(18.210.12.229) 您好!臺灣時間:2021/03/03 16:05
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:連柏鈞
研究生(外文):Po-ChunLien
論文名稱:男性成人鄰苯二甲酸酯暴露對芳香轉化酶之影響探討
論文名稱(外文):The effects of phthalate exposure on aromatase expression in adult men
指導教授:李俊璋李俊璋引用關係
指導教授(外文):Ching-Chang Lee
學位類別:碩士
校院名稱:國立成功大學
系所名稱:環境醫學研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:中文
論文頁數:127
中文關鍵詞:鄰苯二甲酸酯類男性不孕生殖荷爾蒙芳香轉化酶健康風險評估
外文關鍵詞:phthalate estersmale infertilityreproductive hormonesaromatasehealth risk assessment
相關次數:
  • 被引用被引用:2
  • 點閱點閱:92
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:1
近年來研究指出,成年男性體內睪固酮濃度與精液品質皆有逐年下降的趨勢,可能造成生育率的降低甚至不孕症(infertility)。在不孕症案例中因男性因素導致不孕者約佔30-50%,其危險因子包括生理(年齡、BMI)、心理(情緒壓力)、基因(種族)、生活習慣(抽菸、飲酒、個人衛生用品使用)或環境毒物暴露等因素。環境因子中鄰苯二甲酸酯(Phthalate esters, PAEs)已被證實為內分泌干擾物質,具低揮發性、低蒸氣壓及高脂溶性等特性,常用於日常生活塑膠製品及個人衛生用品。動物研究指出PAEs會透過抗雄性激素及雌激素之毒性效應導致動物之生長發育等生殖危害,包括睪丸缺陷症候群、生殖荷爾蒙失調、精液品質降低、睪丸癌等。人類流行病學研究結果,顯示暴露PAEs可能會導致生殖荷爾蒙改變及精液品質降低,其中芳香轉化酶(Aromatase)為生殖荷爾蒙調控中參與雄激素轉換成雌激素反應之重要酵素,能影響雌激素代謝與精子生成。然而,目前研究關於PAEs暴露對體內aromatase活性之影響尚無定論,而人類流行病學研究對於aromatase活性目前多利用睪固酮與雌二醇之比值(T/E2)表示,並未有實際量測aromatase濃度之結果。綜上可知,目前對於PAEs暴露是否影響人體aromatase之研究付之闕如,且其機制亦不明確。因此,本研究擬探討男性成人PAEs暴露對體內aromatase之影響機制。本研究自國立成功大學附設醫院及安安婦幼中心不孕症門診共招募298位研究對象,包含259位不孕男性及39位具生育力男性,經簽屬同意書後,進行標準化之問卷調查、血液及尿液樣本採集,並分析血液中生殖荷爾蒙與aromatase濃度、尿液PAEs代謝物濃度,整合相關研究數據後探討生殖荷爾蒙濃度、尿液PAEs代謝物濃度以及aromatase濃度之相關性,以評估男性成人PAEs暴露對aromatase之影響。研究對象共區分為具生育力男性、不孕且精液品質正常男性及不孕且精液品質異常男性三組,結果顯示不孕且精液品質異常之男性成人尿液中MMP (3.00 vs. 3.48 vs. 3.59)、MEP (10.6 vs. 13.6 vs.15.3)、MiBP(6.00 vs. 5.93 vs. 6.98)、 MEHHP (9.54 vs. 10.2 vs. 10.5)、MECPP(12.3 vs. 12.9 vs. 14.1)、MEOHP(6.64 vs. 7.06 vs. 7.69)、MINP(0.12 vs. 0.22 vs. 0.26)及MIDP(0.13 vs. 0.20 vs.0.23)幾何平均濃度(µg/g-cre)皆高於不孕且精液品質正常男性及具生育力男性成人。其中,尿液中MINP濃度達統計上顯著差異(P=0.013)。血液中生殖荷爾蒙分析結果顯示,不孕且精液品質異常男性體內E2濃度顯著高於不孕且精液品質正常男性及具生育力男性,且三組呈顯著趨勢相關(Ptrend=0.001)。血液中aromatase濃度分析結果,不孕且精液品質異常男性體內aromatase濃度顯著高於不孕且精液品質正常男性及具生育力男性(P=0.001),且三組呈顯著趨勢相關(Ptrend=0.004)。經校正年齡、BMI及抽血季節後,以迴歸分析結果顯示尿液中MMP、MEP及MEOHP濃度與E2濃度呈顯著正相關;尿液中MMP和MEP濃度與TT/E2呈顯著負相關;尿液中MiBP、MnBP、MEHHP、MECPP、MEOHP濃度與aromatase濃度呈顯著正相關,尿液中MEP及MEHP濃度與aromatase濃度呈邊緣顯著正相關(P〈0.1)。由以上證據得知,男性成人暴露PAEs後,可能會增加體內aromatase濃度,進而促使TT轉化為E2,並可能與雌激素受體結合,干擾雌激素受體調控CYP19a1 gene,直接或間接導致男性成人體內E2濃度異常增加。此外,進一步估算PAEs對雌激素受體及雄激素受體之結合效應及拮抗效應指標,發現不孕男性於雄激素受體拮抗效應指標及雌激素受體結合能力效應指標均有較高情形,顯示PAEs可能透過與雌激素受體結合及拮抗雄激素受體之效應影響內分泌系統之正常運作。最後以尿液中PAEs濃度及參考劑量進行男性成人健康風險評估,在PAEs暴露對於生殖及發育、肝臟危害結果危害指標HI值均小於1,顯示目前針對PAEs之生殖危害所訂定之參考劑量仍有檢討之必要,可能需再降低之。
The objectives of present study are to assess the associations among urinary phthalate metabolites levels, reproductive hormones and serum aromatase concentrations in adult men, and to explore the active mechanisms of phthalate exposure on aromatase expression in adult men. Two hundred and ninety eight subjects were recruited from the infertile clinic of National Cheng Kung University Hospital (NCKUH) and AN-AN Women and Children Clinic, including two hundred and fifty nine