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Reproductive and Developmental Impact of Dietary Phytoestrogens

膳食植物雌激素对生殖和发育的影响

基本信息

批准号：
224980381
负责人：
Professor Dr. Patrick Diel
金额：
--
依托单位：
Abteilung II: Molekulare und Zelluläre Sportmedizin
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2012
资助国家：
德国
起止时间：
2011-12-31 至 2015-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/224980381?language=en
关键词：
Reproductive Developmental Impact Dietary Phytoestrogens

项目摘要

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.

植物雌激素（PE）是一类在结构和功能上都能模拟哺乳动物雌激素的植物源化合物。一些膳食雌激素，如染料木素和大豆黄酮是相当突出的，与其他相比，由于其较高的雌激素受体依赖活性和较高的浓度在大豆食品。因此，这些化合物可作为内分泌干扰物（ED），扰乱体内微妙的内分泌平衡，并具有不良影响，特别是对生殖系统和其他雌激素敏感组织。在发育的关键时期暴露于雌激素物质可能对区分雌激素敏感器官产生不利影响。此外，如果母亲食用过量的大豆，或者给他们提供大豆配方奶粉和其他专门为儿童销售的豆制品，人类胎儿和新生儿可能会接触到高水平的大豆酮。因此，应充分重视膳食PE对婴儿、儿童和青少年健康的不利影响，这类人群一方面是每公斤体重中暴露水平较高的人群，另一方面是性激素水平相对较低和外源性雌激素物质敏感性较高的人群。迄今为止，膳食PE如染料木黄酮和大豆黄酮参与人类雌激素敏感器官的发育尚未有定论。在一个协调的研究概念，我们计划调查的影响，饮食中的PE暴露在发展的关键时期。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，并将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。为了转移人类情况的机制研究结果，将分析食用大豆食品的儿童（中国和德国）的血清和血细胞，旨在发现用于膳食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。