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2020, 04, v.29 522-527
溴氰菊酯对大鼠卵巢甾体激素合成的影响
基金项目(Foundation): 中国医学科学院医学与健康科技创新工程项目资助(2018-I2M-1-004);; 中央级公益性科研院所基本科研业务项目(2019GJZ03)
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摘要:

目的探讨溴氰菊酯(Deltamethrin,DLT)对大鼠卵巢甾体激素合成的影响及相关的分子机制。方法不同剂量DLT暴露处理大鼠和原代颗粒细胞;取DLT暴露后的大鼠血清和培养上清液,电化学发光法测定雌二醇和孕酮的水平;Western Blot法检测DLT暴露后大鼠卵巢组织及原代培养颗粒细胞中甾体激素合成关键酶:甾体激素合成急性调节蛋白(StAR)、胆固醇侧链裂解酶(P450scc)、芳香化酶的表达量,同时检测组蛋白去乙酰化酶Sirt1的蛋白表达。结果体、内外实验中,DLT各处理组大鼠血清、原代颗粒细胞培养上清液中雌二醇水平均显著升高(体内实验P<0.05,体外实验P<0.001);体内实验中DLT各处理组大鼠血清孕酮水平均显著降低(P<0.05),而体外实验中DLT各处理组原代颗粒细胞培养上清液孕酮水平无显著变化(P>0.05);体、内外实验中DLT各处理组大鼠卵巢组织、原代培养颗粒细胞中StAR、P450scc、芳香化酶以及Sirt1的表达量均显著升高(P<0.01)。结论 DLT能影响大鼠卵巢雌二醇和孕酮的合成,其机制可能与其关键酶表达的变化有关。

Abstract:

Objective:To explore the effects and related molecular mechanisms of deltamethrin(DLT)on ovarian steroidogenesis in rats.Methods:Sprague-Dawley rats and primary cultures of rat granulosa cells were treated with different doses of DLT. The levels of estradiol and progesterone in DLT-treated rat serum or granulosa cell culture supernatant were determined by electrochemiluminescence immunoassay. The expression of key enzymes related with steroid hormone synthesis:steroidogenic acute regulatory protein(StAR),cytochrome P450 scc enzyme(P450 scc)and aromatase,as well as the expression of sirtuin 1(Sirt1)in DLT-treated rat ovary tissues or cultured rat granulosa cells were detected by Western Blot.Results:Both in vivo and in vitro experiments showed that the estradiol levels in rat serum or primary granulocyte culture supernatants were significantly increased in each DLT treatment group(P<0.05 in vivo,P<0.001 in vitro). DLT treatment decreased the progesterone level in vivo(P<0.05),but did not significantly change the level of progesterone in vitro(P>0.05). Both in vivo and in vitro experiments showed that the expression of StAR,P450 scc,aromatase and Sirt1 in DLT-treated rat ovary tissues or cultured rat granulosa cells were all significantly increased(P<0.01).Conclusions:DLT can affect estradiol and progesterone production of rat ovary,and the mechanism may be associated with the change of gene expression of key enzymes.

参考文献

[1] Richards JS.Perspective:the ovarian follicle-a perspectie in 2001[J].Endocrinology,2001,142:2184-2193.

[2] Mlynarcíková A,Kolena J,Ficková M,et al.Alterations in steroid hormone production by porcine ovarian granulosa cells caused by bisphenol A and bisphenol A dimethacrylate[J].Mol Cell Endocrinol,2005,244:57-62.

[3] Rodgers RJ,Irvingrodgers HF.Formation of the ovarian follicular antrum and follicular fluid1[J].Biol Reprod,2010,82:1021-1029.

[4] Senthilkumaran B,Yoshikuni M,Nagahama Y.A shift in steroidogenesis occurring in ovarian follicles prior to oocyte maturation[J].Mol Cell Endocrinol,2004,215:11-18.

[5] Craig ZR,Wang W,Flaws JA.Endocrine-disrupting chemicals in ovarian function:effects on steroidogenesis,metabolism and nuclear receptor signaling[J].Reproduction,2011,142:633-646.

[6] Piasek M,Blanu?a M,Kostial K,et al.Placental cadmium and progesterone concentrations in cigarette smokers[J].Reprod Toxicol,2001,15:673-681.

[7] Parker KL,Schimmer BP.Transcriptional Regulation of the Genes Encoding the Cytochrome P-450 Steroid Hydroxylases[J].Vitam Horm,1995,51:339-370.

[8] Luuthe V.Analysis and characteristics of multiple types of human 17beta-hydroxysteroid dehydrogenase[J].J Steroid Biochem Mol Biol,2001,76:143-151.

[9] Mindnich R,M?ller G,Adamski J.The role of 17 beta-hydroxysteroid dehydrogenases[J].Mol Cell Endocrinol,2004,218:7-20.

[10] Morita Y,Wada-Hiraike O,Yano T,et al.Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells:an implicative role of SIRT1 in the ovary[J].Reprod Biol Endocrinol,2012,10:14.

