Oxidative stress-induced DNA damage of mouse zygotes triggers G2/M checkpoint and phosphorylates Cdc25 and Cdc2

Zhang, Yuting; Qian, Diting; Li, Zhiling; Huang, Yue; Wu, Que; Ru, Gaizhen; Chen, Man; Wang, Bin

doi:10.1007/s12192-016-0693-5

Cited by 37 publications

(33 citation statements)

References 51 publications

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“…γ H2AX is an early indicator of DNA damage [31], and we previously suggested that γ H2AX plays an important role in both DDR [28] and SAC by contributing to the recruitment of both TTK and MAD2L1 to the kinetochore during metaphase [38]. Our results in this study (Figure 2) showed that oxidative stress-induced DNA damage existed in H 2 O 2 -treated zygotes, but not in control zygotes.…”

Section: Discussionsupporting

confidence: 49%

Oxidative Stress Delays Prometaphase/Metaphase of the First Cleavage in Mouse Zygotes via the MAD2L1‐Mediated Spindle Assembly Checkpoint

Huang

et al. 2017

Oxidative Medicine and Cellular Longevity

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In zygotes, DNA damage delays the first cleavage to enable repair. Our previous study found that 0.03 mM hydrogen peroxide (H2O2) was the minimum concentration required for induction of oxidative DNA damage in mouse zygotes and that this represented the most similar situation to the clinical phenomenon. In this study, we quantified the cleavage rates of cells in blastocysts at different developmental stages, followed by immunofluorescence to detect activation of γ-H2A histone family member X (a marker of DNA damage) in zygotes to confirm that oxidative DNA damage was induced in H2O2-treated zygotes. Monitoring H3S10P (phosphorylation of Ser10 on histone H3; a prometaphase/metaphase marker) levels at different hour postinsemination revealed that treatment of zygotes with 0.03 mM H2O2 resulted in a prometaphase/metaphase delay. Furthermore, immunofluorescence staining for mitotic arrest deficient 2-like 1 and the protein kinase TTK, components of the spindle assembly checkpoint (SAC), suggested that this delay possibly involved SAC activation. These studies of the relationships between oxidative stress and SAC can promote the success rate of in vitro fertilization.

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Section: Discussionsupporting

confidence: 49%

Oxidative Stress Delays Prometaphase/Metaphase of the First Cleavage in Mouse Zygotes via the MAD2L1‐Mediated Spindle Assembly Checkpoint

Huang

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…Our data presented that embryo formation rates at 24 h and 48 h were approximate, but more blastocysts with less apoptotic cells were in control group than 0.03 mM H 2 O 2 . The concurrent research found G2/M delay of zygotes in 0.03 mM H 2 O 2 group [ 29 ]. As is known human embryos at 4- to 8-cell and mouse embryos at 1- to 2-cell are undergoing ZGA (zygotic gene activation) phase, which is a key process of maternal to zygotic transition [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Response of Mouse Zygotes Treated with Mild Hydrogen Peroxide as a Model to Reveal Novel Mechanisms of Oxidative Stress‐Induced Injury in Early Embryos

Qian

Zhang

et al. 2016

Oxidative Medicine and Cellular Longevity

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Our study aimed to develop embryo models to evaluate the impact of oxidative stress on embryo development. Mouse zygotes, which stayed at G1 phase, were treated with prepared culture medium (containing 0.00, 0.01, 0.02, 0.03, 0.04, 0.05, or 0.1 mM hydrogen peroxide (H2O2)) for 30 min in experiment 1. The dose-effects of H2O2 on embryo development were investigated via comparisons of the formation rate at each stage (2- and 4-cell embryos and blastocysts). Experiment 2 was carried out to compare behaviors of embryos in a mild oxidative-stressed status (0.03 mM H2O2) with those in a control (0 mM H2O2). Reactive oxygen species (ROS) levels, variation of mitochondrial membrane potential (MMP), expression of γH2AX, and cell apoptosis rate of blastocyst were detected. We observed a dose-dependent decrease on cleavage and blastocyst rates. Besides, higher level of ROS, rapid reduction of MMP, and the appearance of γH2AX revealed that embryos are injured early in mild oxidative stress. Additionally, γH2AX may involve during DNA damage response in early embryos. And the apoptotic rate of blastocyst may significantly increase when DNA damage repair is inadequate. Most importantly, our research provides embryo models to study cell cycle regulation and DNA damage response under condition of different levels of oxidative stress.

