Cannabinoid-Immunophilin Signaling During Pregnancy

描述（由申请人提供）：拟建研究的目的是利用小鼠作为动物模型，探索胚胎着床过程中内源性大麻素-亲免疫素信号传导。大麻素发挥广泛的影响，包括受精，胚胎发育和着床。我们的实验室研究表明，子宫内的anandamide水平在着床过程中受到严格调控，低水平有益，高水平有害。卵巢雌激素和孕激素的功能对着床和妊娠的建立至关重要，主要通过它们的认知核受体来实现。FKBP52是一种亲免疫蛋白，作为核类固醇受体的共同伴侣，是其正常功能所必需的。雌性Fkbp52缺失小鼠由于黄体酮受体功能受损导致着床失败而不育。通过多种方法，我们将探讨内源性大麻素信号是否与亲免疫素信号协同作用，使子宫接受着床，最终目的是确定anandamide指数是否作为子宫接受性的标志。大麻的广泛使用及其对生殖的已知不利影响使这项研究与女性健康问题高度相关。

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.