Human spermatozoa possess an IL4I1 l-amino acid oxidase with a potential role in sperm function

Houston, Brendan J; Curry, Benjamin J.; Aitken, R. John

doi:10.1530/rep-14-0621

Cited by 42 publications

(27 citation statements)

References 46 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, 1950), horses (Aitken, Naumovski, et al, 2015) rams (Upreti et al, 1998), and humans (Houston, Curry, & Aitken, 2015). 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

476

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

476

370

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“…A similar situation has been observed in ram [70] and stallion [71] spermatozoa. While human spermatozoa also contain an aromatic amino acid oxidase, it is not bound and becomes rapidly lost from cells if their plasma membrane integrity has been compromised [72]. One of the obvious solutions to this amino acid oxidase problem in domestic animals has been to incorporate catalase into the sperm cryopreservation medium [73].…”

Section: Cryostoragementioning

confidence: 99%

The Importance of Oxidative Stress in Determining the Functionality of Mammalian Spermatozoa: A Two-Edged Sword

2020

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This article addresses the importance of oxidative processes in both the generation of functional gametes and the aetiology of defective sperm function. Functionally, sperm capacitation is recognized as a redox-regulated process, wherein a low level of reactive oxygen species (ROS) generation is intimately involved in driving such events as the stimulation of tyrosine phosphorylation, the facilitation of cholesterol efflux and the promotion of cAMP generation. However, the continuous generation of ROS ultimately creates problems for spermatozoa because their unique physical architecture and unusual biochemical composition means that they are vulnerable to oxidative stress. As a consequence, they are heavily dependent on the antioxidant protection afforded by the fluids in the male and female reproductive tracts and, during the precarious process of insemination, seminal plasma. If this antioxidant protection should be compromised for any reason, then the spermatozoa experience pathological oxidative damage. In addition, situations may prevail that cause the spermatozoa to become exposed to high levels of ROS emanating either from other cells in the immediate vicinity (particularly neutrophils) or from the spermatozoa themselves. The environmental and lifestyle factors that promote ROS generation by the spermatozoa are reviewed in this article, as are the techniques that might be used in a diagnostic context to identify patients whose reproductive capacity is under oxidative threat. Understanding the strengths and weaknesses of ROS-monitoring methodologies is critical if we are to effectively identify those patients for whom treatment with antioxidants might be considered a rational management strategy.

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“…In the sea urchin, fucose sulfate glycoconjugates and polymers, components of the egg jelly coat, were shown to play a role in stimulating the AR ( Decker et al ., 1976 ; Mengerink et al ., 2000 ). Molecular characterization of acrosome reaction-inducing substance recently confirmed the role of this highly sulfated glycoprotein as an AR-inducing substance in starfish ( Hoshi et al ., 2012 ).…”

Section: Sperm Activationmentioning

confidence: 81%

Gamete activation: basic knowledge and clinical applications

Tosti

Ménézo²

2016

Hum. Reprod. Update

111

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BackgroundThe first clues to the process of gamete activation date back to nearly 60 years ago. The mutual activation of gametes is a crucial event during fertilization. In the testis and ovaries, spermatozoa and oocytes are in a state of meiotic and metabolic quiescence and require reciprocal signals in order to undergo functional changes that lead to competence for fertilization. First, the oocyte activates sperm by triggering motility, chemoattraction, binding and the acrosome reaction, culminating with the fusion of the two plasma membranes. At the end of this cascade of events, collectively known as sperm capacitation, sperm-induced oocyte activation occurs, generating electrical, morphological and metabolic modifications in the oocyte.Objective and rationaleThe aim of this review is to provide the current state of knowledge regarding the entire process of gamete activation in selected specific animal models that have contributed to our understanding of fertilization in mammals, including humans. Here we describe in detail the reciprocal induction of the two activation processes, the molecules involved and the mechanisms of cell interaction and signal transduction that ultimately result in successful embryo development and creation of a new individual.Search methodsWe carried out a literature survey with no restrictions on publication date (from the early 1950s to March 2016) using PubMed/Medline, Google Scholar and Web of Knowledge by utilizing common keywords applied in the field of fertilization and embryo development. We also screened the complete list of references published in the most recent research articles and relevant reviews published in English (both animal and human studies) on the topics investigated.OutcomesLiterature on the principal animal models demonstrates that gamete activation is a pre-requisite for successful fertilization, and is a process common to all species studied to date. We provide a detailed description of the dramatic changes in gamete morphology and behavior, the regulatory molecules triggering gamete activation and the intracellular ions and second messengers involved in active metabolic pathways in different species. Recent scientific advances suggest that artificial gamete activation may represent a novel technique to improve human IVF outcomes, but this approach requires caution.Wider implicationsAlthough controversial, manipulation of gamete activation represents a promising tool for ameliorating the fertilization rate in assisted reproductive technologies. A better knowledge of mechanisms that transform the quiescent oocyte into a pluripotent cell may also provide new insights for the clinical use of stem cells.

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Human spermatozoa possess an IL4I1 l-amino acid oxidase with a potential role in sperm function

Cited by 42 publications

References 46 publications

Reactive oxygen species as mediators of sperm capacitation and pathological damage

Reactive oxygen species as mediators of sperm capacitation and pathological damage

The Importance of Oxidative Stress in Determining the Functionality of Mammalian Spermatozoa: A Two-Edged Sword

Gamete activation: basic knowledge and clinical applications

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