Protective effects of resveratrol on ethanol-induced apoptosis in embryonic stem cells and disruption of embryonic development in mouse blastocysts

Huang, Lien‐Hung; Shiao, Nion-Heng; Hsuuw, Yan‐Der; Chan, Wen‐Hsiung

doi:10.1016/j.tox.2007.09.015

Cited by 66 publications

(57 citation statements)

References 76 publications

(76 reference statements)

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“…This is consistent with results obtained during a study in which stress response of embryos after resveratrol treatment was investigated. When apoptosis was induced by ethanol in mouse blastocysts, resveratrol had a protective effect on the embryos [33]. In addition, resveratrol-treated blastocysts were resistant to ethanol-induced apoptosis and showed lower expression of Caspase-3 and Caspase-9 when compared to non-treated embryos.…”

Section: Discussionmentioning

confidence: 92%

Effect of Resveratrol on the Development of Porcine Embryos Produced In Vitro

Lee

Wang

Chaille

et al. 2010

Journal of Reproduction and Development

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Abstract. The effects of resveratrol (a phytoalexin with a wide variety of pharmacological activities) on pig embryos produced by parthenogenesis and/or in vitro fertilization have been investigated. First, parthenogenetic embryos were generated and cultured in PZM-3 medium supplemented with various amounts of resveratrol (0, 0.05, 0.1, 0.5, 1.0 and 25 μM final concentrations). In the presence of 0.5 μM resveratrol a significantly higher percentage of parthenogenetic embryos reached the blastocyst stage by day 7 compared to non-treated control (43.5 ± 6.3% vs. 33.0 ± 5.4%; P<0.05). The total cell number of blastocysts also increased as a result of incubation with 0.5 μM resveratrol; the difference was statistically significant between treated and non-treated embryos on day 5 of culture (35.8 ± 0.9 vs. 32.1 ± 1.1; P<0.05). Resveratrol incubation affected the expression levels of apoptosis-related genes in parthenogenetic blastocysts: the level of Bax transcripts was similar but lower expression of Bcl-2 and Caspase-3 was observed in embryos treated with 0.5 μM resveratrol when compared to control blastocysts (P<0.05). The results of the TUNEL assay were similar in blastocysts developing with or without resveratrol supplementation. In addition, when embryos produced by in vitro fertilization were incubated with 0.5 μM resveratrol, the treatment led to higher frequencies of blastocyst formation (8.6% vs. 13.3%) and elevated total cell numbers (37.1 ± 2.4 vs. 43.2 ± 1.7) by the end of the 7-day culture period (P<0.05). The results indicate that 0.5 μM resveratrol during culture has a positive effect on early embryonic development of porcine embryos. Key words: Development, Embryo, Pig, Resveratrol (J. Reprod. Dev. 56: [330][331][332][333][334][335] 2010) mbryo culture is valuable in the study of preimplantation embryonic development and is indispensable for the in vitro production of transferable embryos. In spite of significant improvements in the culture conditions, the development of in vitro-produced embryos is still suboptimal [1]. Because the preimplantation embryo is extremely sensitive to environmental factors, deficiencies in culture conditions often lead to aberrant embryo development that manifest in lower frequency of blastocyst formation and lower cell numbers and can affect fetal as well as postnatal life [2]. Modifications in the culture system can potentially improve the development of the cultured embryos.Resveratrol (3,4',5-trihydroxystilbene) is a phytoalexin identified in more than 70 plant species including grapes, plums, and peanuts [3]. Its biological function is to protect the plant in case of a parasitic attack or environmental stress [4]. Originally, the search for plant-derived compounds with pharmacological properties identified resveratrol as a blocker of enzymes involved in arachidonate metabolism [5] and later, an inhibitor of partially purified kinases [6]. Based on its ability to block the cyclooxygenase COX-1 resveratrol was suggested to have anticancer properties and it was demo...

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Section: Discussionmentioning

confidence: 92%

Effect of Resveratrol on the Development of Porcine Embryos Produced In Vitro

Lee

Wang

Chaille

et al. 2010

Journal of Reproduction and Development

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“…Because of the strong therapeutic potential, clinical trials for resveratrol in human for various diseases are currently being conducted (http:// clinicaltrials.gov/ct2/results?termϭresveratrol). Prior studies have shown that resveratrol prevented ethanol-induced apoptosis in embryonic stem cells and ethanol-disrupted mouse blastocyst development (Huang et al, 2007) and also protected ethanol-induced apoptosis in fetal rhombencephalic neurons (Antonio and Druse, 2008). In a recent study, resveratrol was found to improve ethanol-induced cognitive deficits in a rodent model of FASD (Tiwari and Chopra, 2011).…”

