioning

confidence: 99%

OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: The protection of mammalian spermatozoa against oxidative stress

O’Flaherty

Scarlata

2022

Reproduction

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“…However, if Nrf2 activity is impaired, oxidative stress and inflammation accumulate. Additionally, Nrf2 regulates cellular resistance to oxidative stress in the testis, which affects the physiology and pathology of testicular issues, particularly the spermatogenic process [ [15] , [16] , [17] , 52 ]. It has been proposed that Nrf2 expression is necessary for proper spermatogenesis and sperm-specific processes, including motility.…”

Section: Discussionmentioning

confidence: 99%

“…Nrf2 is a significant protein that helps defend our body against oxidative stress by activating genes to protect against ROS; this regulates cellular resistance to oxidative stress in the testis and affects spermatogenesis. Proper Nrf2 expression is necessary for adequate spermatogenesis and sperm-specific processes, including motility [ [15] , [16] , [17] ].…”

Section: Introductionmentioning

confidence: 99%

Oral administration of proniosomal glibenclamide formulation protects testicular tissue from hyperglycemia fluctuations and ROS via Nrf2/HO-1 pathway

Alyami,

Alnakhli,

Alshiban

et al. 2024

Heliyon

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“…By enhancing the NRF2 activity and the expression of antioxidant proteins, L-Carnitine contributes to the protection of cells against OS and promotes overall cellular health. Additionally, Nrf2 activation may enhance the expression of genes involved in spermatogenesis, sperm motility, and DNA repair, further contributing to male reproductive health [ 80 , 81 ].…”

Section: Signaling Pathways Affected By L-carnitinementioning

confidence: 99%

L-Carnitine and Male Fertility: Is Supplementation Beneficial?

Mateus,

Moreira,

Martins

et al. 2023

JCM

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L-Carnitine, a natural antioxidant found in mammals, plays a crucial role in the transport of long-chain fatty acids across the inner mitochondrial membrane. It is used as a nutritional supplement by professional athletes, improving performance and post-exercise recovery. Additionally, its therapeutic applications, including those in male infertility, have been investigated, as it may act as a defense mechanism against the excessive production of reactive oxygen species (ROS) in the testis, a process that can lead to sperm damage. This effect is achieved by enhancing the expression and activity of enzymes with antioxidant properties. Nevertheless, the mechanisms underlying the benefits of L-Carnitine remain unknown. This review aims to consolidate the current knowledge about the potential benefits of L-Carnitine and its role in male (in)fertility. Considering in vitro studies with Sertoli cells, pre-clinical studies, and investigations involving infertile men, a comprehensive understanding of the effects of L-Carnitine has been established. In vitro studies suggest that L-Carnitine has a direct influence on somatic Sertoli cells, improving the development of germ cells. Overall, evidence supports that L-Carnitine can positively impact male fertility, even at a relatively low dose of 2 g/day. This supplementation enhances sperm parameters, regulates hormone levels, reduces ROS levels, and subsequently improves fertility rates. However, further research is needed to elucidate the underlying mechanisms and establish optimal doses. In conclusion, the role of L-Carnitine in the field of male reproductive health is highlighted, with the potential to improve sperm quality and fertility.

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Relationship between functional Nrf2 gene promoter polymorphism and sperm DNA damage in male infertility

Cited by 12 publications

References 75 publications

OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: The protection of mammalian spermatozoa against oxidative stress

OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: The protection of mammalian spermatozoa against oxidative stress

Oral administration of proniosomal glibenclamide formulation protects testicular tissue from hyperglycemia fluctuations and ROS via Nrf2/HO-1 pathway

L-Carnitine and Male Fertility: Is Supplementation Beneficial?

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