Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Biochem Pharmacol. 2022 Jan;195:114848. doi: 10.1016/j.bcp.2021.114848. Epub 2021 Nov 18.
Exposure to naturally derived estrogen receptor activators, such as the phytoestrogen genistein, can occur at physiologically relevant concentrations in the human diet. Soy-based infant formulas are of particular concern because infants consuming these products have serum genistein levels almost 20 times greater than those seen in vegetarian adults. Comparable exposures in animal studies have adverse physiologic effects. The timing of exposure is particularly concerning because infants undergo a steroid hormone-sensitive period termed "minipuberty" during which estrogenic chemical exposure may alter normal reproductive tissue patterning and function. The delay between genistein exposure and reproductive outcomes poses a unique challenge to collecting epidemiological data. In 2010, the U.S. National Toxicology Program monograph on the safety of the use of soy formula stated that the use of soy-based infant formula posed minimal concern and emphasized a lack of data from human subjects. Since then, several new human and animal studies have advanced our epidemiological and mechanistic understanding of the risks and benefits of phytoestrogen exposure. Here we aim to identify clinically relevant findings regarding phytoestrogen exposure and female reproductive outcomes from the past 10 years, with a focus on the phytoestrogen genistein, and explore the implications of these findings for soy infant formula recommendations. Research presented in this review will inform clinical practice and dietary recommendations for infants based on evidence from both clinical epidemiology and basic research advances in endocrinology and developmental biology from mechanistic in vitro and animal studies.
暴露于天然雌激素受体激活剂，如植物雌激素染料木黄酮，可能会以生理相关浓度出现在人类饮食中。基于大豆的婴儿配方奶粉特别令人担忧，因为食用这些产品的婴儿的血清染料木黄酮水平几乎是素食成年人的 20 倍。类似的动物研究暴露会产生不良的生理影响。暴露的时间特别令人担忧，因为婴儿在“小青春期”期间经历一个类固醇激素敏感时期，在此期间，雌激素化学物质暴露可能会改变正常的生殖组织模式和功能。染料木黄酮暴露和生殖结果之间的时间延迟给收集流行病学数据带来了独特的挑战。2010 年，美国国家毒理学计划关于使用大豆配方的安全性的专论指出，使用基于大豆的婴儿配方奶粉的风险极小，并强调缺乏来自人体研究的数据。自那时以来，几项新的人类和动物研究提高了我们对植物雌激素暴露的风险和益处的流行病学和机制理解。在这里，我们旨在确定过去 10 年中与植物雌激素暴露和女性生殖结果相关的临床相关发现，重点是植物雌激素染料木黄酮，并探讨这些发现对大豆婴儿配方奶粉建议的影响。本综述中提出的研究将根据临床流行病学以及内分泌学和发育生物学的基础研究进展，为基于体外和动物研究的机制的婴儿提供临床实践和饮食建议。
