Reproductive and Developmental Impact of Dietary Phytoestrogens

植物雌激素（PE）是一类从植物中衍生的化合物，在结构和功能上都与哺乳动物雌激素相似。一些膳食异黄酮，如染料木黄酮和大豆黄酮，由于其雌激素受体依赖活性较高，在大豆食品中的浓度较高，因此与其他异黄酮相比具有相当突出的作用。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会对雌激素敏感器官的分化产生不利影响。此外，如果胎儿和新生儿的母亲摄入过量的大豆，或者给他们喂食大豆配方奶粉和其他专门为儿童销售的大豆产品，胎儿和新生儿可能会接触到高浓度的异黄酮。因此，应重视膳食PE对婴儿、儿童和青少年健康的不良影响，一方面是每公斤体重异黄酮暴露水平较高的群体，另一方面是性激素水平相对较低和外源性雌激素物质敏感性较高的个体。迄今为止，膳食PE如染料木素和大豆黄酮是否参与人类雌激素敏感器官的发育尚无定论。在一个协调的研究概念中，我们计划调查饮食中PE暴露在发育关键时期的影响。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，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。为了将机理研究结果转移到人类情况，我们将对食用大豆食品的儿童（包括中国和德国）的血清和血细胞进行分析，目的是发现膳食PE风险评估的通用生物标志物，并阐明欧洲和中国人群对膳食PE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.