Epididymis seleno-independent glutathione peroxidase 5 maintains sperm DNA integrity in mice

Chabory, Eléonore; Damon, Coralie; Lenoir, Alain; Kauselmann, Gary; Kern, Hedrun; Zevnik, Branko; Garrel, Catherine; Saez, Fabrice; Cadet, Rémi; Henry-Berger, Joëlle; Schoor, Michael; Gottwald, Ulrich; Habenicht, U.‐F.; Drevet, Joël R.; Vernet, Patrick

doi:10.1172/jci38940

Cited by 145 publications

(212 citation statements)

References 54 publications

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“…HPX15 could be protecting sperm cells directly, as indicated by its secretion into the spermathecal lumen and by the presence of peroxidase activity on sperm tails, or could play a role in maintaining the correct physiology of spermathecal cells. Close association of peroxidase with sperm cells is reminiscent of the mammalian system, in which glutathione peroxidase GPX5 is secreted within the epididymis lumen, the site of sperm storage and maturation in males, and is found associated with sperm cell membranes, in which it prevents DNA damage, lipid peroxidation, and premature activation of the sperm by ROS (30,31). Downstream effects on embryogenesis caused by fertilization by partially damaged sperm may also cause or contribute to the lower fertility of dsHPX15-injected females.…”

Section: Discussionmentioning

confidence: 99%

Mating activates the heme peroxidase HPX15 in the sperm storage organ to ensure fertility in Anopheles gambiae

Shaw

Teodori

Mitchell

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Anopheles gambiae mosquitoes are major African vectors of malaria, a disease that kills more than 600,000 people every year. Given the spread of insecticide resistance in natural mosquito populations, alternative vector control strategies aimed at reducing the reproductive success of mosquitoes are being promoted. Unlike many other insects, An. gambiae females mate a single time in their lives and must use sperm stored in the sperm storage organ, the spermatheca, to fertilize a lifetime's supply of eggs. Maintenance of sperm viability during storage is therefore crucial to the reproductive capacity of these mosquitoes. However, to date, no information is available on the factors and mechanisms ensuring sperm functionality in the spermatheca. Here we identify cellular components and molecular mechanisms used by An. gambiae females to maximize their fertility. Pathways of energy metabolism, cellular transport, and oxidative stress are strongly regulated by mating in the spermatheca. We identify the mating-induced heme peroxidase (HPX) 15 as an important factor in long-term fertility, and demonstrate that its function is required during multiple gonotrophic cycles. We find that HPX15 induction is regulated by sexually transferred 20-hydroxy-ecdysone (20E), a steroid hormone that is produced by the male accessory glands and transferred during copulation, and that expression of this peroxidase is mediated via the 20E nuclear receptor. To our knowledge, our findings provide the first evidence of the mechanisms regulating fertility in Anopheles, and identify HPX15 as a target for vector control.

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Section: Discussionmentioning

confidence: 99%

Mating activates the heme peroxidase HPX15 in the sperm storage organ to ensure fertility in Anopheles gambiae

Shaw

Teodori

Mitchell

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…28 When the latter was knocked out, the animals developed an age-related phenotype associated with the induction of oxidative DNA damage in the spermatozoa and the appearance of birth defects in the offspring. 29 In addition to such antioxidant enzymes, small molecular mass free radical scavengers are also generated in the male tract, and are major constituents of the antioxidant protection afforded to the spermatozoa by seminal plasma. The most important of these scavengers are vitamin C, uric acid, tryptophan, spermine and taurine.…”

