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Endocrine disruption of oestrogen action and female reproductive tract cancers

机译:内分泌破坏雌激素作用和女性生殖道癌症

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摘要

Endocrine disrupting chemicals (EDC) are ubiquitous and persistent compounds that have the capacity to interfere with normal endocrine homoeostasis. The female reproductive tract is exquisitely sensitive to the action of sex steroids, and oestrogens play a key role in normal reproductive function. Malignancies of the female reproductive tract are the fourth most common cancer in women, with endometrial cancer accounting for most cases. Established risk factors for development of endometrial cancer include high BMI and exposure to oestrogens or synthetic compounds such as tamoxifen. Studies on cell and animal models have provided evidence that many EDC can bind oestrogen receptors and highlighted early life exposure as a window of risk for adverse lifelong effects on the reproductive system. The most robust evidence for a link between early life exposure to EDC and adverse reproductive health has come from studies on women who were exposed in utero to diethylstilbestrol. Demonstration that EDC can alter expression of members of the HOX gene cluster highlights one pathway that might be vulnerable to their actions. In summary, evidence for a direct link between EDC exposure and cancers of the reproductive system is currently incomplete. It will be challenging to attribute causality to any single EDC when exposure and development of malignancy may be separated by many years and influenced by lifestyle factors such as diet (a source of phytoestrogens) and adiposity. This review considers some of the evidence collected to date.
机译:内分泌干​​扰化学物质(EDC)是普遍存在的持久性化合物,具有干扰正常内分泌同源性的能力。女性生殖道对性类固醇的作用极为敏感,而雌激素在正常生殖功能中起关键作用。女性生殖道恶性肿瘤是女性中第四大常见癌症,子宫内膜癌占大多数。子宫内膜癌发展的既定危险因素包括高BMI和暴露于雌激素或他莫昔芬等合成化合物。对细胞和动物模型的研究提供了证据,表明许多EDC可以结合雌激素受体,并强调了早期生命暴露是对生殖系统造成终身不利影响的风险之窗。关于生命早期暴露于EDC与不利生殖健康之间联系的最有力证据来自对子宫内暴露于己烯雌酚的妇女的研究。 EDC可以改变HOX基因簇成员表达的证明突出了一条可能容易受到其作用的途径。总之,目前尚不完全证明EDC暴露与生殖系统癌症之间存在直接联系。当恶性肿瘤的暴露和发展可能会分开很多年并受到生活方式因素(例如饮食(植物雌激素的来源)和肥胖症)的影响时,将因果关系归因于任何单个EDC都是具有挑战性的。该评价考虑了迄今为止收集的一些证据。

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