Janesick Amanda S, Blumberg Bruce
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California; Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, California.
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California; Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, California.
Am J Obstet Gynecol. 2016 May;214(5):559-65. doi: 10.1016/j.ajog.2016.01.182. Epub 2016 Jan 29.
Endocrine disrupting chemicals (EDCs) are defined as exogenous chemicals, or mixtures of chemicals, that can interfere with any aspect of hormone action. The field of endocrine disruption is historically rooted in wildlife biology and reproductive endocrinology where EDCs are demonstrated contributors to infertility, premature puberty, endometriosis, and other disorders. Recently, EDCs have been implicated in metabolic syndrome and obesity. Adipose tissue is a true endocrine organ and, therefore, an organ that is highly susceptible to disturbance by EDCs. A subset of EDCs, called "obesogens," promote adiposity by altering programming of fat cell development, increasing energy storage in fat tissue, and interfering with neuroendocrine control of appetite and satiety. Obesity adds more than $200 billion to US healthcare costs and the number of obese individuals continues to increase. Hence, there is an urgent, unmet need to understand the mechanisms underlying how exposures to certain EDCs may predispose our population to be obese. In this review, we discuss the history of obesogen discovery from its origins in reproductive biology to its latest role in the transgenerational inheritance of obesity in mice. We discuss the development of adipose tissue in an embryo, maintenance of adipocyte number in adults, how EDC disruption programs stem cells to preferentially make more adipocytes, the mechanisms by which chemicals can permanently alter the germline epigenome, and whether there are barriers to EDCs in the gametes.
内分泌干扰化学物质(EDCs)被定义为能够干扰激素作用任何方面的外源性化学物质或化学物质混合物。内分泌干扰领域在历史上扎根于野生动物生物学和生殖内分泌学,在这些领域中,EDCs被证明是导致不孕、性早熟、子宫内膜异位症和其他疾病的因素。最近,EDCs被认为与代谢综合征和肥胖有关。脂肪组织是一个真正的内分泌器官,因此是一个极易受到EDCs干扰的器官。一类被称为“致肥胖物”的EDCs通过改变脂肪细胞发育程序、增加脂肪组织中的能量储存以及干扰食欲和饱腹感的神经内分泌控制来促进肥胖。肥胖给美国医疗保健成本增加了超过2000亿美元,而且肥胖个体的数量持续增加。因此,迫切需要了解某些EDCs暴露如何使我们的人群易患肥胖症的潜在机制,但这一需求尚未得到满足。在这篇综述中,我们讨论了致肥胖物从其在生殖生物学中的起源到其在小鼠肥胖跨代遗传中的最新作用的发现历程。我们讨论了胚胎中脂肪组织的发育、成体中脂肪细胞数量的维持、EDCs如何干扰干细胞程序使其优先产生更多脂肪细胞、化学物质能够永久改变生殖系表观基因组的机制,以及配子中是否存在针对EDCs的屏障。