多双内分泌干扰剂 改变雌激素受体β介导表观遗传调节,促进子宫内膜异位症
Research square
|September 15, 2025
概括
聚二-126 (PCB-126) 暴露通过激活AXL/ERβ/DNMT3A轴促进子宫内膜异位症. 这会破坏表观遗传调节和免疫反应,加剧病情及其相关的疼痛和不孕症.
科学领域:
- 生殖生物学和毒理学.
- 疾病的内分泌学和分子机制.
背景情况:
- 子宫内膜异位症是一种导致骨盆疼痛和不孕症的疾病,原因是子宫内膜细胞在子宫外生长.
- 内分泌干扰化学物质 (EDC) 与子宫内膜异位症有关,但机制尚不清楚.
- 多二-126 (PCB-126) 是一种EDC,与子宫内膜异位症有很强的关联.
研究的目的:
- 阐明PCB-126促进子宫内膜异位症进展的机制.
- 研究AXL受体氨酸激酶 (AXL) 和DNA甲基转移酶3A (DNMT3A) 在PCB-126诱导的子宫内膜异位症中的作用.
主要方法:
- 利用术术诱导的子宫内膜异位症和人类子宫内膜细胞系的小鼠模型.
- 对小鼠进行PCB-126和AXL抑制剂 (BMS-777607) 的治疗.
- 产生了子宫内膜特异性的Dnmt3a淘汰小鼠,以评估DNMT3A的作用.
- 在宫外病变上进行RNA测序,以分析基因表达变化.
主要成果:
- 暴露于PCB-126显著增加了小鼠宫外病变的生长.
- PCB-126激活了类固醇受体辅激剂-1 (SRC-1) 异形/矩阵金属蛋白酶-9 (MMP9) /雌激素受体-β (ERβ) 轴.
- AXL/增长停止特定6 (GAS6) 途径被PCB-126上调,增强了ERβ活性.
- 抑制AXL抑制了宫外病变的生长.
- PCB-126/ERβ轴增加了DNMT3A的表达,导致炎症和免疫失调.
结论:
- PCB-126通过AXL/ERβ/DNMT3A轴驱动子宫内膜异位症的进展.
- 这一途径破坏了以雌激素为媒介的表观遗传调节.
- PCB-126诱导与子宫内膜异位症相关的免疫炎症反应,加剧疾病.
更多相关视频
08:28Assessment of the Effects of Endocrine Disrupting Compounds on the Development of Vertebrate Neural Network Function Using Multi-electrode Arrays
Published on: April 26, 2018
6.4K
08:02Mouse Model of Surgically-induced Endometriosis by Auto-transplantation of Uterine Tissue
Published on: January 6, 2012
29.7K
相关概念视频
Oogenesis
69.1K
In human women, oogenesis produces one mature egg cell or ovum for every precursor cell that enters meiosis. This process differs in two unique ways from the equivalent procedure of spermatogenesis in males. First, meiotic divisions during oogenesis are asymmetric, meaning that a large oocyte (containing most of the cytoplasm) and minor polar body are produced as a result of meiosis I, and again following meiosis II. Since only oocytes will go on to form embryos if fertilized, this unequal...
69.1K
Hormonal Regulation of the Menstrual Cycle
1.5K
The ovarian cycle regulates endometrial changes throughout a single menstrual cycle via the coordinated action of gonadotrophin-releasing hormone (GnRH) and gonadotrophins.
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...
1.5K
Epigenetic Regulation
3.7K
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...
3.7K
Epigenetic Regulation
33.5K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.5K
Target Cell Response to Hormones
5.2K
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
5.2K
