Cannabinoid-Immunophilin Signaling During Pregnancy

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探索胚胎植入期间的内源性大麻素-亲免素信号传导。大麻素发挥广泛的影响，包括受精，胚胎发育和植入。我们的实验室已经表明，子宫anandamide水平在植入过程中受到严格调节，较低的水平有益，较高的水平有害。卵巢雌激素和孕激素的功能对着床和妊娠建立至关重要，主要通过其认知核受体执行。FKBP 52是一种亲免蛋白，作为核类固醇受体的共伴侣，是其正常功能所必需的。雌性Fkbp 52缺失小鼠由于孕酮受体功能受损导致的着床失败而不育。使用多种方法，我们将探讨内源性大麻素信号传导是否与亲免素信号传导合作，使子宫易于植入，最终目标是确定大麻素指数是否可作为子宫容受性的标志物。大麻的广泛使用及其已知的对生殖的不利影响将这项研究归类为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.