Disruption of global hypothalamic microRNA (miR) profiles and associated behavioral changes in California mice (Peromyscus californicus) developmentally exposed to endocrine disrupting chemicals.
Disruption of global hypothalamic microRNA (miR) profiles and associated behavioral changes in California mice (Peromyscus californicus) developmentally exposed to endocrine disrupting chemicals.
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DOI：
10.1016/j.yhbeh.2020.104890
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发表时间：
2021-03
影响因子：
3.5
通讯作者：
Rosenfeld CS
中科院分区：
文献类型：
--
作者：
Kaur S;Kinkade JA;Green MT;Martin RE;Willemse TE;Bivens NJ;Schenk AK;Helferich WG;Trainor BC;Fass J;Settles M;Mao J;Rosenfeld CS
发育过程中接触内分泌干扰化学物质 (EDC)，例如双酚 A (BPA) 或金雀异黄素 (GEN)，会导致长期的表观基因组效应。 MicroRNA (miR) 调节哪些 mRNA 将被翻译为蛋白质，从而充当表观遗传控制的最终检查点。然而，EDC 是否影响神经 miRNA (miR) 模式尚不清楚。我们的目的是测试以下假设：加州小鼠 (Peromyscus californicus) 在发育过程中接触 GEN、BPA 或这两种化学物质会影响下丘脑 miR/小 RNA 谱，并确定此类生物分子改变与行为和代谢变化的相关程度。加州小鼠在发育过程中暴露于 GEN（250 mg/kg 饲料重量，FW）、GEN（250 mg/kg FW）+ BPA（5 mg/kg FW）、低剂量（LD）BPA（5 mg/kg FW）或高剂量 BPA（50 mg/kg FW）。成年后代接受了一系列行为和代谢测试；随后，对小鼠实施安乐死，收集冷冻大脑，从下丘脑穿孔中分离出小RNA，并随后进行小RNA测序。暴露于一种或两种 EDC 的加州小鼠会出现一种或多种重复行为。 GEN、LD BPA 和 UD BPA 改变了超声波和可听发声的方面。每次 EDC 暴露都会导致差异表达 miR/小 RNA 的性别依赖性差异，其中 miR7-2、miR146 和 miR148a 在所有女性和男性 EDC 暴露组中均增加。目前的研究结果表明，发育时期接触 GEN 和/或 BPA 会影响下丘脑 miR/小 RNA 表达模式，并且这种变化与 EDC 诱导的行为和代谢改变相关。 miR146 可能是哺乳动物（包括人类）EDC 暴露的重要介质和生物标志物。
Developmental exposure to endocrine disrupting chemicals (EDCs), e.g., bisphenol A (BPA) or genistein (GEN), causes longstanding epigenome effects. MicroRNAs (miRs) regulate which mRNAs will be translated to proteins and thereby serve as the final checkpoint in epigenetic control. Scant amount is known, however, whether EDCs affect neural miRNA (miR) patterns. We aimed to test the hypothesis that developmental exposure of California mice (Peromyscus californicus) to GEN, BPA, or both chemicals influences hypothalamic miR/small RNA profiles and ascertain the extent such biomolecular alterations correlate with behavioral and metabolic changes. California mice were developmentally exposed to GEN (250 mg/kg feed weight, FW), GEN (250 mg/kg FW) + BPA (5 mg/kg FW), low dose (LD) BPA (5 mg/kg FW), or upper dose BPA (50 mg/kg FW). Adult offspring were tested in a battery of behavioral and metabolic tests; whereupon, mice were euthanized, frozen brains collected, small RNAs were isolated from hypothalamic punches, and subsequent small RNA sequencing. California mice exposed to one or both EDCs engaged in one or more repetitive behaviors. GEN, LD BPA, and UD BPA altered aspects of ultrasonic and audible vocalizations. Each EDC exposure led to sex-dependent differences in differentially expressed miR/small RNAs with miR7-2, miR146, and miR148a being increased in all female and male EDC exposed groups. Current findings reveal that developmental exposure to GEN and/or BPA affects hypothalamic miR/small RNA expression patterns, and such changes correlate with EDC-induced behavioral and metabolic alterations. miR146 is likely an important mediator and biomarker of EDC exposure in mammals, including humans.
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影响因子：
3.5
作者：
Harris EP;Allardice HA;Schenk AK;Rissman EF
通讯作者：
Rissman EF
DOI：
10.1017/s2040174415001488
发表时间：
2015-12
影响因子：
1.7
作者：
Johnson SA;Painter MS;Javurek AB;Ellersieck MR;Wiedmeyer CE;Thyfault JP;Rosenfeld CS
通讯作者：
Rosenfeld CS
影响因子：
--
作者：
Alonso, Ana;Gonzalez-Pardo, Hector;Gonzalez, Celestino
通讯作者：
Gonzalez, Celestino
影响因子：
2.7
作者：
De Felice B;Manfellotto F;Palumbo A;Troisi J;Zullo F;Di Carlo C;Di Spiezio Sardo A;De Stefano N;Ferbo U;Guida M;Guida M
通讯作者：
Guida M
影响因子：
3.2
作者：
Chou, Wei-Chun;Lee, Pei-Hsuan;Chuang, Chun-Yu
通讯作者：
Chuang, Chun-Yu