Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models.
Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models.
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DOI：
10.1016/j.reprotox.2016.07.007
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Osteen KG
中科院分区：
文献类型：
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作者：
Bruner-Tran KL;Gnecco J;Ding T;Glore DR;Pensabene V;Osteen KG
人类和其他动物暴露在各种各样的人造毒物中，其中许多作为内分泌干扰物，在整个生命周期内表现出不同的影响。在人类中，虽然成人接触某些化合物的影响是已知的，但发育过程中接触内分泌干扰物(EDCs)的潜在后果更难确定。动物研究表明，青春期前暴露于EDCs可导致成人生殖疾病和功能障碍。具体地说，在早期接触2，3，7，8-四氯二苯并-对二恶英(TCDD)的成年雌性小鼠中，我们证明了几种与女性子宫内膜异位症有关的生殖疾病的跨代发生。在这里，我们回顾了与TCDD相关的成人生殖疾病发生的证据，以及与TCDD和/或子宫内膜异位症相关的已知表观遗传学改变。我们还将引入新的“芯片上的器官”模型，与我们已建立的小鼠模型相结合，有望进一步增强我们检查导致遗传病的基因-环境相互作用变化的能力。
Humans and other animals are exposed to a wide array of man-made toxicants, many of which act as endocrine disruptors that exhibit differential effects across the lifespan. In humans, while the impact of adult exposure is known for some compounds, the potential consequences of developmental exposure to endocrine disrupting chemicals (EDCs) is more difficult to ascertain. Animal studies have revealed that exposure to EDCs prior to puberty can lead to adult reproductive disease and dysfunction. Specifically, in adult female mice with an early life exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), we demonstrated a transgenerational occurrence of several reproductive diseases that have been linked to endometriosis in women. Herein, we review the evidence for TCDD-associated development of adult reproductive disease as well as known epigenetic alterations associated with TCDD and/or endometriosis. We will also introduce new “Organ-on-Chip” models which, combined with our established murine model, are expected to further enhance our ability to examine alterations in gene-environment interactions that lead to heritable disease.