Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review.

Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review.
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内分泌干扰物通过多种机制作用于雌激素和雄激素途径导致生殖障碍:综述。

DOI:
10.3390/ijerph18041464
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发表时间:
2021-02-04
影响因子:
--
通讯作者:
Tsatsakis A
Tsatsakis A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Amir S;Shah STA;Mamoulakis C;Docea AO;Kalantzi OI;Zachariou A;Calina D;Carvalho F;Sofikitis N;Makrigiannakis A;Tsatsakis A

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诸如内分泌干扰化学品(EDCs)等有毒化合物对环境的污染日益严重,是造成两性生殖缺陷的主要原因之一。雌激素/雄激素途径在性腺发育、第二性征的决定和配子发生中至关重要。大多数EDC通过各自的受体和/或下游信号传导介导其作用。本文的目的是强调内分泌干扰物可以触发拮抗或激动反应的机制,通过雌激素/雄激素受体发挥作用,导致生殖缺陷,从而导致不孕。在体外,在体内和在硅片上的研究集中在雌激素/雄激素途径和相关蛋白质的影响,在过去的十年中发表的审查被认为是。使用PUBMED和PUBCHEM进行文献检索。EDCs可与雌激素受体(ERα和ERβ)和雄激素受体结合或激活替代受体如G蛋白偶联受体(GPCR)、GPR 30、雌激素相关受体(ERRγ),从而通过下游激酶激活雌激素信号传导。双酚A、二氯二苯三氯乙烷、二氯二苯二氯乙烯、多氯联苯和邻苯二甲酸酯是通过多种方式干扰正常雌激素/雄激素途径导致两性不育的主要毒物,包括精子中的DNA损伤、甲基化模式改变、组蛋白修饰和miRNA表达。
Increasing contamination of the environment by toxic compounds such as endocrine disrupting chemicals (EDCs) is one of the major causes of reproductive defects in both sexes. Estrogen/androgen pathways are of utmost importance in gonadal development, determination of secondary sex characteristics and gametogenesis. Most of the EDCs mediate their action through respective receptors and/or downstream signaling. The purpose of this review is to highlight the mechanism by which EDCs can trigger antagonistic or agonistic response, acting through estrogen/androgen receptors causing reproductive defects that lead to infertility. In vitro, in vivo and in silico studies focusing on the impact of EDCs on estrogen/androgen pathways and related proteins published in the last decade were considered for the review. PUBMED and PUBCHEM were used for literature search. EDCs can bind to estrogen receptors (ERα and ERβ) and androgen receptors or activate alternative receptors such as G protein-coupled receptors (GPCR), GPR30, estrogen-related receptor (ERRγ) to activate estrogen signaling via downstream kinases. Bisphenol A, dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethylene, polychlorinated biphenyls and phthalates are major toxicants that interfere with the normal estrogen/androgen pathways leading to infertility in both sexes through many ways, including DNA damage in spermatozoids, altered methylation pattern, histone modifications and miRNA expression.
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