infertile men and thirty nine fertile men. After signed informed consent, the present study conducted through the questionnaire interview, determination of reproductive hormones, aromatase, and urinary phthalate metabolites. Urinary phthalate metabolites were analyzed with HPLC-MS/MS. Serum aromatase concentrations were determined by enzyme-linked immunosorbent assay. Urinary MMP (3.00 vs. 3.48 vs. 3.59 µg/g-cre), MEP (10.6 vs. 13.6 vs.15.3), MiBP (6.00 vs. 5.93 vs. 6.98), MEHHP (9.54 vs. 10.2 vs. 10.5), MECPP (12.3 vs. 12.9 vs. 14.1), MEOHP (6.64 vs. 7.06 vs. 7.69), MINP(0.12 vs. 0.22 vs. 0.26)and MIDP (0.13 vs. 0.20 vs.0.23) in infertile men with abnormal semen quality were higher than infertile men with normal semen quality and fertile men. Urinary MINP showed significant difference among three groups(P=0.013). Estradiol and serum aromatase concentrations in infertile men with abnormal semen quality were significant higher than infertile men with normal semen quality and fertile men(P=0.006, 0.001)respectively. The significant increasing trends were found in estradiol levels and serum aromatase concentrations among the three groups(Ptrend=0.001, 0.004)respectively. After adjusting for age, BMI and season of blood drawing, urinary MMP, MEP and MEOHP were significantly positively associated with estradiol. Urinary MMP and MEP were significantly negatively associated with the TT:E2 ratio. Urinary MiBP, MnBP, MEHHP, MECPP, MEOHP were significantly positively associated with serum aromatase concentrations. The infertile men with abnormal semen quality had higher estrogen receptor binding effect and androgen receptor antagonistic effect than infertile men with normal semen quality and fertile men. Risk assessment of phthalate exposure on reproduction and liver effects showed that all hazard index were below 1, suggesting that it is necessary to reassess the value of reference dose. In conclusion, phthalate exposure may increase serum aromatase concentrations, upregulation of CYP19a1 gene for the estrogen receptors, resulting in abnormally increase of estradiol levels by an estrogenic mode of action.
摘要 I
Extended Abstract III
致謝 VI
目錄 VIII
表目錄 XI
圖目錄 XIII
第一章 緒論 1
1-1 研究背景 1
1-2 研究目的 4
1-3 研究重要性 4
第二章 文獻回顧 5
2-1 雄性生殖與不孕症 5
2-1-1 雄性生殖系統 5
2-1-2 荷爾蒙調控與精子生成 5
2-1-3男性不孕症之定義及診斷 7
2-1-4男性不孕症之危險因子 8
2-1-5芳香轉化酶(Aromatase)與雄性生殖 8
2-1-5-1 Aromatase與CYP19基因 8
2-1-5-2 Aromatase與生殖荷爾蒙調控機制 9
2-1-5-3 Aromatase與精子生成及凋亡(apoptosis) 10
2-1-5-4人類流行病學研究 12
2-2 PAEs之暴露及代謝 12
2-2-1 PAEs之物化特性 12
2-2-2 PAEs之暴露途徑 13
2-2-3人體之PAEs代謝機制 14
2-3不孕與一般男性族群尿液中PAEs代謝物濃度調查研究 15
2-4 PAEs暴露對生殖荷爾蒙分泌回饋機制之影響 18
2-4-1細胞及動物實驗 18
2-4-2流行病學調查研究 19
2-5 PAEs暴露對芳香轉化酶(Aromatase)之影響 22
2-5-1細胞及動物實驗 22
2-5-2流行病學調查研究 24
第三章 材料與方法 26
3-1 研究架構 26
3-2 研究對象選取流程 26
3-3 男性成人環境中PAEs暴露來源及生活品質調查評估之標準化問卷 27
3-4 樣本採集方法 29
3-4-1血液樣本採集 29
3-4-2尿液樣本採集 29
3-5 樣本分析方法 29
3-5-1血液中生殖荷爾蒙濃度分析 29
3-5-2血液中芳香轉化酶(Aromatase)濃度分析 30
