Botanical Chemicals and Ovotoxicity

描述（由申请人提供）：女性通过饮食接触到几种植物化合物，或者因为它们被用作预防或治疗各种疾病的药物，包括癌症、肾病、神经损伤、性功能障碍、炎症、抑郁和更年期症状。虽然研究表明植物性化合物可能对治疗某些不良病症有用，但其副作用却鲜为人知。不幸的是，很少有研究检查植物化合物如大豆制品（染料木素、马酚）、甘草根（异奎里黄素）和山羊角草（淫羊藿苷）对卵巢功能的影响。因此，拟议研究的目标是使用成年小鼠模型来验证所选植物化合物（即豆制品（染料木素，马酚），甘草根（异藜素）和角质山羊草（淫羊藿苷））减少雌二醇（E2）合成和/或增加E2代谢，导致E2水平降低的假设；E2水平降低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具体目标：1)确定选定的植物化合物是否通过抑制E2合成所需的酶的表达和/或诱导窦卵泡中E2代谢相关酶的表达而导致E2水平降低；2)确定选定的植物化合物是否导致窦卵泡生长缓慢和/或闭锁加剧。这些研究结果将为植物性化合物对成年卵巢的作用提供新的重要信息。这些信息将有助于确定植物性化学品的风险和益处。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