双酚A对成年雄性小鼠的生殖毒性及其作用机制

doi:10.13481/j.1671-587x.20160201

吉林大学学报(医学版) ›› 2016, Vol. 42 ›› Issue (02): 195-199.doi: 10.13481/j.1671-587x.20160201

• 基础研究 • 下一篇

双酚A对成年雄性小鼠的生殖毒性及其作用机制

郝兴霞¹, 张东泽¹, 于泊洋², 张岩³, 周圆圆⁴, 邱雪迎⁵, 周好乐³, 刘陶迪²

1. 内蒙古医科大学形态学实验中心, 内蒙古呼和浩特 010110;
2. 内蒙古医科大学心身医学实验室, 内蒙古呼和浩特 010110;
3. 内蒙古医科大学遗传学教研室, 内蒙古呼和浩特 010110;
4. 内蒙古医科大学2012级法医专业;
5. 内蒙古医科大学2012级临床医学专业

收稿日期:2015-06-08 出版日期:2016-03-28 发布日期:2016-03-31
通讯作者: 周好乐,教授,硕士研究生导师(Tel:0471-6653181,E-mail:zhl8416@126.com);刘陶迪,教授,硕士研究生导师(Tel:0471-6657543,E-mail:1092027848@qq.com) E-mail:zhl8416@126.com;1092027848@qq.com
作者简介:郝兴霞(1981-),女,内蒙古自治区呼和浩特市人,医学硕士,主要从事生殖系统疾病发生机制方面的研究。
基金资助:
国家自然科学基金资助课题(81260111);内蒙古自治区教育厅高等学校研究项目资助课题(NJZC13439);内蒙古医科大学"英才培育"项目资助课题(2014YCPY002)

Reproductive toxicity of bisphenol A in adult male mice and mechanism

HAO Xingxia¹, ZHANG Dongze¹, YU Boyang², ZHANG Yan³, ZHOU Yuanyuan⁴, QIU Xueying⁵, ZHOU Haole³, LIU Taodi²

1. Experimental Centre of Morphological Practice, Inner Mongolia Medical University, Hohhot 010110, China;
2. Psychosomatic Medicine Laboratory, Inner Mongolia Medical University, Hohhot 010110, China;
3. Department of Genetics, Inner Mongolia Medical University, Hohhot 010110, China

Received:2015-06-08 Online:2016-03-28 Published:2016-03-31

摘要/Abstract

摘要：

目的: 探讨双酚A(BPA)对成年小鼠睾丸组织的损伤作用,阐明BPA对动物机体的生殖毒性及其作用机制。方法: 8周龄昆明小鼠40只随机分为对照组(玉米油)和低(100 mg·kg^-1 BPA)、中(200 mg·kg^-1BPA)、高(400 mg·kg^-1BPA)剂量BPA组。灌胃染毒4周后,取小鼠睾丸组织,采用流式细胞术检测小鼠睾丸组织中细胞凋亡率;免疫组织化学法检测Fas和FADD蛋白表达情况。结果: 与对照组比较,低剂量BPA组小鼠睾丸组织中细胞凋亡率、Fas和FADD阳性细胞表达率无明显变化(P>0.05);中和高剂量BPA组小鼠睾丸组织中细胞凋亡率、Fas和FADD阳性细胞表达率明显升高(P<0.05)。与低剂量BPA组比较,中和高剂量BPA组小鼠睾丸组织中细胞凋亡率、FAS和FADD阳性细胞表达率明显升高(P<0.05);与中剂量BPA组比较,高剂量BPA组小鼠睾丸组织中细胞凋亡率、FAS和FADD阳性细胞表达率明显升高(P<0.05)。中剂量BPA组细胞凋亡率与FAS、FADD阳性细胞表达率呈正相关关系(r=0.430,P<0.05;r=0.238,P<0.01),高剂量组细胞凋亡率与Fas、FADD阳性细胞表达率呈正相关关系(r=0.637,P<0.01;r=0.359,P<0.01)。结论: 一定剂量BPA会导致小鼠睾丸组织中细胞凋亡率升高,凋亡调控基因Fas和FADD表达上调;BPA对小鼠睾丸组织有损伤作用,其生殖毒性与激活Fas死亡受体信号通路从而导致细胞过度凋亡有关。

关键词: 双酚A, Fas蛋白, FADD蛋白, 细胞凋亡

Abstract:

