The Role of Endocrine Disruptors in the Epigenetics of Reproductive Disease and Dysfunction: Potential Relevance to Humans.
The Role of Endocrine Disruptors in the Epigenetics of Reproductive Disease and Dysfunction: Potential Relevance to Humans.
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DOI：
10.1007/s13669-012-0014-7
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发表时间：
2012-09-01
影响因子：
0.5
通讯作者：
Osteen, Kevin G
中科院分区：
文献类型：
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作者：
Bruner-Tran, Kaylon L;Resuehr, David;Ding, Tianbing;Lucas, John A;Osteen, Kevin G
在小鼠模型中，我们将生命早期接触有毒物质与子宫对孕酮的敏感性降低联系起来，我们之前认为这种表型与子宫内膜异位症患者的炎症有关。随后的研究表明，发育毒物暴露不仅会降低雄性和雌性小鼠的生育能力，还会对妊娠产生负面影响，导致自发性早产（PTB）。黄体酮受体基因的表观遗传改变与生育能力下降和不良妊娠结局相关，并且在没有额外接触有毒物质的情况下，这种改变在多代小鼠中持续存在。女性基因与环境的相互作用可以解释为什么一些“有 PTB 风险”的患者足月分娩，而另一些没有已知风险的患者则提前分娩。我们的模型提供了一个独特的系统来揭示炎症和孕酮反应性降低对 PTB 的相互作用影响，并表明治疗需要在怀孕前开始（并涉及双方），而不是在炎症级联反应启动后开始。
In a murine model, we have linked early life toxicant exposure to reduced uterine sensitivity to progesterone, a phenotype we had previously associated with inflammation in endometriosis patients. Subsequent studies revealed that developmental toxicant exposure not only reduces fertility in male and female mice but also negatively impacts pregnancy leading to spontaneous preterm birth (PTB). An epigenetic alteration of the progesterone receptor gene correlated with reduced fertility and adverse pregnancy outcomes and persisted in multiple generations of mice in the absence of an additional toxicant exposure. Gene-environment interactions in women may explain why some patients “at risk” for PTB deliver at term while others without known risks deliver early. Our model provides a unique system to unravel the interactive influences of inflammation and reduced progesterone responsiveness on PTB and suggests that therapy needs to begin prior to pregnancy (and involve both partners) rather than once the inflammatory cascade has been initiated.