Section: Introductionmentioning

confidence: 95%

Resveratrol Restores Nrf2 Level and Prevents Ethanol-Induced Toxic Effects in the Cerebellum of a Rodent Model of Fetal Alcohol Spectrum Disorders

Kumar

Singh²,

LaVoie³

et al. 2011

Mol Pharmacol

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In humans, ethanol exposure during pregnancy produces a wide range of abnormalities in infants collectively known as fetal alcohol spectrum disorders (FASD). Neuronal malformations in FASD manifest as postnatal behavioral and functional disturbances. The cerebellum is particularly sensitive to ethanol during development. In a rodent model of FASD, high doses of ethanol (blood ethanol concentration 80 mM) induces neuronal cell death in the cerebellum. However, information on potential agent(s) that may protect the cerebellum against the toxic effects of ethanol is lacking. Growing evidence suggests that a polyphenolic compound, resveratrol, has antioxidant and neuroprotective properties. Here we studied whether resveratrol (3,5,4Ј-trihydroxy-trans-stilbene), a phytoalexin found in red grapes and blueberries, protects the cerebellar granule neurons against ethanol-induced cell death. In the present study, we showed that administration of resveratrol (100 mg/kg) to postnatal day 7 rat pups prevents ethanol-induced apoptosis by scavenging reactive oxygen species in the external granule layer of the cerebellum and increases the survival of cerebellar granule cells. It restores ethanol-induced changes in the level of transcription factor nuclear factor-erythroid derived 2-like 2 (nfe2l2, also known as Nrf2) in the nucleus. This in turn retains the expression and activity of its downstream gene targets such as NADPH quinine oxidoreductase 1 and superoxide dismutase in cerebellum of ethanol-exposed pups. These studies indicate that resveratrol exhibits neuroprotective effects in cerebellum by acting at redox regulating proteins in a rodent model of FASD.

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“…A considerable body of literature has addressed the effects of ethanol in mouse and human ES and neural stem cells [26][27][28][29][30][31][32][33][34][35][36]. Long-term in vitro ethanol exposure as a model of binge drinking has been used to study the molecular aspects of FAS.…”

Section: Introductionmentioning

confidence: 99%

Ethanol Alters the Balance of Sox2, Oct4, and Nanog Expression in Distinct Subpopulations During Differentiation of Embryonic Stem Cells

Ogony

Malahias

Vadigepalli

et al. 2013

Stem Cells and Development

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The transcription factors Sox2, Oct4, and Nanog regulate within a narrow dose-range embryonic stem (ES) cell pluripotency and cell lineage commitment. Excess of Oct4 relative to Sox2 guides cells to mesoendoderm (ME), while abundance of Sox2 promotes neuroectoderm (NE) formation. Literature does not address whether ethanol interferes with these regulatory interactions during neural development. We hypothesized that ethanol exposure of ES cells in early differentiation causes an imbalance of Oct4 and Sox2 that diverts cells away from NE to ME lineage, consistent with the teratogenesis effects caused by prenatal alcohol exposure. Mouse ES cells were exposed to ethanol (0, 25, 50, and 100 mM) during retinoic acid (10 nM)-directed differentiation to NE for 0-6 days, and the expression of Sox2, Oct4, and Nanog was measured in single live cells by multiparametric flow cytometry, and the cellular phenotype was characterized by immunocytochemistry. Our data showed an ethanol dose-and time-dependent asymmetric modulation of Oct4 and Sox2 expression, as early as after 2 days of exposure. Single-cell analysis of the correlated expression of Sox2, Oct4, and Nanog revealed that ethanol promoted distinct subpopulations with a high Oct4/Sox2 ratio. Ethanol-exposed cells differentiated to fewer b-III tubulin-immunoreactive cells with an immature neuronal phenotype by 4 days. We interpret these data as suggesting that ethanol diverted cells in early differentiation from the NE fate toward the ME lineage. Our results provide a novel insight into the mode of ethanol action and opportunities for discovery of prenatal biomarkers at early stages.

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Protective effects of resveratrol on ethanol-induced apoptosis in embryonic stem cells and disruption of embryonic development in mouse blastocysts

Cited by 66 publications

References 76 publications

Effect of Resveratrol on the Development of Porcine Embryos Produced In Vitro

Effect of Resveratrol on the Development of Porcine Embryos Produced In Vitro

Resveratrol Restores Nrf2 Level and Prevents Ethanol-Induced Toxic Effects in the Cerebellum of a Rodent Model of Fetal Alcohol Spectrum Disorders

Ethanol Alters the Balance of Sox2, Oct4, and Nanog Expression in Distinct Subpopulations During Differentiation of Embryonic Stem Cells

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