环胺减少基因转录活动和胚胎体外发育通过抑制NF-κB表达通过减少AcH4K12通过抑制NF-κB表达
Zhao-Bo Luo1, Liu-Hui Yang1, Sheng-Zhong Han1
1Department of Animal Science, College of Agriculture, Yanbian University, Yanji, Jilin, 133002, China.
Chemico-biological interactions
|November 19, 2023
概括
环胺 (CTX) 通过破坏DNA和改变基因组修饰,损害卵细胞成熟和早期胚胎发育. 补充LBH589可以恢复发育潜力并改善胚胎质量.
科学领域:
- 生殖生物学 生殖生物学
- 发展性毒理学 发展性毒理学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 环胺 (CTX) 是一种化学疗法药物,已知具有生殖毒性.
- CTX对卵细胞和卵巢产生负面影响,导致女性生殖功能障碍.
- CTX对早期胚胎发育和表观遗传修饰的影响需要进一步研究.
研究的目的:
- 研究CTX对猪卵细胞体外成熟 (IVM) 和随后的胚胎发育的影响.
- 检查CTX在胚胎早期发育过程中对表观遗传修饰,特别是基因素乙化 (AcH4K12) 的影响.
- 评估LBH589在抵消CTX诱导的发育缺陷方面的潜力.
主要方法:
- 在IVM期间,猪卵细胞被CTX处理.
- 在体外受精 (IVF) 后评估了胚胎发育.
- 分析了基因组基因修饰 (AcH4K12),DNA损伤,细胞亡和基因表达.
- 为了评估其保护作用,给予了LBH589.
主要成果:
- CTX 损害了卵细胞的成熟,导致线和线粒体异常,DNA 损伤和亡.
- CTX显著降低了猪胚胎发育能力,并诱导了胚芽细胞的DNA损伤和亡.
- 在早期胚胎中,CTX导致异常的AcH4K12基因素修饰,并降低了NF-κB蛋白表达.
- LBH589补充恢复了AcH4K12水平,增强了NF-κB表达,并改善了IVF胚胎的发育.
- LBH589减轻了CTX诱导的DNA损伤和亡,上调BCL2,POU5F1,SOX2和SOD1,同时降低BAX的调节.
结论:
- CTX诱导了表观遗传变化,特别是异常的AcH4K12基因组修饰,并减少了NF-κB表达,可能阻碍了囊细胞基因组激活 (ZGA).
- LBH589有效地抵消CTX诱导的损伤,恢复组织蛋白修饰,NF-κB水平,并改善早期胚胎发育潜力.
- 这些发现凸显了CTX对生殖表观遗传学的有害影响,并提供了使用LBH589.9的潜在治疗策略.
更多相关视频
10:26Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes
Published on: January 16, 2015
8.5K
13:38Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
Published on: January 18, 2017
12.3K
相关概念视频
NF-κB-dependent Signaling Pathway
7.5K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.5K
Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
Eukaryotic Transcription Inhibitors
9.8K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.8K
Teratogenicity
2.5K
The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
2.5K
In-vitro Mutagenesis
14.0K
To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
14.0K
