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      Effects of endocrine disrupting chemicals on expression of phospholipidhydroperoxide glutathione peroxidase mRNA in rat testes

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      https://www.riss.kr/link?id=A104763766

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      다국어 초록 (Multilingual Abstract)

      Phospholipid hydroperoxide glutathione peroxidase (PHGPx), an antioxidative selenoprotein, is modulated by estrogen in the testis and oviduct. To examine whether potential endocrine disrupting chemicals (EDCs) affect the microenvironment of the testes, the expression patterns of PHGPx mRNA and histological changes were analyzed in 5-week-old Sprague-Dawley male rats exposed to several EDCs such as an androgenic compound [testosterone (50, 200, and 1,000 μg/kg)], anti-androgenic compounds [flutamide (1, 5, and 25 mg/kg), ketoconazole (0.2 and 1 mg/kg), and diethylhexyl phthalate (10, 50, and 250 mg/kg)], and estrogenic compounds [nonylphenol (10, 50, 100, and 250 mg/kg), octylphenol (10, 50, and 250 mg/kg), and diethylstilbestrol (10, 20, and 40 μg/kg)] daily for 3 weeks via oral administration. Mild proliferation of germ cells and hyperplasia of interstitial cells were observed in the testes of the flutamide-treated group and deletion of the germinal epithelium and sloughing of germ cells were observed in testes of the diethylstilbestrol-treated group. Treatment with testosterone was shown to slightly decrease PHGPx mRNA levels in testes by the reverse transcriptionpolymerase chain reaction. However, anti-androgenic compounds (flutamide, ketoconazole, and diethylhexyl phthalate) and estrogenic compounds (nonylphenol, octylphenol, and diethylstilbestrol) significantly upregulated PHGPx mRNA in the testes (p < 0.05). These findings indicate that the EDCs might have a detrimental effect on spermatogenesis via abnormal enhancement of PHGPx expression in testes and that PHGPx is useful as a biomarker for toxicity screening of estrogenic or antiandrogenic EDCs in testes.
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      Phospholipid hydroperoxide glutathione peroxidase (PHGPx), an antioxidative selenoprotein, is modulated by estrogen in the testis and oviduct. To examine whether potential endocrine disrupting chemicals (EDCs) affect the microenvironment of the testes...

      Phospholipid hydroperoxide glutathione peroxidase (PHGPx), an antioxidative selenoprotein, is modulated by estrogen in the testis and oviduct. To examine whether potential endocrine disrupting chemicals (EDCs) affect the microenvironment of the testes, the expression patterns of PHGPx mRNA and histological changes were analyzed in 5-week-old Sprague-Dawley male rats exposed to several EDCs such as an androgenic compound [testosterone (50, 200, and 1,000 μg/kg)], anti-androgenic compounds [flutamide (1, 5, and 25 mg/kg), ketoconazole (0.2 and 1 mg/kg), and diethylhexyl phthalate (10, 50, and 250 mg/kg)], and estrogenic compounds [nonylphenol (10, 50, 100, and 250 mg/kg), octylphenol (10, 50, and 250 mg/kg), and diethylstilbestrol (10, 20, and 40 μg/kg)] daily for 3 weeks via oral administration. Mild proliferation of germ cells and hyperplasia of interstitial cells were observed in the testes of the flutamide-treated group and deletion of the germinal epithelium and sloughing of germ cells were observed in testes of the diethylstilbestrol-treated group. Treatment with testosterone was shown to slightly decrease PHGPx mRNA levels in testes by the reverse transcriptionpolymerase chain reaction. However, anti-androgenic compounds (flutamide, ketoconazole, and diethylhexyl phthalate) and estrogenic compounds (nonylphenol, octylphenol, and diethylstilbestrol) significantly upregulated PHGPx mRNA in the testes (p < 0.05). These findings indicate that the EDCs might have a detrimental effect on spermatogenesis via abnormal enhancement of PHGPx expression in testes and that PHGPx is useful as a biomarker for toxicity screening of estrogenic or antiandrogenic EDCs in testes.

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      참고문헌 (Reference)

      1 "the fungicide vinclozolinalters sex differentiation of the male rat. Toxicol ApplPharmacol 1994" 46-52,

      2 "accumulation of toxic metabolites fromnonionic surfactants. Science 1984" 623-625,

      3 "Tissue-specific functions of individualglutathione peroxidases" 27 : 951-965, 1999

      4 "The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat" 58 : 339-349, 2000

      5 "Testosteronemediates expression of the selenoprotein PHGPx by inductionof spermatogenesis and not by direct transcriptional geneactivation" 12 : 1359-1370, 1998

      6 "Quantitative changes in gene expression in fetalrat testes following exposure to di(n-butyl) phthalate" 73 : 431-441, 2003

      7 "Pesticides: multiple mechanisms of demasculinization" 126 : 1-5, 1997

      8 "Perreau C. Effects of flutamide or of supplementation withtestosterone in prepubertal male rats prenatally treated withbusulfan. Acta Endocrinol" 550-557, 1985

      9 "Murine phospholipid hydroperoxideglutathione peroxidase: cDNA sequence, tissue expression,and mapping" 10 : 601-605, 1999

