Melatonin ameliorates ochratoxin A-induced oxidative stress and apoptosis in porcine oocytes

Lan, Mei; Zhang, Yu; Wan, Xiang; Pan, Meng-Hao; Xu, Yao; Sun, Shao‐Chen

doi:10.1016/j.envpol.2019.113374

Cited by 65 publications

(34 citation statements)

References 37 publications

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“…OTA induced a dose-dependent inhibitory effect on cumulus expansion and oocyte maturation. These data are in agreement with a previous study in porcine oocytes reporting that OTA disturbed cumulus and granulosa cell diffusion and proliferation (Lan et al 2019). OTA affected oocyte maturation only at micromolar concentrations.…”

Section: Discussionsupporting

confidence: 93%

“…Chi Square test: Comparisons OTA-exposed versus vehicle control (1%MeOH): not significant redox status allows the combined analysis of qualitative and quantitative parameters able to distinguish severe damage (loss of cell viability, expressed as reduced mitochondrial activity and ROS generation) from mild functional damage (oxidative stress expressed as an adverse boosting of mitochondrial membrane potential leading to increased intracellular ROS levels). In porcine oocytes, OTA treatment led to mitochondrial clustering (Lan et al (2019) rather than dispersion, as in our study, indicating possible age-related differences. Indeed, juvenile sheep oocytes have fewer developed cytoplasmic microfilament networks (Velilla et al 2005), necessary for mitochondrial migration, which could be more sensitive to the mycotoxin.…”

Section: Discussionsupporting

confidence: 77%

“…At the end of IVM, OTA was found to significantly reduce progression to the MII stage. This was demonstrated to be due to negative effects on spindle organization and chromosome alignment, possibly through the mitogen-activated protein kinase (MAPK) signalling pathway, that, from transcriptomic analysis, was found to be a major pathway affected by OTA (Lan et al 2019). To the best of our knowledge, no studies to date analyzed the effects of nanomolar OTA concentrations on oocyte maturation.…”

Section: Discussionmentioning

confidence: 99%

“…A subsequent comparative study between mouse and porcine oocytes confirmed a significant reduction of the maturation rate in vitro in both species, but porcine oocytes were more sensitive to OTA than mouse oocytes (Lu et al 2018). A recent study (Lan et al 2019), using high-throughput technologies, showed that OTA exposure altered the expression of multiple genes in oocytes, indicating its molecular effects on oocyte maturation. OTA adversely affected porcine oocyte polar body (PB) extrusion by delaying CDC2-mediated cell cycle progression, and also disrupted meiotic spindle formation by altering phosphorylated MAPK expression.…”

Section: Introductionmentioning

confidence: 93%

“…OTA adversely affected porcine oocyte polar body (PB) extrusion by delaying CDC2-mediated cell cycle progression, and also disrupted meiotic spindle formation by altering phosphorylated MAPK expression. RNA-seq screening demonstrated that an OTA-induced aberration of oocyte mitochondria distribution and oxidative phosphorylation defects, which then caused oxidative stress, followed by early apoptosis and autophagy (Lan et al 2019). Another multitechnological study using a mouse model (Jia et al 2019) recently showed that OTA decreased oocyte maturation and fertility by inducing oxidative stress and epigenetic changes.…”

Section: Introductionmentioning

confidence: 99%

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Ochratoxin A affects oocyte maturation and subsequent embryo developmental dynamics in the juvenile sheep model

et al. 2020

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The genotoxic and nephrotoxic mycotoxin Ochratoxin A (OTA) has also been reported to have adverse effects on oocyte maturation and embryo development. Previous studies on the effects of OTA on female fertility have used micromolar concentrations, but no information is available to date on effects in a more relevant nanomolar range. This study used a juvenile sheep model to evaluate the effects of oocyte exposure to low levels of OTA on maturation, fertilization, and embryo development. Further, it was investigated whether different mechanisms of action of OTA could be responsible for varying toxic effects at different levels of exposure. Cumulus-oocyte-complexes (COCs) were exposed to 10 μmol/L–0.1 nmol/L OTA during in vitro maturation and evaluated for cumulus viability, oocyte maturation, and bioenergetic/oxidative status. COCs were subjected to in vitro fertilization, embryo culture, and embryo quality assessment via morphology, viability, bioenergetic/oxidative status, and time-lapse monitoring. At micromolar concentrations, OTA induced cytotoxic effects, by reducing cumulus expansion and oocyte maturation. OTA altered temporospatial dynamics of zygote pronuclear formation and embryo morphokinetics. Blastocysts, even morphologically normal, were found to undergo collapse events, which were probably related to boosted blastocyst mitochondrial activity. At nanomolar concentrations, OTA did not affect COC morpho-functional parameters, but impaired oocyte ability to prevent polyspermy and increased blastocyst apoptosis. In conclusion, in the female germ cell, cytotoxic nonspecific effects characterize OTA-induced toxicity at high exposure levels, whereas fine tuning-mode effects, not associated with altered cell viability and integrity, characterize OTA toxic action at low levels.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Ochratoxin A affects oocyte maturation and subsequent embryo developmental dynamics in the juvenile sheep model

