Are sperm capacitation and apoptosis the opposite ends of a continuum driven by oxidative stress?

Aitken, R. John; Baker, Mark A.; Nixon, Brett

doi:10.4103/1008-682x.153850

Cited by 153 publications

(115 citation statements)

References 73 publications

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“…An alternative source or ROS in mammalian spermatozoa might be the L‐Amino acid oxidase present in the spermatozoa of bulls (Tosic & Walton, ), horses (Aitken, Baker, & Nixon, ) rams (Upreti et al, ), and humans (Houston, Curry, & Aitken, ). This enzyme is involved in the oxidative deamination of aromatic amino acids, such as phenylalanine, tyrosine, and tryptophan.…”

Section: Physiological Sources Of Ros In Spermatozoamentioning

confidence: 99%

Reactive oxygen species as mediators of sperm capacitation and pathological damage

Aitken

2017

Molecular Reproduction Devel

453

370

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Oxidative stress plays a major role in the life and death of mammalian spermatozoa.These gametes are professional generators of reactive oxygen species (ROS), which appear to derive from three potential sources: sperm mitochondria, cytosolic L-amino acid oxidases, and plasma membrane Nicotinamide adenine dinucleotide phosphate oxidases. The oxidative stress created via these sources appears to play a significant role in driving the physiological changes associated with sperm capacitation through the stimulation of a cyclic adenosine monophosphate/Protein kinase A phosphorylation cascade, including the activation of Extracellular signal regulated kinase-like proteins, massive up-regulation of tyrosine phosphorylation in the sperm tail, as well as the induction of sterol oxidation. When generated in excess, however, ROS can induce lipid peroxidation that, in turn, disrupts membrane characteristics that are critical for the maintenance of sperm function, including the capacity to fertilize an egg.Furthermore, the lipid aldehydes generated as a consequence of lipid peroxidation bind to proteins in the mitochondrial electron transport chain, triggering yet more ROS generation in a self-perpetuating cycle. The high levels of oxidative stress created as a result of this process ultimately damage the DNA in the sperm nucleus; indeed, DNA damage in the male germ line appears to be predominantly induced oxidatively, reflecting the vulnerability of these cells to such stress. Extensive evaluation of antioxidants that protect the spermatozoa against oxidative stress while permitting the normal reduction-oxidation regulation of sperm capacitation is therefore currently being undertaken, and has already proven efficacious in animal models. | INTRODUCTIONCapacitation is a key feature of mammalian sperm cell biology, and was independently reported by Chang (1951) and Austin (1951); its discovery was a sentinel for unwrapping the mysteries of mammalian fertilization.Completion of capacitation provides sperm with a series of behaviours that are essential for the achievement of fertilization, including hyperactivated motility, sperm-zona pellucida recognition, and acrosome exocytosis. Despite being aware of capacitation for more than half a century, the molecular mechanisms that underpin this process at a physiological level are still far from resolved (Aitken & Nixon, 2013). We do know that capacitation involves an efflux of cholesterol from the sperm plasma membrane (Davis, 1981) and a global increase in tyrosine phosphorylation (Visconti et al., 1995). Yet, our understanding of how these elements are controlled is still quite embryonic. In this context, one insight that has emerged in the relatively recent past is that sperm capacitation is a reduction-oxidation (redox)-regulated event, promoted by the de novo generation of low levels of reactive oxygen species (ROS). One of the first scientists to discover this association was the late Claude Gagnon, who published an important paper in 1993 citing the ability of superoxide to...

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Section: Physiological Sources Of Ros In Spermatozoamentioning

confidence: 99%

Reactive oxygen species as mediators of sperm capacitation and pathological damage

Aitken

2017

Molecular Reproduction Devel

453

370

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“…Oxidative stress and apoptosis also play a key role during spermatogenesis (Aitken et al , 2015; Dias et al , 2013; Oliveira et al , 2015b). mTOR inhibition was shown to alleviate the levels of ROS induced by acrolein, to protect mitochondrial membrane and to increase the Bcl2/Bax ratio in mice male germ cells, illustrating a protection against apoptosis and an involvement in mitochondrial function in these cells (Webber et al , 2014).…”

Section: Discussionmentioning

confidence: 99%

Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

Jesus

Oliveira

Sousa

et al. 2017

Critical Reviews in Biochemistry and Molecular Biology

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Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolic phenotype and is involved in virtually all aspects of cellular function. It integrates not only nutrient and energy-sensing pathways but also actin cytoskeleton organization, in response to environmental cues including growth factors and cellular energy levels. These events are pivotal for spermato-genesis and determine the reproductive potential of males. Yet, the molecular mechanisms by which mTOR signaling acts in male reproductive system remain a matter of debate. Here, we review the current knowledge on physiological and molecular events mediated by mTOR in testis and testicular cells. In recent years, mTOR inhibition has been explored as a prime strategy to develop novel therapeutic approaches to treat cancer, cardiovascular disease, autoimmunity, and metabolic disorders. However, the physiological consequences of mTOR dysregulation and inhibition to male reproductive potential are still not fully understood. Compelling evidence suggests that mTOR is an arising regulator of male fertility and better understanding of this atypical protein kinase coordinated action in testis will provide insightful information concerning its biological significance in other tissues/organs. We also discuss why a new generation of mTOR inhibitors aiming to be used in clinical practice may also need to include an integrative view on the effects in male reproductive system.

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“…In particular, the generation of reactive oxygen species (ROS), particularly peroxynitrite, which takes place during capacitation, could facilitate the removal of cholesterol from PM [21], thus increasing its fluidity, cause a change in the pattern of protein tyrosine phosphorylation and increase the cAMP production [22,23]. If the fertilization does not occur, the accumulation of ROS could activate the apoptosis via the intrinsic pathway [24].…”

Section: Spermatozoa Membrane Dynamicsmentioning

confidence: 99%

Membrane Dynamics of Spermatozoa during Capacitation: New Insight in Germ Cells Signalling

Bernabò¹,

Ramal-Sanchez²,

Valbonetti³

et al. 2018

Germ Cell

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The study of germline stem cells and of germline cells has deep implications for the understanding of fertility, development and cancer. Nowadays, we are experiencing the very fascinating challenge of application of -OMICS technologies to this issue, which is opening new and unexpected horizons in virtually all the branches of biology. Here, we carried out a review of signalling systems involved in maturation of male germ cells and in the process that leads them to become fully fertile. In particular, we discuss the control mechanisms involved in capacitation and acrosome reaction that act at membrane level. Indeed, spermatozoa membranes play key roles in determining the achievement of fertility: they are the interface with the surrounding environment, they locate the signal transduction systems and they are active in recognizing and binding the oocyte. In addition, we discuss the effect of several compounds that could exert a negative effect on reproductive activity, by interfering with the endocrine axis, the so-called endocrine disruptors.

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Are sperm capacitation and apoptosis the opposite ends of a continuum driven by oxidative stress?

Cited by 153 publications

References 73 publications

Reactive oxygen species as mediators of sperm capacitation and pathological damage

Reactive oxygen species as mediators of sperm capacitation and pathological damage

Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

Membrane Dynamics of Spermatozoa during Capacitation: New Insight in Germ Cells Signalling

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