Effects of Ferroptosis on Male Reproduction

Liu, Yang; Cao, Xin; He, Chen; Guo, Xinrui; Cai, Hui; Aierken, Aili; Hua, Jinlian; Peng, Sha

doi:10.3390/ijms23137139

Cited by 27 publications

(15 citation statements)

References 90 publications

(99 reference statements)

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“…The same type of outcome was observed in the context of arsenite-induced male reproductive toxicity, where testicular cell death was shown to depend on the mechanism of ferroptosis. Several male reproductive diseases are known to depend on the ferroptosis mechanism due to the deposition of iron or ROS in testis as well as the dependency of spermatogenesis on iron abundance [ 143 ]. In this case however, 6-month exposure to drinking water contaminated with arsenite as low as 5 mg/L was shown to underlie pathological changes in mouse testis (2.5 μM in the case of GC-2spd cells cultured in vitro).…”

Section: Poisons and Toxicantsmentioning

confidence: 99%

Bioinorganic Modulators of Ferroptosis: A Review of Recent Findings

Bartos

Sikora

2023

IJMS

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Ferroptosis was first reported as a separate modality of regulated cell death in 2008 and distinguished under its current name in 2012 after it was first induced with erastin. In the following decade, multiple other chemical agents were researched for their pro- or anti-ferroptotic properties. Complex organic structures with numerous aromatic moieties make up the majority of this list. This review fills a more overlooked niche by gathering, outlining and setting out conclusions regarding less prominent cases of ferroptosis induced by bioinorganic compounds and reported on within the last few years. The article contains a short summary of the application of bioinorganic chemicals based on gallium, several chalcogens, transition metals and elements known as human toxicants used for the purpose of evoking ferroptotic cell death in vitro or in vivo. These are used in the form of free ions, salts, chelates, gaseous and solid oxides or nanoparticles. Knowledge of how exactly these modulators promote or inhibit ferroptosis could be beneficial in the context of future therapies aimed against cancer or neurodegenerative diseases, respectively.

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Section: Poisons and Toxicantsmentioning

confidence: 99%

Bioinorganic Modulators of Ferroptosis: A Review of Recent Findings

Bartos

Sikora

2023

IJMS

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“…Free PUFAs can be ultimately converted to phosphatidylethanolamine (PE)-PUFAs-OOH by three important enzymes, ACSL4, lysophosphatidylcholine acyltransferase 3 (LPCAT3), and lipoxygenases (LOXs; Jiang et al, 2020 ). The formation of lipid peroxides involves the formation of AA-PE from phosphatidylethanolamine (PE), an essential component of cell membranes, and arachidonic acid (AA), a PUFA, catalyzed by ACSL4 and LPCAT3, which is then peroxidized by iron-dependent LOX to form AA- OH -PE, the major actuator of ferroptosis ( Protchenko et al, 2021 ; Liu et al, 2022 ), this is shown in Figure 4 . ACSL family made up of proteins on the endoplasmic reticulum and outer membrane, ACSLs are responsible for the formation of fatty acid acyl coenzyme a esters from free long-chain fatty acids.…”

Section: Excess Glutamate Accumulation Can Inhibit the Cystine/glutam...mentioning

confidence: 99%

The initiator of neuroexcitotoxicity and ferroptosis in ischemic stroke: Glutamate accumulation

Fan

Liu

et al. 2023

Front. Mol. Neurosci.

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Glutamate plays an important role in excitotoxicity and ferroptosis. Excitotoxicity occurs through over-stimulation of glutamate receptors, specifically NMDAR, while in the non-receptor-mediated pathway, high glutamate concentrations reduce cystine uptake by inhibiting the System Xc-, leading to intracellular glutathione depletion and resulting in ROS accumulation, which contributes to increased lipid peroxidation, mitochondrial damage, and ultimately ferroptosis. Oxidative stress appears to crosstalk between excitotoxicity and ferroptosis, and it is essential to maintain glutamate homeostasis and inhibit oxidative stress responses in vivo. As researchers work to develop natural compounds to further investigate the complex mechanisms and regulatory functions of ferroptosis and excitotoxicity, new avenues will be available for the effective treatment of ischaemic stroke. Therefore, this paper provides a review of the molecular mechanisms and treatment of glutamate-mediated excitotoxicity and ferroptosis.

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“…27 Acute ferroptosis can result in oxidative stress in the testes and oxidative damage to sperm DNA, ultimately leading to testicular disorders. 28 Previous studies have reported that DEHP can lead to lipid metabolism alterations 29 and ferroptosis in testes. 30,31 In this study, we performed lipidomics analysis and detected indicators related to the ferroptosis pathway in vivo and in vitro.…”

Section: Introductionmentioning

confidence: 99%

“…Lipid metabolism is essential for testicular development, and alterations in lipid metabolism are closely associated with testicular atrophy 27 . Acute ferroptosis can result in oxidative stress in the testes and oxidative damage to sperm DNA, ultimately leading to testicular disorders 28 . Previous studies have reported that DEHP can lead to lipid metabolism alterations 29 and ferroptosis in testes 30,31 …”

Section: Introductionmentioning

confidence: 99%

Di‐(2‐ethylhexyl) phthalate induces ferroptosis in prepubertal mouse testes via the lipid metabolism pathway

Wang,

Li,

Zheng

et al. 2023

Environmental Toxicology

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Di‐(2‐ethylhexyl) phthalate (DEHP), a widely used plasticizer, has been shown to cause reproductive toxicity, but the precise mechanism remains unclear. This study aimed to investigate the possible molecular mechanism of DEHP‐induced testicular damage. In vivo study, we administered different doses of DEHP (0, 250, and 500 mg/kg/day) to male C57BL/6 mice from 22 and 35 days after birth. We found that DEHP exposure induced histopathological alterations in prepubertal testes, and testicular lipidomics indicated notable alterations in lipid metabolism and significant enrichment of ferroptosis. Further tests showed that ferrous iron (Fe2+) and malondialdehyde (MDA) levels significantly increased after DEHP exposure. Western blotting revealed that DEHP exposure reduced glutathione peroxidase 4 (GPX4) expression, and elevated acyl coenzyme A synthetase long‐chain member 4 (ACSL4) and lysophosphatidylcholine acyltransferase 3 (LPCAT3) expression. The in vitro results were consistent with the in vivo results. When Leydig cells and Sertoli cells were treated with ferrostatin‐1 and monoethylhexyl phthalate (MEHP), MEHP‐induced increases in Fe2+ and MDA levels, accumulation of lipid reactive oxygen species, downregulation of GPX4, and upregulation of ACSL4 and LPCAT3 were reversed. Collectively, our findings suggested that aberrant lipid metabolism and ferroptosis may be involved in prepubertal DEHP exposure‐induced testicular damage.

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Effects of Ferroptosis on Male Reproduction

Cited by 27 publications

References 90 publications

Bioinorganic Modulators of Ferroptosis: A Review of Recent Findings

Bioinorganic Modulators of Ferroptosis: A Review of Recent Findings

The initiator of neuroexcitotoxicity and ferroptosis in ischemic stroke: Glutamate accumulation

Di‐(2‐ethylhexyl) phthalate induces ferroptosis in prepubertal mouse testes via the lipid metabolism pathway

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