Section: Lack Of Antioxidant Protectionmentioning

confidence: 99%

Apoptosis and DNA damage in human spermatozoa

Aitken¹,

Koppers²

2010

Asian J Androl

292

179

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DNA damage is frequently encountered in spermatozoa of subfertile males and is correlated with a range of adverse clinical outcomes including impaired fertilization, disrupted preimplantation embryonic development, increased rates of miscarriage and an enhanced risk of disease in the progeny. The etiology of DNA fragmentation in human spermatozoa is closely correlated with the appearance of oxidative base adducts and evidence of impaired spermiogenesis. We hypothesize that oxidative stress impedes spermiogenesis, resulting in the generation of spermatozoa with poorly remodelled chromatin. These defective cells have a tendency to default to an apoptotic pathway associated with motility loss, caspase activation, phosphatidylserine exteriorization and the activation of free radical generation by the mitochondria. The latter induces lipid peroxidation and oxidative DNA damage, which then leads to DNA fragmentation and cell death. The physical architecture of spermatozoa prevents any nucleases activated as a result of this apoptotic process from gaining access to the nuclear DNA and inducing its fragmentation. It is for this reason that a majority of the DNA damage encountered in human spermatozoa seems to be oxidative. Given the important role that oxidative stress seems to have in the etiology of DNA damage, there should be an important role for antioxidants in the treatment of this condition. If oxidative DNA damage in spermatozoa is providing a sensitive readout of systemic oxidative stress, the implications of these findings could stretch beyond our immediate goal of trying to minimize DNA damage in spermatozoa as a prelude to assisted conception therapy.

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“…GPx catalyzes the reduction of organic and inorganic hydroperoxides by acting as an electron donor. The GPx family consists of several proteins classified according to their sequence, substrate specificity, and subcellular localization (Chabory et al 2009). Several studies have demonstrated the importance of the GPx family during spermatogenesis and its relationship to male factor fertility (Schneider et al 2009).…”

Section: Resultsmentioning

confidence: 99%

Oxidative stress and antioxidant enzyme defence system in seminal plasma of common carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss) during spawning season

Shaliutina‐Kolešová¹,

Rui²,

Ashtiani³

et al. 2018

CZECH J ANIM SCI

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Shaliutina-Kolešová A., Rui N., Ashtiani S., Rodina M., Cosson J., Linhart O. (2018): Oxidative stress and antioxidant enzyme defence system in seminal plasma of common carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss) during spawning season. Czech J. Anim. Sci., 63, 78-84.Assessment of seminal oxidative stress indicators is emerging as a valuable prognostic tool in assisted reproductive technology. We investigated levels of oxidative stress caused by reactive oxygen species (ROS) and the antioxidant enzyme defence system comprising superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx) in seminal plasma (SP) of common carp Cyprinus carpio and rainbow trout Oncorhynchus mykiss over the course of the spawning season. Oxidation was determined in lipids and proteins by assessing thiobarbituric acid reactive species (TBARS) and the 2,4-dinitrophenylhydrazine carbonyl groups, respectively. Levels of SOD were assessed by the autoxidation of pyrogallol. Determination of GR and GPx was based on the rate of NADPH oxidation. We observed clear alterations in lipids and proteins over the course of the spawning season in both species. The highest levels of TBARS and CP were recorded late in the season. SOD was not significantly altered in either species. The activity of GR was higher in carp SP late in spawning compared to other times (P < 0.05), while in rainbow trout, GR significantly increased (24.13 ± 2.8 mU/mg protein) in mid-season. A significantly lower GPx activity (9.18 ± 1.32 mU/mg protein) was found in rainbow trout SP early in the spawning season, but no significant differences in GPx were observed over the course of the season in carp. These results provide further understanding of the role of fish SP antioxidants and present new data on the oxidant and antioxidant balance in SP during the spawning season that may be of value in the development of methods for artificial reproduction of teleost species.

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Epididymis seleno-independent glutathione peroxidase 5 maintains sperm DNA integrity in mice

Cited by 145 publications

References 54 publications

Mating activates the heme peroxidase HPX15 in the sperm storage organ to ensure fertility in Anopheles gambiae

Mating activates the heme peroxidase HPX15 in the sperm storage organ to ensure fertility in Anopheles gambiae

Apoptosis and DNA damage in human spermatozoa

Oxidative stress and antioxidant enzyme defence system in seminal plasma of common carp (Cyprinus carpio) and rainbow trout (Oncorhynchus mykiss) during spawning season

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