Botanical Chemicals and Ovotoxicity

描述(申请人提供)：女性通过饮食接触到几种植物化合物，或因为它们被用作预防或治疗各种疾病的药物，包括癌症、肾脏疾病、神经元损伤、性功能障碍、炎症、抑郁和更年期症状。虽然研究表明，植物化合物可能对治疗一些不利条件有用，但其副作用还不太清楚。不幸的是，很少有研究考察植物化合物对卵巢功能的影响，如大豆制品(金雀异黄素、马兜铃素)、甘草(异奎利汀)和角质山羊杂草(淫羊藿苷)。因此，拟议研究的目标是使用成年小鼠模型来检验这样的假设，即选定的植物化合物(即大豆制品(染料木素、木犀草素)、甘草根(异奎利特)和角质山羊杂草(淫羊藿苷))减少雌二醇(E2)的合成和/或增加E2代谢，导致E2水平下降；以及E2水平下降导致卵泡生长缓慢和闭锁。为了验证这一假设，我们提出了以下两个特定目标：1)确定选定的植物化合物是否通过抑制合成E2所需的酶的表达和/或诱导有腔卵泡中参与E2代谢的酶的表达来导致低E2水平；以及2)确定选定的植物化合物是否导致有腔卵泡生长缓慢和/或闭锁增加。拟议的研究结果将为植物化合物对成年卵巢的影响提供新的和重要的信息。这些信息将有助于确定植物性化学品的风险和好处。2.

DESCRIPTION (provided by applicant): Women are exposed to several botanical compounds through their diet or because they are being used as agents to prevent or treat a variety of conditions, including cancer, kidney disease, neuronal injury, sexual dysfunction, inflammation, depression, and menopausal symptoms. While studies indicate that botanical compounds may be useful in treating some adverse conditions, the side effects are less well understood. Unfortunately, very few studies have examined the effects of botanical compounds such as soy products (genistein, equol), licorice root (isoquiritigenin), and horny goat weed (icariin) on ovarian function. Thus, the goal of the proposed studies is to use an adult mouse model to test the hypothesis that selected botanical compounds (i.e., soy products (genistein, equol), licorice root (isoquiritigenin), and horny goat weed (icariin)) decrease estradiol (E2) synthesis and/or increase E2 metabolism, leading to decreased E2 levels; and that the decreased E2 levels lead to slow follicular growth and atresia. To test this hypothesis, we propose the following two specific aims: 1) determine whether selected botanical compounds cause low E2 levels by inhibiting expression of enzymes required for E2 synthesis and/or inducing expression of the enzymes involved in metabolism of E2 in antral follicles and 2) determine whether selected botanical compounds cause slow growth and/or increased atresia of antral follicles. The results from the proposed studies will provide novel and important information on the effects of botanical compounds on the adult ovary. This information will be useful for determining the risks and benefits of botanical chemicals. 2