[11] 陈雨露.SIRT1在多囊卵巢综合征中的作用及机制研究[D].郑州:郑州大学,2017.

[12] Safe SH,Pallaroni L,Yoon K,et al.Toxicology of environmental estrogens[J].Reprod Fertil Dev,2001,13:307-315.

[13] Liu J,Yang Y,Zhuang S,et al.Enantioselective endocrine-disrupting effects of bifenthrin on hormone synthesis in rat ovarian cells[J].Toxicology,2011,290:42-49.

[14] Chen J,Chen H,Liu R,et al.Effects of fenvalerate on progesterone production in cultured rat granulosa cells[J].Reprod Toxicol,2005,20:195-202.

[15] Liu J,Yang Y,Yang Y,et al.Disrupting effects of bifenthrin on ovulatory gene expression and prostaglandin synthesis in rat ovarian granulosa cells[J].Toxicology,2011,282:47-55.

[16] Camargo-Mathias MI,Pereira NRC,Camila DSR,et al.Deltamethrin as inductor agent of precocious ovarian degeneration in Rhipicephalus sanguineuss.l.(Acari:Ixodidae)ticks[J].Exp Appl Acarol,2017,72:161-169.

[17] Ge LQ,Hu JH,Wu JC,et al.Insecticide-induced changes in protein,RNA,and DNA contents in ovary and fat body of female Nilaparvata lugens(Hemiptera:Delphacidae)[J].J Econ Entomol,2009,102:1506-1514.

[18] Bouwman H,Sereda B,Meinhardt HM.Simultaneous presence of DDT and pyrethroid residues in human breast milk from a malaria endemic area in South Africa[J].Environ Pollut,2006,144:902-917.

[19] Ding R,Cao Z,Wang Y,et al.The implication of p66shc in oxidative stress induced by deltamethrin[J].Chem Biol Interact,2017,278:162-169.

[20] Yu HM,Wu Y,Ju P,et al.eNOS-JNK1-AR signaling pathway mediates deltamethrin-induced germ cells apoptosis in testes of adult rats[J].Environ Toxicol Pharmacol,2014,38:733-741.

[21] Singh R,Jan M,Sharma P.Dose-dependent effect of deltamethrin in testis,liver,and Kidney of wistar rats[J].Toxicol Int,2014,21:131-139.

[22] Kilian E,Delport R,Bornman MS,et al.Simultaneous exposure to low concentrations of dichlorodiphenyltrichloroethane,deltamethrin,nonylphenol and phytoestrogens has negative effects on the reproductive parameters in male Spraque-Dawley rats[J].Andrologia,2010,39:128-135.

[23] Nimrod A.Studies on the synergistic effect of androgen on the stimulation of progestin secretion by fsh in cultured rat granulosa cells:Progesterone metabolism and the effect of androgens[J].Mol Cell Endocrinol,1977,8:189-199.

[24] Crellin N.Inhibition of basal and stimulated progesterone synthesis by dichlorodiphenyldichloroethylene and methoxychlor in a stable pig granulosa cell line[J].Reproduction,2001,121:485-492.

[25] Chen W,Yang X,Wang B,et al.The effects and possible mechanisms of triclosan on steroidogenesis in primary rat granulosa cells[J].Reprod Toxicol,2019,83:28-37.

[26] Reverchon M,Rame C,Bunel A,et al.VISFATIN(NAMPT)Improves In Vitro IGF1-Induced Steroidogenesis and IGF1 Receptor Signaling Through SIRT1 in Bovine Granulosa Cells[J].Biol Reprod,2016,94:1-19.

[27] Han Y,Luo H,Wang H,et al.SIRT1 induces resistance to apoptosis in human granulosa cells by activating the ERK pathway and inhibiting NF-κB signaling with anti-inflammatory functions[J].Apoptosis,2017,22:1260-1272.

[28] Vorherr H.Fibrocystic breast disease:Pathophysiology,pathomorphology,clinical picture,and management[J].Am J Obstet Gynecol,1986,154:161-179.

[29] Chobanyan NS.Re:Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women[J].J Natl Cancer Inst,1999,91:724-725.

[30] Ho SM.Estrogen,progesterone and epithelial oarian cancer[J].Reprod Biol Endocrinol,2003,1:73.

[31] Lukanova A,Lundin E,Micheli A,et al.Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women[J].Int J Cancer,2004,108:425-432.

基本信息:

中图分类号:R994.6

引用信息:

[1]刘晨晨,骆海燕,郐艳荣,等.溴氰菊酯对大鼠卵巢甾体激素合成的影响[J].生殖医学杂志,2020,29(04):522-527.

基金信息:

中国医学科学院医学与健康科技创新工程项目资助(2018-I2M-1-004);; 中央级公益性科研院所基本科研业务项目(2019GJZ03)

投稿时间:

2019-11-27

投稿日期(年):

2019

终审时间:

2020-02-26

终审日期(年):

2020

修回时间:

2019-12-30

审稿周期(年):

1

发布时间:

2020-04-15

出版时间:

2020-04-15

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