雌激素受体α调节子宫上皮质谱系的规范性和恒常性
Jason A Rizo1, Kimberly M Davenport1, Wipawee Winuthayanon2
1Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA.
iScience
|August 25, 2023
概括
雌激素受体1 (ESR1) 对于正常的子宫发育至关重要. 在小鼠中ESR1的丧失导致异常的子宫上皮细胞分化,突出其在维持子宫平衡中的作用.
科学领域:
- 生殖生物学 生殖生物学
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
背景情况:
- 子宫上皮细胞的发育是一个复杂的过程,涉及肌体和上皮细胞之间的相互作用.
- 内在的转录因子和基因调控网络也控制了这种特征.
- 雌激素受体1 (ESR1) 是雌激素信号的关键媒介,在女性生殖道的发育和功能中起着至关重要的作用.
研究的目的:
- 研究雌激素受体1 (ESR1) 在子宫表皮的产后发育和分化中的作用.
- 为了确定ESR1如何影响子宫中的树皮-上皮相互作用.
- 阐明ESR1调节子宫上皮质谱系可塑性和恒常性的机制.
主要方法:
- 利用了小鼠遗传模型,对Esr1基因进行了有针对性的删除.
- 来自野生型和Esr1-null小鼠的确立和分析的子宫内膜上皮器官器官 (EEO).
- 在不同的条件下进行了有机体-体共同培养实验,包括雌激素治疗.
主要成果:
- 野生类型的有机体形成了一个正常的单层柱状上皮质.
- Esr1-null有机体表现出异常的发展,形成具有基底细胞的多层分层状上皮质.
- 与野生型 stromal 纤维细胞共同培养部分挽救了 Esr1-null 表皮中的基底细胞表型.
- 雌激素治疗和体内Esr1缺失增加了基底上皮细胞标记物.
结论:
- 雌激素受体1 (ESR1) 对于调节子宫上皮质谱系的可塑性和维持组织平衡至关重要.
- 失去ESR1促进了从光线向基底上皮质细胞类型的分化转变.
- 通过ESR1介导的膜信号传递是防止子宫表皮异常分化至关重要的.
相关概念视频
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
01:30Hormonal Control of the Ovarian Cycle
568
The ovarian cycle is meticulously regulated by the hypothalamic-pituitary-gonadal axis. This cycle orchestrates the release of a mature oocyte, essential for reproduction.
Before puberty, the hypothalamus releases GnRH in a low frequency, low amplitude pulsatile manner. This along with the immature hypothalamic-pituitary-gonadal axis activity, results in low estrogen levels and the absence of a fully functional ovarian cycle. At puberty, GnRH secretion increases in both frequency and...
Before puberty, the hypothalamus releases GnRH in a low frequency, low amplitude pulsatile manner. This along with the immature hypothalamic-pituitary-gonadal axis activity, results in low estrogen levels and the absence of a fully functional ovarian cycle. At puberty, GnRH secretion increases in both frequency and...
568
01:22Hormonal Regulation of the Menstrual Cycle
438
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...
438
01:31Transducer Mechanism: Nuclear Receptors
1.4K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.4K
01:20Proliferative Phase
533
The proliferative phase typically occurs after menstruation and lasts between 6 to 13 days in a standard 28-day cycle. This phase involves the reconstruction of the endometrium, guided by estrogen produced by the developing ovarian follicle.
Notably, the stratum basale, the basal layer of the endometrium, including the basal parts of the uterine glands, remains unaffected by menstruation. Stem cells in this layer undergo mitosis, regenerating the stratum functionalis and thickening the...
Notably, the stratum basale, the basal layer of the endometrium, including the basal parts of the uterine glands, remains unaffected by menstruation. Stem cells in this layer undergo mitosis, regenerating the stratum functionalis and thickening the...
533
01:15Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K