      10 "Maternal oestrogen/ xenoestrogen exposure alters expression of steroidogenic factor-1 (SF-1/Ad4BP) in the fetal rat testis" 127 : 91-98, 1997

      1 "the fungicide vinclozolinalters sex differentiation of the male rat. Toxicol ApplPharmacol 1994" 46-52,

      2 "accumulation of toxic metabolites fromnonionic surfactants. Science 1984" 623-625,

      3 "Tissue-specific functions of individualglutathione peroxidases" 27 : 951-965, 1999

      4 "The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat" 58 : 339-349, 2000

      5 "Testosteronemediates expression of the selenoprotein PHGPx by inductionof spermatogenesis and not by direct transcriptional geneactivation" 12 : 1359-1370, 1998

      6 "Quantitative changes in gene expression in fetalrat testes following exposure to di(n-butyl) phthalate" 73 : 431-441, 2003

      7 "Pesticides: multiple mechanisms of demasculinization" 126 : 1-5, 1997

      8 "Perreau C. Effects of flutamide or of supplementation withtestosterone in prepubertal male rats prenatally treated withbusulfan. Acta Endocrinol" 550-557, 1985

      9 "Murine phospholipid hydroperoxideglutathione peroxidase: cDNA sequence, tissue expression,and mapping" 10 : 601-605, 1999

      10 "Maternal oestrogen/ xenoestrogen exposure alters expression of steroidogenic factor-1 (SF-1/Ad4BP) in the fetal rat testis" 127 : 91-98, 1997

      11 "Loriaux DL. The effect ofketoconazole on steroidogenesis I. Leydig cell enzymeactivity in vitro. Res Commun Chem Pathol Pharmacol 1988" 17-26,

      12 "Localization of oestrogen receptor α, oestrogen receptor β and androgen receptors in the rat reproductive organs" 165 : 359-370, 2000

      13 "Inhibition of steroidogenesis by ketoconazole. Therapeuticuses" 58 : 494-502, 1997

      14 "Hypospadias and endocrine disruption: is there a connection?" 109 : 1175-1183, 2001

      15 "How strong is the evidence of a link between environmental chemicals and adverse effects on human reproductive health?" 328 : 447-451, 2004

      16 "Girotti AW. Protectiveaction of phospholipid hydroperoxide glutathione peroxidaseagainst membrane-damaging lipid peroxidation. In situreduction of phospholipid and cholesterol hydroperoxides. JBiol Chem 1990" maiori (maiori): 454-461,

      17 "Expression pattern of phospholipid hydroperoxideglutathione peroxidase messenger ribonucleic acid in mouse testis" 58 : 1272-1276, 1998

      18 "Expression of human phospholipid hydroperoxide glutathione peroxidase gene for protection of host cells from lipid hydroperoxide-mediated injury" 219 : 486-491, 1996

      19 "Estrogen selectively up-regulates the phospholipid hydroperoxideglutathione peroxidase in the oviducts" 146 : 2583-2592, 2005

      20 "Estrogen receptor-α mediates thedetrimental effects of neonatal diethylstilbestrol exposure in the murine reproductive tract" 205 : 55-63, 2004

      21 "Estrogen receptor-alpha knockout mice exhibitresistance to the developmental effects of neonataldiethylstilbestrol exposure on the female reproductive tract" 238 : 224-238, 2001

      22 "Estrogen imprinting of the developing prostate gland is mediated through stromal estrogen receptor alpha:studies with αERKO and βERKO mice" 61 : 6089-6097, 2001

      23 "Environmental anti-androgens^malereproductive health focus on phthalates and testiculardysgenesis syndrome" 127 : 305-315, 2004

      24 "Effects of 17β-estradiol and tamoxifen on the selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA expression in male reproductive organs of rats" 49 : 389-396, 2003

      25 "Disruption of androgen-regulated male reproductive development by di(n-butyl) phthalate during late gestation in rats is different from flutamide" 156 : 81-95, 1999

      26 "Differential expression of 3 ß-hydroxysteroid dehydrogenase mRNA in rat testes exposed to endocrine disruptors" 53 : 465-471, 2007

      27 "Di(n-butyl) phthalate impairs cholesterol transport and steroidogenesis in the fetal rat testis through a rapid and reversible mechanism" 145 : 1227-1237, 2004

      28 "Chronic administration of 4-tertoctylphenolto adult male rats causes shrinkage of the testesand male accessory sex organs, disrupts spermatogenesis,and increases the incidence of sperm deformities" 57 : 267-277, 1997

      29 "Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) inmammalian cells" 34 : 145-169, 2003

      30 "Anenvironmental antiandrogen, vinclozolin, alters the organization of play behavior" 79 : 151-156, 2003

      31 "Alterations of gene expression in adult male rat testis and pituitary shortly after subacute administration of the antiandrogen flutamide" 49 : 275-290, 2003

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      2023 평가예정 해외DB학술지평가 신청대상 (해외등재 학술지 평가)
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      2006-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2005-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 1.08 0.11 0.76
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.61 0.51 0.245 0.05
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