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“…These sites of regulation, which include G1/S, intra-S and G2/M are involved in the response to DNA damage [6]. Zhang et al [7] showed that Ƴ H2AX, a marker of DNA damage, appears in H-treated sperm 2 or 2 (like OS models) and also embryos fertilized with these sperms have delay for the cleavage, which implies an arrest at the control points of the cell cycle, specifically, G2/M through ATM → Chk1 → Cdc25B/Cdc25c signaling pathway [7].…”

Section: Discussionmentioning

confidence: 99%

Seminal Volume as an Indirect Factor for Determining Success at in Vitro Fertilization

Sánchez¹

2017

OGIJ

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The semen volume is made up by the accessory glands (90%) and germinal cells (10%) (RB Mayer, 2015). Seminal plasma has enabling factors for sperm microenvironment (Aida Pujol, 2016), allowing among many other processes, sperm maturation (Yu-Wen Kuo, 2016).Objective: To analyze the correlation of seminal volume parameters with the outcome of fertilized oocytes. Material and methods:It is a prospective observational study, including 100 couples undergoing in vitro fertilization. The seminal sample was obtained by ejaculation and analyzed with WHO's 2010 criteria (Andrology laboratory procedures manual, 2010). Data encompassed seminal volumes and fertilized oocytes. Statistical analysis was made with Kolmogorov-Smirnov normalization, determining correlation of Pearson and significance of p ≤0.05. Results:The following parameters were registered: Seminal volume: 1.5-7.6 (average 2.7 ml), number of fertilized MII oocytes: 1-33 (average 10 oocytes). Pearson correlation of 0.737 (p= 0.002). By dividing groups of fertilized oocytes and seminal volumes by standard Kolmogorov we obtained significance with the number of fertilized eggs with 4.8 and 14 oocytes (p=0.001), and we also obtained significance with the seminal volume, ranging from 2 to 3.2ml (p=0.003).Discussion: Our study shows that it exists a prognostic relationship between the seminal volume and the number of fertilized eggs in an in vitro fertilization. A seminal volume ranging from 2 to 3.2ml has a better chance to produce adequate fertilization. Volumes lower than this values may reflect inadequate sperm formation and regulation and volumes greater may reflect other inflammatory conditions, such as infection (Jared M Bienek, 2016). Conclusion:Seminal volume reflects a healthy testicular function, producing spermatozoa capable of achieving good fertilization. Alterations on the seminal volume indicate inadequate conditions for the correct formation of spermatozoa, or increased inflammation molecules that damage the microenvironment.

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Oxidative stress-induced DNA damage of mouse zygotes triggers G2/M checkpoint and phosphorylates Cdc25 and Cdc2

Cited by 37 publications

References 51 publications

Oxidative Stress Delays Prometaphase/Metaphase of the First Cleavage in Mouse Zygotes via the MAD2L1‐Mediated Spindle Assembly Checkpoint

Oxidative Stress Delays Prometaphase/Metaphase of the First Cleavage in Mouse Zygotes via the MAD2L1‐Mediated Spindle Assembly Checkpoint

Response of Mouse Zygotes Treated with Mild Hydrogen Peroxide as a Model to Reveal Novel Mechanisms of Oxidative Stress‐Induced Injury in Early Embryos

Seminal Volume as an Indirect Factor for Determining Success at in Vitro Fertilization

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