Objective: To investigate the damage effect of bisphenol A (BPA) on the testis tissue of adult mice, and to reveal the reproductive toxicity of BPA in the body of animal and mechanism.Methods: 40 KM mice aged 8 weeks were randomly divided into control group (according to the weight ratio of corn oil gavage), low dose of BPA group (100 mg·kg^-1 BPA), moderate dose of BPA group (200 mg·kg^-1 BPA), and high dose of BPA group (400 mg·kg^-1 BPA).4 weeks laster, the testis tissue was taken.The apoptotic rates in the testis tissue were detected by flow cytometry; the distribution and expression of Fas and FADD were measured by immunohistochemistry.Results: Compared with control group, the apoptotic rate, the expression rates of Fas and FADD in testis tissue of the mice in low dose of BAP group had no changes (P>0.05), while the apoptotic rates in the testis tissue and the positive expressions rates of Fas and FADD in moderate and high doses of BPA groups were increased (P<0.05). Compared with low dose of BPA group, the apoptotic rates and the positive expression rates of FAS and FADD in tests tissue of the mice in moderate and high doses of BPA groups were significantly increased(P<0.05). Compared with moderate dose of BPA group, the apoptotic rate and the positive expression rates of FAS and FADD in testis tissue of the mice in high dose of BPA group was significantly increased (P<0.05).The overexpression of Fas and FADD was positively correlated to the apoptotic rate in testis tissue in moderate dose of BPA group (r=0.430, P<0.05; r=0.238, P<0.01) and high dose of BPA group (r=0.637, P<0.01; r=0.359, P<0.01).Conclusion: BPA with content dose can increase the apoptotic rates of cells in testis tissue and the expressions of Fas and FADD.BPA's reproductive toxicity may be closely associated with the activation of Fas signal pathway and resulting in massive apoptosis.

Key words: bisphenol A, factor associated suicide, Fas-associated death domain, apoptosis

中图分类号:

R321.1

郝兴霞, 张东泽, 于泊洋, 张岩, 周圆圆, 邱雪迎, 周好乐, 刘陶迪. 双酚A对成年雄性小鼠的生殖毒性及其作用机制[J]. 吉林大学学报(医学版), 2016, 42(02): 195-199.

HAO Xingxia, ZHANG Dongze, YU Boyang, ZHANG Yan, ZHOU Yuanyuan, QIU Xueying, ZHOU Haole, LIU Taodi. Reproductive toxicity of bisphenol A in adult male mice and mechanism[J]. Journal of Jilin University Medicine Edition, 2016, 42(02): 195-199.

参考文献

[1] Vandenberg LN,Chahoud I,Heindel JJ,et al.Urinary,circulating and tissue biomonitoring studies indicate wide-spread exposure to bisphenol A[J].Environ Health Perspect,2010,118(8):1055-1070.

[2] Zalko D,Jacques C,Duplan H,et al.Viable skin efficiently absorbs and metabolizes bisphenol A[J].Chemosphere,2011,82(3):424-430.

[3] 黄伯贤,覃莲菊,崔毓桂,等.双酚A在日常生活中的接触及其对人类生殖内分泌的干扰[J].生殖与避孕,2013,33(10):696-700.

[4] Rezg R,El-Fazaa S,Gharbi N,et al.Bisphenol A and human chronic diseases:current evidences,possible mechanisms,and future perspectives[J].Environ Int,2014,64(3):83-90.

[5] 王晓梅,洪燕,陈锋.中低剂量双酚A对小鼠肝、肾氧化损伤作用的实验研究[J].实用预防医学,2013,20(3):280-282.

[6] 李玉华,段斐,杨芬,等.青春期雄鼠BPA暴露对生殖功能及子代性别比的影响[J].生殖与避孕,2015,35(3):141-145.

[7] Kinch CD,Ibhazehiebo K,Jeong JH,et al.Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish[J].Proc Natl Acad Sci USA,2015,112(5):1475-1480.

[8] Chevalier N,Brucker-Davis F,Lahlou N,et al.A negative correlation between insulin-like peptide 3 and bisphenol A in human cord blood suggests an effect of endocrine disruptors on testicular descent during fetal development[J].Hum Reprod,2015,30(2):447-453.

[9] Guida M,Troisi J,Ciccone C,et al.Bisphenol A and congenital developmental defects in humans[J].Mutat Res,2015,774(8):33-39.

[10] Sharpe RM.Bisphenol A exposure and sexual dysfunction in men:editorial commentary on the article ‘Occupational exposure to bisphenol-A (BPA) and the risk of self-reported male sexual dysfunction,Li et al.,2009’[J].Hum Reprod,2010,25(2):292-294.

[11] Vandenberg LN,Colborn T,Hayes TB,et al.Hormones and endocrine-disrupting chemicals:low-dose effects and nonmonotonic dose responses[J].Endo Rev,2012,33(3):378-455.

[12] Bondesson M,Jonsson J,Pongratz I,et al.A CASCADE of effects of bisphenol A[J].Reprod Toxicol,2009,28(4):563-567.

