Cannabinoid-Immunophilin Signaling During Pregnancy

怀孕期间的大麻素-免疫亲和素信号传导

• 批准号: 7151732
• 负责人: SUSANNE L TRANGUCH
• 金额: $ 3.14万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2007-10-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7151732
• 关键词: cannabinoids; endocannabinoids; peptidylprolyl isomerase; pregnancy; uterus

DESCRIPTION (provided by applicant): The objective of the proposed research is to explore endocannabinoid-immunophilin signaling during embryo implantation using mice as an animal model. Cannabinoids exert a broad array of effects, including fertilization, embryo development, and implantation. Our lab has shown that uterine anandamide levels are tightly regulated during implantation, with lower levels conducive and higher levels detrimental. Functions of ovarian estrogen and progesterone are essential to implantation and pregnancy establishment and executed primarily via their cognitive nuclear receptors. FKBP52, an immunophilin, functions as a co-chaperone for nuclear steroid receptors and is required for their normal functioning. Female Fkbp52 null mice are infertile because of implantation failure resulting from compromised progesterone receptor function. Using multiple approaches, we will explore whether endocannabinoid signaling collaborates with that of immunophilin in rendering the uterus receptive for implantation with the eventual goal of determining whether the anandamide index serves as a marker of uterine receptivity. Widespread marijuana use and its known adverse effects on reproduction classifies this research as highly relevant to women's health issues.

描述（由申请人提供）：拟议研究的目的是使用小鼠作为动物模型来探索胚胎植入过程中的内源性大麻素-免疫亲和素信号传导。大麻素具有广泛的作用，包括受精、胚胎发育和植入。我们的实验室表明，子宫 anandamide 水平在着床过程中受到严格调节，较低水平有利，较高水平有害。卵巢雌激素和孕激素的功能对于着床和妊娠的建立至关重要，并且主要通过其认知核受体来执行。 FKBP52 是一种亲免素，作为核类固醇受体的共伴侣，是其正常功能所必需的。雌性 Fkbp52 缺失小鼠因黄体酮受体功能受损导致着床失败而无法生育。我们将使用多种方法探索内源性大麻素信号传导是否与亲免素信号传导协同作用使子宫接受植入，最终目标是确定 anandamide 指数是否可以作为子宫接受性的标志。大麻的广泛使用及其已知的对生殖的不利影响使这项研究与女性健康问题高度相关。