Sexually dimorphic transcriptomic responses in the teleostean hypothalamus: a case study with the organochlorine pesticide dieldrin.

Sexually dimorphic transcriptomic responses in the teleostean hypothalamus: a case study with the organochlorine pesticide dieldrin.
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在静脉下下丘脑中的性二态转录组反应:用有机氯农药dieldrin的案例研究。

DOI:
10.1016/j.neuro.2012.09.012
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发表时间:
2013-01
期刊:
影响因子:
3.4
通讯作者:
Denslow, Nancy D.
Denslow, Nancy D.
中科院分区:
医学3区
文献类型:
--
作者:
Martyniuk, Christopher J.;Doperalski, Nicholas J.;Kroll, Kevin J.;Barber, David S.;Denslow, Nancy D.

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有机氯农药(OCPs)如狄氏剂是一类持久性水生污染物,对脊椎动物的神经和生殖造成不利影响。在本研究中,雌性和雄性大口黑鲈(Micropterus salmoides) (LMB)在2个月的饲养暴露中(8 - 10月)暴露于3mg狄氏剂/kg饲料中,以(1)确定下丘脑对狄氏剂的转录反应是否在两性之间保守;(2)表征狄氏剂神经毒性的细胞信号级联;(3)确定与17β-雌二醇(E2)(一种具有神经保护作用的激素)共同喂养是否会减轻雄性对狄氏剂的反应。尽管雌激素也很弱,但狄氏剂治疗并没有引起生殖终点的变化(如促性腺指数、卵黄蛋白原或血浆E2)。子网络(SNEA)和基因集富集分析(GSEA)显示,狄氏剂暴露后神经激素网络、神经递质和核受体信号以及激活素信号网络发生改变。最引人注目的是,通过基因集富集鉴定的大多数细胞通路在雌性中显著增加,而在喂食狄氏剂的雄性中,大多数细胞通路显著减少。这些数据表明:(1)硬骨鱼下丘脑存在两性二态反应;(2)在转录组学水平上,神经递质系统是狄氏剂的靶标;(3)共同喂食狄氏剂和E2的雄性下丘脑基因和细胞通路的改变数量最少,表明E2可能减轻狄氏剂对中枢神经系统的影响。
Organochlorine pesticides (OCPs) such as dieldrin are a persistent class of aquatic pollutants that cause adverse neurological and reproductive effects in vertebrates. In this study, female and male largemouth bass (Micropterus salmoides) (LMB) were exposed to 3 mg dieldrin/kg feed in a 2 month feeding exposure (August–October) to (1) determine if the hypothalamic transcript responses to dieldrin were conserved between the sexes; (2) characterize cell signaling cascades underlying dieldrin neurotoxicity; and (3) determine whether or not co-feeding with 17β-estradiol (E2), a hormone with neuroprotective roles, mitigates responses in males to dieldrin. Despite also being a weak estrogen, dieldrin treatments did not elicit changes in reproductive endpoints (e.g. gonadosomatic index, vitellogenin, or plasma E2). Sub-network (SNEA) and gene set enrichment analysis (GSEA) revealed that neuro-hormone networks, neurotransmitter and nuclear receptor signaling, and the activin signaling network were altered by dieldrin exposure. Most striking was that the majority of cell pathways identified by the gene set enrichment were significantly increased in females while the majority of cell pathways were significantly decreased in males fed dieldrin. These data suggest that (1) there are sexually dimorphic responses in the teleost hypothalamus; (2) neurotransmitter systems are a target of dieldrin at the transcriptomics level; and (3) males co-fed dieldrin and E2 had the fewest numbers of genes and cell pathways altered in the hypothalamus, suggesting that E2 may mitigate the effects of dieldrin in the central nervous system.
DOI: 10.1186/1756-6606-1-12
发表时间: 2008-10-22
期刊: Molecular brain
影响因子: 3.6
作者:
Kanthasamy AG;Kitazawa M;Yang Y;Anantharam V;Kanthasamy A
通讯作者: Kanthasamy A
DOI: 10.1016/j.neuro.2004.07.010
发表时间: 2005-08-01
期刊: NEUROTOXICOLOGY
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作者:
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发表时间: 2010-02-01
影响因子: 9.8
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通讯作者: Bolgrien, David W.
DOI: 10.1016/0041-008x(87)90206-7
发表时间: 1987-05-01
影响因子: 3.8
作者:
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通讯作者: ELDEFRAWI, AT
DOI: 10.1007/s00244-003-0275-2
发表时间: 2005-05-01
影响因子: 4
作者:
Gelsleichter, J;Manire, CA;Lombardi-Carlson, L
通讯作者: Lombardi-Carlson, L