Evaluation of the NOX5 protein expression and oxidative stress in sperm from asthenozoospermic men compared to normozoospermic men

Vatannejad, Akram; Tavilani, Heidar; Sadeghi, Mohammad Reza; Karimi, Mehrdad; Lakpour, Niknam; Amanpour, Saeid; Nashtaei, Maryam Shabani; Doosti, Mahmood

doi:10.1007/s40618-019-01035-4

Cited by 26 publications

(19 citation statements)

References 55 publications

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“…Many species, not mouse, also possess an NADPH oxidase (NOX5) that is capable of generating ROS in a calcium-dependent manner. Overexpression of this enzyme has been linked to the loss of sperm motility observed in asthenozoospermia (Vatannejad et al 2019). The major product from all of these sources is O 2 −· which then dismutates to H 2 O 2 under the influence of superoxide dismutase (SOD).…”

Section: Sources Of Ros In Sperm -Amino Acid Oxidasementioning

confidence: 99%

“…So if NOX5 does, as proposed, play a central role in sperm biology, it is not a ubiquitous mechanism. Nevertheless, from a clinical perspective, asthenozoospermia has been associated with the over-expression of NOX5 compared with normozoospermic males, as well as significantly elevated levels of peroxynitrite, O 2 −· and hydrogen peroxide generation (Vignini et al 2006, Vatannejad et al 2019. In view of these data, a potential role for this oxidase in the pathogenesis of defective sperm function cannot be ruled out.…”

Section: Sources Of Ros In Sperm -Nadph Oxidase and Sperm Capacitationmentioning

confidence: 99%

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Impact of oxidative stress on male and female germ cells: implications for fertility

2020

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Male and female germ lines are vulnerable to oxidative stress. In spermatozoa, such stress triggers a lipid peroxidation cascade that culminates in the generation of electrophilic lipid aldehydes that bind to DNA and a raft of proteins involved in the delivery of functionally competent cells. One set of targets for these aldehydes are the proteins of the mitochondrial electron transport chain. When this interaction occurs, mitochondrial ROS generation is enhanced leading to the sustained generation of oxidative damage in a self-perpetuating cycle. Such damage affects all aspects of sperm function including motility, sperm-egg recognition, acrosomal exocytosis and sperm-oocyte fusion. Oxidative stress in the male germ line also attacks the integrity of sperm DNA with potential impacts on the developmental capacity of embryos and the health and wellbeing of the offspring. Potential pathways of reactive oxygen species (ROS) generation in male germ cells could involve enhanced lipoxygenase activity, activation of NADPH oxidase and/or electron leakage from mitochondria. Similarly, in the female germ line, both the induction of oocyte senescence following ovulation and the deterioration of oocyte quality with maternal age appear to involve the generation of oxidative damage. In this case, the mitochondria appear to be a particularly important source of ROS compromising the viability and fertilizability of the oocyte and interfering with the normal segregation of chromosomes during meiosis. In light of these considerations, antioxidants should have some role to play in the preservation of reproductive function in both men and women; however, we still await appropriate trials to test this hypothesis.

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Section: Sources Of Ros In Sperm -Amino Acid Oxidasementioning

confidence: 99%

Section: Sources Of Ros In Sperm -Nadph Oxidase and Sperm Capacitationmentioning

confidence: 99%

Impact of oxidative stress on male and female germ cells: implications for fertility

2020

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“…•− and H 2 O 2 , has been detected in the acrosome, neck, and tail of human spermatozoa [46,47]. Nitric oxide synthase and other non-enzymatic mechanisms have also been proposed to participate in the production of nitric oxide [48,49].…”

Section: Sources Of Ros In Spermatozoamentioning

confidence: 99%

Sperm Oxidative Stress during In Vitro Manipulation and Its Effects on Sperm Function and Embryo Development

et al. 2021

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Reactive oxygen species (ROS) generated at low levels during mitochondrial respiration have key roles in several signaling pathways. Oxidative stress (OS) arises when the generation of ROS exceeds the cell’s antioxidant scavenging ability and leads to cell damage. Physiological ROS production in spermatozoa regulates essential functional characteristics such as motility, capacitation, acrosome reaction, hyperactivation, and sperm-oocyte fusion. OS can have detrimental effects on sperm function through lipid peroxidation, protein damage, and DNA strand breakage, which can eventually affect the fertility of an individual. Substantial evidence in the literature indicates that spermatozoa experiencing OS during in vitro manipulation procedures in human- and animal-assisted reproduction are increasingly associated with iatrogenic ROS production and eventual impairment of sperm function. Although a direct association between sperm OS and human assisted reproductive techniques (ART) outcomes after in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) is still a matter of debate, studies in animal models provide enough evidence on the adverse effects of sperm OS in vitro and defective fertilization and embryo development. This review summarized the literature on sperm OS in vitro, its effects on functional ability and embryo development, and the approaches that have been proposed to reduce iatrogenic sperm damage and altered embryonic development.

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“…The clinical significance of NOX5 is indicated by its high level of expression in the spermatozoa of asthenozoospermic males in concert with increases in superoxide and hydrogen peroxide generation and DNA damage (157). NOX5 expression has also been shown to be elevated in cases of teratozoospermia (158).…”

Section: Nad(p)h Oxidasementioning

confidence: 99%

The Role of Genetics and Oxidative Stress in the Etiology of Male Infertility—A Unifying Hypothesis?

Aitken

Baker

2020

Front. Endocrinol.

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Despite the high prevalence of male infertility, very little is known about its etiology. In recent years however, advances in gene sequencing technology have enabled us to identify a large number of rare single point mutations responsible for impeding all aspects of male reproduction from its embryonic origins, through the endocrine regulation of spermatogenesis to germ cell differentiation and sperm function. Such monogenic mutations aside, the most common genetic causes of male infertility are aneuploidies such as Klinefelter syndrome and Y-chromosome mutations which together account for around 20-25% of all cases of non-obstructive azoospermia. Oxidative stress has also emerged as a major cause of male fertility with at least 40% of patients exhibiting some evidence of redox attack, resulting in high levels of lipid peroxidation and oxidative DNA damage in the form of 8-hydroxy-2'-deoxyguanosine (8OHdG). The latter is highly mutagenic and may contribute to de novo mutations in our species, 75% of which are known to occur in the male germ line. An examination of 8OHdG lesions in the human sperm genome has revealed ∼9,000 genomic regions vulnerable to oxidative attack in spermatozoa. While these oxidized bases are generally spread widely across the genome, a particular region on chromosome 15 appears to be a hot spot for oxidative attack. This locus maps to a genetic location which has linkages to male infertility, cancer, imprinting disorders and a variety of behavioral conditions (autism, bipolar disease, spontaneous schizophrenia) which have been linked to the age of the father at the moment of conception. We present a hypothesis whereby a number of environmental, lifestyle and clinical factors conspire to induce oxidative DNA damage in the male germ line which then triggers the formation de novo mutations which can have a major impact on the health of the offspring including their subsequent fertility.

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Evaluation of the NOX5 protein expression and oxidative stress in sperm from asthenozoospermic men compared to normozoospermic men

Cited by 26 publications

References 55 publications

Impact of oxidative stress on male and female germ cells: implications for fertility

Impact of oxidative stress on male and female germ cells: implications for fertility

Sperm Oxidative Stress during In Vitro Manipulation and Its Effects on Sperm Function and Embryo Development

The Role of Genetics and Oxidative Stress in the Etiology of Male Infertility—A Unifying Hypothesis?

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