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首页> 外文期刊>Environmental Epigenetics >Endocrine-disrupting chemicals, epigenetics, and skeletal system dysfunction: exploration of links using bisphenol A as a model system
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Endocrine-disrupting chemicals, epigenetics, and skeletal system dysfunction: exploration of links using bisphenol A as a model system

机译：破坏内分泌的化学物质，表观遗传学和骨骼系统功能障碍：使用双酚A作为模型系统探索连接

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Early life exposures to endocrine-disrupting chemicals (EDCs) have been associated with physiological changes of endocrine-sensitive tissues throughout postnatal life. Although hormones play a critical role in skeletal growth and maintenance, the effects of prenatal EDC exposure on adult bone health are not well understood. Moreover, studies assessing skeletal changes across multiple generations are limited. In this article, we present previously unpublished data demonstrating dose-, sex-, and generation-specific changes in bone morphology and function in adult mice developmentally exposed to the model estrogenic EDC bisphenol A (BPA) at doses of 10?μg (lower dose) or 10?mg per kg bw/d (upper dose) throughout gestation and lactation. We show that F1 generation adult males, but not females, developmentally exposed to bisphenol A exhibit dose-dependent reductions in outer bone size resulting in compromised bone stiffness and strength. These structural alterations and weaker bone phenotypes in the F1 generation did not persist in the F2 generation. Instead, F2 generation males exhibited greater bone strength. The underlying mechanisms driving the EDC-induced physiological changes remain to be determined. We discuss potential molecular changes that could contribute to the EDC-induced skeletal effects, with an emphasis on epigenetic dysregulation. Furthermore, we assess the necessity of intact sex steroid receptors to mediate these effects. Expanding future assessments of EDC-induced effects to the skeleton may provide much needed insight into one of the many health effects of these chemicals and aid in regulatory decision making regarding exposure of vulnerable populations to these chemicals.
机译：生命早期接触内分泌干扰化学物质（EDC）与整个出生后内分泌敏感组织的生理变化有关。尽管激素在骨骼生长和维持中起着至关重要的作用，但人们对产前EDC暴露对成年骨骼健康的影响还知之甚少。而且，评估多代骨骼变化的研究是有限的。在本文中，我们介绍了以前未公开的数据，这些数据证明了以10？μg（低剂量）的剂量暴露于模型雌激素EDC双酚A（BPA）的成年小鼠的骨骼形态和功能的剂量，性别和世代特异性变化。 ）或在整个妊娠和哺乳期每公斤体重10毫克（每天）。我们显示F1代成年男性，而不是女性，发育暴露于双酚A时，外骨骼尺寸显示出剂量依赖性降低，从而导致骨刚度和强度受损。 F1代中的这些结构改变和较弱的骨表型在F2代中不存在。相反，F2代雄性表现出更大的骨骼强度。驱动EDC引起的生理变化的潜在机制尚待确定。我们讨论了可能导致EDC诱导的骨骼效应的潜在分子变化，重点是表观遗传失调。此外，我们评估了完整的性类固醇受体介导这些作用的必要性。扩大对EDC引起的骨骼影响的未来评估，可能会为这些化学物质对健康的多种影响之一提供急需的洞察力，并有助于就弱势人群接触这些化学物质做出监管决策。

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