雄激素1,4-雄烯二酮和雄烯二酮对斑马鱼胚胎昼夜节律和下丘脑-垂体-性腺轴通路中基因转录表达的影响Effect of Androstadienedione and Androstenedione on Transcription of Genes in Circadian Rhythm and Hypothalamic-pituitary-gonadal Axis in Zebrafish Embryos
马栋栋;蒋宇霞;杨雷;应光国;史文俊;
摘要(Abstract):
雄激素1,4-雄烯二酮(androstadienedione, ADD)和雄烯二酮(androstenedione, AED)主要用于人类和牲畜疾病的预防和治疗。近年来,ADD和AED的大量使用导致其在河流中广泛检出,甚至在多种鱼类体内亦有检出,且浓度较高。ADD和AED已被证实对鱼类具有生殖毒性和发育毒性,但ADD和AED在转录水平上对鱼类的影响鲜有报道。为探究ADD和AED分子水平毒性,本研究考察了斑马鱼胚胎暴露于ADD(4.48、30.0和231 ng·L~(-1))和AED(3.64、21.7和230 ng·L~(-1))144 h后,对其昼夜节律和下丘脑-垂体-性腺轴(hypothalamic-pituitary-gonadal axis, HPG axis)通路中基因转录表达的影响。结果表明,所有浓度的ADD都显著上调了昼夜节律通路中生物钟基因(per1b)、核受体亚族1的D群基因(nr1d2b)、隐花色素基因(cry5)和si:ch211-132b12.7的转录水平,30.0和231 ng·L~(-1)的ADD下调了时钟节律调节因子基因(clocka)和芳香烃受体核转录蛋白样基因(arntl2)的转录水平。3.64 ng·L~(-1)AED显著增强了per1b和nr1d2b的转录表达。此外在HPG轴中,30.0 ng·L~(-1)ADD显著降低了促黄体生成素V亚基基因(lhb)的转录表达水平,而3.64 ng·L~(-1)AED显著上调了lhb的转录表达水平。值得注意的是,4.48ng·L~(-1)ADD和3.64 ng·L~(-1)AED均显著降低了细胞色素P450的11亚族基因(cyp11b)的转录表达水平。上述研究表明,ADD和AED对昼夜节律和HPG轴中相关基因的转录表达有显著性影响,对斑马鱼具有潜在的内分泌干扰风险。
关键词(KeyWords): 1,4-雄烯二酮;雄烯二酮;斑马鱼胚胎;内分泌干扰;昼夜节律;下丘脑-垂体-性腺轴
基金项目(Foundation): 国家自然科学基金资助项目(41807480);; 中国博士后科学基金面上项目(2018M643116);; 华南师范大学研究生创新计划资助项目(2018LKXM018)
作者(Author): 马栋栋;蒋宇霞;杨雷;应光国;史文俊;
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