Endocrine disruptors, gene deregulation and male germ cell tumors
Endocrine disruptors, gene deregulation and male germ cell tumors
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DOI：
10.1387/ijdb.130042jd
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发表时间：
2013-01-01
影响因子：
0.7
通讯作者：
De Felici, Massimo
中科院分区：
文献类型：
--
作者：
Del Mazo, Jesus;Brieno-Enriquez, Miguel A.;De Felici, Massimo
内分泌干扰物（EDs）是一类环境污染物，通过改变生物体内激素平衡和细胞发育分化过程中基因调控的正常模式，改变生物体内环境的稳定性。因此，雄性性腺的发育及其功能可能会受到特定ED或其混合物的影响。这些生殖毒性剂导致生殖系统病变（如睾丸癌）的分子作用机制很复杂，尚未得到很好的表征。然而，这些化合物可能会改变风险窗口中基因调控机制和功能基因网络之间的相互作用，主要是在胚胎发育期间。此外，这种变化可以通过表观遗传机制代代相传。存在ED对发育中睾丸中mRNA、小的非编码RNA和表观遗传标记的表达的作用的实例，所述发育中睾丸与生殖细胞肿瘤中发现的细胞和分子改变相关。在本综述中，我们将讨论与睾丸发育，暴露于ED和生殖细胞肿瘤的发生有关的遗传，转录组和表观遗传变化的各个方面。
Endocrine disruptors (EDs) belong to a large group of compounds, usually present as environmental pollutants, which can alter the homeostasis of living organisms by modifying hormonal balance and changing the normal patterns of gene regulation during development and cell differentiation. Hence, the development of male gonads and their functionality may be affected by exposure to specific EDs or their mixtures. The molecular mechanisms of action of these reprotoxicants leading to pathologies of the reproductive system such as testicular cancer, are complex and not well characterized. It is likely, however, that these compounds alter the interaction between the mechanisms of gene regulation and functional gene networks in windows of risk, mainly during embryonic development. Moreover, such changes could be transmitted through generations by epigenetic mechanisms. There are examples of the action of EDs on the expression of mRNAs, small non-coding RNAs and epigenetic marks in the developing testis associated with cellular and molecular alterations found in germ cell tumors. In the present review, we will discuss various aspects of genetic, transcriptomic and epigenetic changes related to testicular development, exposure to EDs and the occurrence of germ cell tumors.