Cytotoxic Effects of 2-Bromopropane on Embryonic Development in Mouse Blastocysts

Chan, Wen‐Hsiung

doi:10.3390/ijms11020731

Cited by 11 publications

(11 citation statements)

References 42 publications

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“…Thus, our results indicate that 2-BP significantly inhibits the proliferation of mouse blastocysts, and this effect is blocked by resveratrol. In our preliminary HPLC study, the mice’s drinking water containing 20 μM 2-BP for 4 days had serum 2-BP levels of about 5.63 μM [37]. Our current experiments clearly confirm the injurious effects of 5–10 μM 2-BP.…”

Section: Resultssupporting

confidence: 73%

Resveratrol Protects against 2-Bromopropane-Induced Apoptosis and Disruption of Embryonic Development in Blastocysts

Chan¹

2011

IJMS

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2-Bromopropane (2-BP) is used as an alternative to ozone-depleting cleaning solvents. Previously, we reported that 2-BP has cytotoxic effects on mouse blastocysts and is associated with defects in subsequent development. In the present work, we show that 2-BP induces apoptosis in the inner cell mass of mouse blastocysts, and inhibits cell proliferation. Both effects are suppressed by resveratrol, a grape-derived phytoalexin with known antioxidant and anti-inflammatory properties. 2-BP-treated blastocysts displayed lower levels of implantation (compared to controls) when plated on culture dishes in vitro, and a reduced ability to proceed to later stages of embryonic development. Pretreatment with resveratrol prevented 2-BP-induced disruption of embryonic development, both in vitro and in vivo. Further investigation of these processes revealed that 2-BP directly promotes ROS generation, loss of mitochondrial membrane potential (MMP), and activation of caspase-3, whereas resveratrol effectively blocks 2-BP-induced ROS production and the accompanying apoptotic biochemical changes. Our results collectively imply that 2-BP triggers the mitochondrion-dependent apoptotic pathway via ROS generation, and the antioxidant activity of resveratrol prevents 2-BP-induced toxicity.

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Section: Resultssupporting

confidence: 73%

Resveratrol Protects against 2-Bromopropane-Induced Apoptosis and Disruption of Embryonic Development in Blastocysts

Chan¹

2011

IJMS

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“…It is tightly regulated: apoptotic processes clear redundant or abnormal cells during embryonic development [ 21 , 22 ], but are not seen at earlier (i.e., zygote to blastocyst) developmental stages [ 23 ]. Importantly, our group has shown that the induction of cell apoptosis by physical or chemical teratogens in early-stage embryos can negatively impact embryonic development [ 20 , 24 , 25 ]. However, excessive or unsuitable apoptosis triggered in early embryos can cause injury effects on pre- and post-implantation embryonic development [ 17 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Rhein Induces Oxidative Stress and Apoptosis in Mouse Blastocysts and Has Immunotoxic Effects during Embryonic Development

Huang

Chan

2017

IJMS

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Rhein, a glucoside chemical compound found in a traditional Chinese medicine derived from the roots of rhubarb, induces cell apoptosis and is considered to have high potential as an antitumor drug. Several previous studies showed that rhein can inhibit cell proliferation and trigger mitochondria-related or endoplasmic reticulum (ER) stress-dependent apoptotic processes. However, the side effects of rhein on pre- and post-implantation embryonic development remain unclear. Here, we show that rhein has cytotoxic effects on blastocyst-stage mouse embryos and induces oxidative stress and immunotoxicity in mouse fetuses. Blastocysts incubated with 5–20 μM rhein showed significant cell apoptosis, as well as decreases in their inner cell mass cell numbers and total cell numbers. An in vitro development assay showed that rhein affected the developmental potentials of both pre- and post-implantation embryos. Incubation of blastocysts with 5–20 μM rhein was associated with increased resorption of post-implantation embryos and decreased fetal weight in an embryo transfer assay. Importantly, in an in vivo model, intravenous injection of dams with rhein (1, 3, and 5 mg/kg body weight/day) for four days resulted in apoptosis of blastocyst-stage embryos, early embryonic developmental injury, and decreased fetal weight. Intravenous injection of dams with 5 mg/kg body weight/day rhein significantly increased the total reactive oxygen species (ROS) content of fetuses and the transcription levels of antioxidant proteins in fetal livers. Additional work showed that rhein induced apoptosis through ROS generation, and that prevention of apoptotic processes effectively rescued the rhein-induced injury effects on embryonic development. Finally, the transcription levels of the innate-immunity related genes, CXCL1, IL-1 β and IL-8, were down-regulated in the fetuses of dams that received intravenous injections of rhein. These results collectively show that rhein has the potential to induce embryonic cytotoxicity and induce oxidative stress and immunotoxicity during the development of mouse embryos.

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“…Recent experiments showed that 2-BP induces apoptosis and developmental injury in mouse blastocysts [ 26 ]. However, its effects on mouse oocyte maturation and precise regulatory mechanisms remain to be established.…”

Section: Resultsmentioning

confidence: 99%

“…, via exposure to a teratogen) leads to embryonic developmental injury [ 15 , 17 , 23 – 25 ]. Previous studies by our group demonstrated that 2-BP promotes cell apoptosis and developmental injury in blastocyst-stage embryos that develop from the zygote for four days [ 26 ]. However, the effects of 2-BP on early-stage embryogenesis, such as oocyte maturation, fertilization, and sequential embryo development from zygotes, are currently unclear.…”

Section: Introductionmentioning

confidence: 99%

Hazardous Apoptotic Effects of 2-Bromopropane on Maturation of Mouse Oocytes, Fertilization, and Fetal Development

Chan

2010

IJMS

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2-Bromopropane (2-BP) is used as an alternative to ozone-depleting cleaning solvents. Previously, we reported that 2-BP has cytotoxic effects on mouse blastocysts and is associated with defects in subsequent development. Here, we further investigate the effects of 2-BP on oocyte maturation and subsequent pre- and post-implantation development, both in vitro and in vivo. Notably, 2-BP induced a significant reduction in the rates of oocyte maturation, fertilization, and in vitro embryonic development. Treatment of oocytes with 2-BP during in vitro maturation (IVM) resulted in increased resorption of postimplantation embryos and decreased fetal weights. Experiments with a mouse model disclosed that consumption of drinking water containing 20 μM 2-BP led to decreased oocyte maturation in vivo and fertilization in vitro, as well as impairment of early embryonic development. Interestingly, pretreatment with a caspase-3-specific inhibitor effectively prevented 2-BP-triggered hazardous effects, suggesting that embryonic impairment by 2-BP occurs via a caspase-dependent apoptotic process. A study using embryonic stem cells as the assay model conclusively demonstrated that 2-BP induces cell death processes through apoptosis and not necrosis, and inhibits early embryo development in mouse embryonic stem cells. These results collectively confirm the hazardous effects of 2-BP on embryos derived from pretreated oocytes.

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Cytotoxic Effects of 2-Bromopropane on Embryonic Development in Mouse Blastocysts

Cited by 11 publications

References 42 publications

Resveratrol Protects against 2-Bromopropane-Induced Apoptosis and Disruption of Embryonic Development in Blastocysts

Resveratrol Protects against 2-Bromopropane-Induced Apoptosis and Disruption of Embryonic Development in Blastocysts

Rhein Induces Oxidative Stress and Apoptosis in Mouse Blastocysts and Has Immunotoxic Effects during Embryonic Development

Hazardous Apoptotic Effects of 2-Bromopropane on Maturation of Mouse Oocytes, Fertilization, and Fetal Development

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