et al. 2020

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Taurine alleviates ochratoxin A‐induced pyroptosis in PK‐15 cells by inhibiting oxidative stress

Liu

et al. 2022

J Biochem & Molecular Tox

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Ochratoxin A (OTA) is one of the most harmful mycotoxins, which can cause multiple toxicological effects, especially nephrotoxicity in animals and humans. Taurine is an essential amino acid with various biological functions such as anti‐inflammatory and anti‐oxidation. However, the protective effect of taurine on OTA‐induced nephrotoxicity and pyroptosis had not been reported. Our results showed that OTA exposure induced cytotoxicity and oxidative stress in PK‐15 cells, including reactive oxygen species (ROS) accumulation, increased mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX‐2), and decreased mRNA levels of catalase (CAT), glutathione peroxidase 1 (GPx1), and glutathione peroxidase 4 (GPx4). In addition, OTA treatment induced pyroptosis by increasing the expressions of pyroptosis‐related proteins NLRP3, GSDMD, Caspase‐1 P20, ASC, Pro‐caspase‐1, and IL‐1β. Meanwhile, taurine could alleviate OTA‐induced pyroptosis and cytotoxicity, as well as reduce ROS level, COX‐2, and iNOS mRNA levels, and increase the mRNA levels of the antioxidant enzyme in PK‐15 cells. Taken together, taurine alleviated OTA‐induced pyroptosis in PK‐15 cells by inhibiting ROS generation and altering the activity of antioxidant enzymes, thereby attenuating its nephrotoxicity.

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Ochratoxin A induces human kidney tubular epithelial cell apoptosis through regulating lipid raft/PTEN/AKT signaling pathway

Song

Liu

Zhao

et al. 2021

Environmental Toxicology

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Ochratoxin A (OTA) is a fungal toxin that causes serious threat to human health. OTA could lead to the injury of various tissues, especially kidney injury. However, the toxic effects of OTA on human kidney tubular epithelial cell (HK‐2) and the possible mechanism remains poorly understood. This study was to investigate the toxic effects of OTA on HK‐2 and elucidate the molecular mechanism. HK‐2 cells were treated OTA to evaluate the effect of OTA on cell viability and apoptosis. OTA inhibited the growth of HK‐2 in a concentration‐dependent manner. With the concentration increased, OTA significantly lead to the apoptosis of HK‐2. OTA could increase the levels of reactive oxygen species (ROS) and Malondialdehyde (MDA). Superoxide dismutase (SOD) and glutathione (GSH) activities were decreased by OTA. Furthermore, OTA increased Caspase‐3 and Bax expression and decreased BCL2 expression. Compared to the control group, the expression of PTEN was increased and the expression of PI3K and AKT were decreased in OTA treated groups. In addition, we found OTA could disrupt the formation of lipid raft by attenuating sphingomyelin and cholesterol levels. In conclusion, our results indicated that OTA induces apoptosis in HK‐2 through regulating PTEN/AKT signaling pathway via disrupting lipid raft formation.

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Melatonin ameliorates ochratoxin A-induced oxidative stress and apoptosis in porcine oocytes

Cited by 65 publications

References 37 publications

Ochratoxin A affects oocyte maturation and subsequent embryo developmental dynamics in the juvenile sheep model

Ochratoxin A affects oocyte maturation and subsequent embryo developmental dynamics in the juvenile sheep model

Taurine alleviates ochratoxin A‐induced pyroptosis in PK‐15 cells by inhibiting oxidative stress

Ochratoxin A induces human kidney tubular epithelial cell apoptosis through regulating lipid raft/PTEN/AKT signaling pathway

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