Reproductive and Developmental Impact of Dietary Phytoestrogens

植物雌激素(PE)是一类植物来源的化合物，在结构和功能上都与哺乳动物雌激素相似。一些饮食中的异黄酮，如染料木素和大豆苷元，由于其雌激素受体依赖活性水平较高，且在大豆食品中的浓度较高，因此与其他异黄酮类相比相当突出。因此，这些化合物可能通过扰乱体内微妙的内分泌平衡而发挥内分泌干扰物(EDs)的作用，并对生殖系统和其他雌激素敏感组织产生不利影响。在发育的关键时期暴露于雌激素物质可能会对区分雌激素敏感的器官产生不利后果。此外，如果胎儿和新生儿的母亲摄入了过量的大豆，或者给他们吃了大豆配方奶粉和其他专门为儿童销售的大豆产品，那么他们可能会接触到高水平的异黄酮类。因此，应重视膳食体育对婴幼儿和青少年健康的不利影响，一方面是每公斤体重异黄酮暴露量较高的人群，另一方面是性激素水平相对较低和外源性雌激素敏感性较高的个体。到目前为止，膳食PE如染料木素和大豆苷元在人类雌激素敏感器官发育中的作用尚未有定论。在一个协调一致的研究概念内，我们计划调查在发育的关键时期饮食PE暴露的影响。因此，将在模拟不同暴露情景的动物模型中研究PE对雄性和雌性生殖和激素敏感组织的发育、代谢和表观遗传调节的影响，并确定合适的生物标志物。此外，还将在适应的细胞模型中研究发育过程中PE活性的分子机制。为了从机制上传递对人体状况的研究结果，将对食用大豆食品的儿童(中国和德国)的血清和血细胞进行分析，目的是寻找饮食体育风险评估的通用生物标志物，并阐明欧洲和中国人群对饮食体育反应的差异。

Phytoestrogens (PE) are a diverse group of plant-derived compounds that mimic mammalian estrogens both structurally and functionally. Some dietary isoflavones such as genistein and daidzein are quite outstanding comparing with others due to their higher level of estrogen receptor-dependent activity and higher concentration in soy food. Therefore these compounds may act as endocrine disruptors (EDs) by perturbing the delicate endocrine balance in vivo and possess adverse effects especially on the reproductive system and other estrogen-sensitive tissues. Exposure to estrogenic substances during critical periods of development can have adverse consequences on differentiating estrogen-sensitive organs. Moreover, human fetuses and neonates can be exposed to high levels of isoflavones if their mothers consume excessive amounts of soy or if they are given soy-based formulas and other soy products marketed specifically for children. Therefore, due attention should be paid on the adverse impacts of dietary PE on health of infants, children and adolescents which are on one hand the group with the higher isoflavone exposure level per Kg body weight on the other hand the individuals with a relative lower sexual-hormone level and a higher exogenous estrogenic substance sensitivity. Up to date, the involvement of dietary PE such as genistein and daidzein in human estrogen-sensitive organs’ development has not been conclusive. Within a coordinated research concept we plan to investigate the influence of dietary PE exposure during critical periods of development. Therefore the impact of PE on the development of the male and female reproductive and hormone sensitive tissues, metabolism and epigenetic modulations will be studied in animal models simulating different exposure scenarios and suitable biomarkers will be identified. In addition molecular mechanisms of PE activity during development will be studied in adapted cell models. To transfer the mechanistically findings on the human situation, serum and blood cells from children consuming soy food (both in China and Germany) will be analyzed with the aim to discover universal biomarkers for dietary PE risk assessment and elucidate the differences of reactions to dietary PE in European and Chinese population groups.