[13] Sobarzo CM,Lustig L,Ponzio R,et al.Effect of di-(2-ethylhexyl) phthalate on N-cadherin and catenin protein expression in rat testis[J].Reprod Toxicol,2006,22(1):77-86.

[14] McClusky LM,de Jager C,Bornman MS.Stage-related increase in the proportion of apoptotic germ cells and altered frequencies of stages in the spermatogenic cycle following gestational,lactational,and direct exposure of male rats to p-nonylphenol[J].Toxicol Sci,2007,95(1):249-256.

[15] 鲍爱梅.FADD磷酸化对雄性小鼠精子发生影响的研究[D].南京:南京医科大学,2011:1-74.

双酚A对成年雄性小鼠的生殖毒性及其作用机制

Reproductive toxicity of bisphenol A in adult male mice and mechanism

RichHTML

PDF (PC)

赞

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	朱德强, 陈学军. 白花丹素对肝癌索拉菲尼耐药细胞HepG2R增殖和凋亡的影响及其机制[J]. 吉林大学学报(医学版), 2018, 44(06): 1223-1229.
[2]	阎慧, 马淑飞, 段明华, 闫玉礼, 潘新, 李海清, 周长龙, 赵天倚. 京尼平对胃癌SGC 7901细胞体外增殖、侵袭能力和凋亡的影响及其机制[J]. 吉林大学学报(医学版), 2018, 44(05): 924-928.
[3]	邢树刚, 张丽红, 金明华, 李百慧, 武则馨, 房波, 李伟. 杨梅黄酮对小鼠脑胶质瘤GL261细胞增殖和凋亡的影响[J]. 吉林大学学报(医学版), 2018, 44(05): 955-961.
[4]	薛亚娟, 符兆英. 人乳头瘤病毒致癌特性及其E6和E7蛋白致癌机制的研究进展[J]. 吉林大学学报(医学版), 2018, 44(05): 1096-1099.
[5]	于洋, 徐路, 刘师兵, 李松岩, 徐冶. 杨梅素通过促进DRP1依赖性线粒体分裂诱导人卵巢癌SKOV3细胞凋亡[J]. 吉林大学学报(医学版), 2018, 44(05): 903-907.
[6]	王淼, 母润红, 李明成, 李洪杰. RNAi沉默survivin和HIF-1α基因对胃癌BGC-823细胞体外增殖和凋亡的影响[J]. 吉林大学学报(医学版), 2018, 44(04): 753-758.
[7]	杨万霞, 苏强, 邢爱华, 张晓延. 饥饿对Beclin-1依赖的Ana-1细胞自噬和凋亡的影响[J]. 吉林大学学报(医学版), 2018, 44(04): 704-708.
[8]	朱效慧, 孟琴, 冯世燕. TP53在不明原因复发性流产患者绒毛组织中的表达及其对人滋养层细胞生长的影响[J]. 吉林大学学报(医学版), 2018, 44(04): 796-800.
[9]	王娟, 刘文龙, 赵苒, 范春. 双酚A联合己烯雌酚对未成年雌性SD大鼠的雌激素效应[J]. 吉林大学学报(医学版), 2018, 44(04): 731-735.
[10]	安乐, 杨建征, 胡春梅, 于琼, 肖晗, 郝书弘, 唐艳. 多囊蛋白1基因对人宫颈癌HeLa细胞的抗凋亡作用[J]. 吉林大学学报(医学版), 2018, 44(04): 776-779.
[11]	吕鹏, 宁明杰, 邵玉, 张璐妮, 唐英, 王南博, 陈飞儿, 齐玲. 野黄芩苷对人脑胶质瘤U87细胞的增殖抑制作用及其机制[J]. 吉林大学学报(医学版), 2018, 44(03): 466-470.
[12]	杨文延, 刘强, 孙志娟, 杜利清, 徐畅, 王彦, 柳杨, 王芹. 褪黑素对人非小细胞肺癌H1299细胞辐射敏感性的影响[J]. 吉林大学学报(医学版), 2018, 44(03): 532-536.
[13]	任艳芳, 姜永杰, 张秀玲, 姜姗, 王玉红. SHH信号通路对子痫前期患者滋养细胞凋亡和侵袭的影响及其机制[J]. 吉林大学学报(医学版), 2018, 44(03): 510-515.
[14]	丁振东, 张玉影, 张宇, 钟越, 温娜, 于洪泉, 齐玲. 五味子多糖对脑肿瘤干细胞的凋亡诱导及生长抑制作用[J]. 吉林大学学报(医学版), 2018, 44(02): 305-309.
[15]	杨易, 包康达, 周彦兵, 袁超, 李勇, 刘晓明, 徐金瑞. Wnt5a对人肺腺癌A549细胞凋亡的调控作用及其机制[J]. 吉林大学学报(医学版), 2018, 44(02): 229-234.