3-5-3尿液中PAEs代謝物濃度分析 31
3-6男性成人PAEs日暴露劑量推估 35
3-7 PAEs與雌激素受體及雄激素受體之效應評估 36
3-8健康風險評估 37
3-9 統計分析方法 37
第四章 結果與討論 39
4-1 男性成人環境中PAEs暴露來源及生活品質調查評估之標準化問卷結果解析 39
4-1-1男性成人之基本資料分布情形 39
4-1-2男性成人之生活習慣情形 40
4-1-3男性成人之家戶環境及建材調查結果 41
4-1-4男性成人之身心健康狀態分析結果 41
4-1-5男性成人之生殖健康狀態分析結果 42
4-1-6男性成人之個人衛生用品使用情形分析結果 42
4-1-7男性成人日常飲食使用塑膠用品習慣調查結果 43
4-1-8男性成人之飲食攝取習慣調查結果 44
4-1-9男性成人之外食塑膠用品使用習慣調查結果 45
4-1-10男性成人之五大類食品攝取量調查結果 46
4-2 男性成人血清中生殖荷爾蒙濃度分析結果 47
4-2-1血清中生殖荷爾蒙濃度分布情形 47
4-2-2血清中生殖荷爾蒙濃度之差異 47
4-3 男性成人尿液中PAEs代謝物濃度分析結果 48
4-3-1品保及品管執行結果 48
4-3-2尿液中PAEs代謝物濃度分析結果 49
4-3-3尿液中PAEs代謝物濃度差異 50
4-4 男性成人血液中Aromatase濃度分析結果 51
4-4-1品保及品管執行結果 51
4-4-2血液中Aromatase濃度分析結果 51
4-5 PAEs暴露源與尿液中PAEs代謝物濃度之相關性分析 52
4-6血液中生殖荷爾蒙與Aromatase濃度之相關性分析 55
4-7血液中生殖荷爾蒙、Aromatase濃度與尿液中PAEs代謝物濃度之相關性分析 56
4-8 PAEs暴露與雌激素受體結合能力效應指標及雄激素受體拮抗效應指標分析 59
4-9 PAEs暴露健康風險評估 60
第五章 結論與建議 63
5-1 結論 63
5-2 建議 65
第六章 參考文獻 66
Adibi JJ, Perera FP, Jedrychowski W, Camann DE, Barr D, Jacek R, et al. 2003. Prenatal exposures to phthalates among women in New York City and Krakow, Poland. Environ Health Perspect 111: 1719-22.
Akingbemi BT, Ge R, Klinefelter GR, Zirkin BR, Hardy MP. 2004. Phthalate-induced Leydig cell hyperplasia is associated with multiple endocrine disturbances. Proc Natl Acad Sci U S A 101: 775-80.
Akingbemi BT, Youker RT, Sottas CM, Ge R, Katz E, Klinefelter GR, et al. 2001. Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl)phthalate. Biol Reprod 65: 1252-9.
Andrade AJ, Grande SW, Talsness CE, Gericke C, Grote K, Golombiewski A, et al. 2006. A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): reproductive effects on adult male offspring rats. Toxicology 228: 85-97.
Aquila S, Sisci D, Gentile M, Middea E, Catalano S, Carpino A, et al. 2004. Estrogen receptor (ER)alpha and ER beta are both expressed in human ejaculated spermatozoa: evidence of their direct interaction with phosphatidylinositol-3-OH kinase/Akt pathway. J Clin Endocrinol Metab 89: 1443-51.
Aquila S, Sisci D, Gentile M, Middea E, Siciliano L, Ando S. 2002. Human ejaculated spermatozoa contain active P450 aromatase. J Clin Endocrinol Metab 87: 3385-90.
Berman T, Hochner-Celnikier D, Calafat AM, Needham LL, Amitai Y, Wormser U, et al. 2009. Phthalate exposure among pregnant women in Jerusalem, Israel: results of a pilot study. Environ Int 35: 353-7.
Bhatia H, Kumar A, Ogino Y, Gregg A, Chapman J, McLaughlin MJ, et al. 2014. Di-n-butyl phthalate causes estrogenic effects in adult male Murray rainbowfish (Melanotaenia fluviatilis). Aquat Toxicol 149: 103-15.
Blount BC, Silva MJ, Caudill SP, Needham LL, Pirkle JL, Sampson EJ, et al. 2000. Levels of seven urinary phthalate metabolites in a human reference population. Environ Health Perspect 108: 979-82.
Bois C, Delalande C, Nurmio M, Parvinen M, Zanatta L, Toppari J, et al. 2010. Age- and cell-related gene expression of aromatase and estrogen receptors in the rat testis. J Mol Endocrinol 45: 147-59.
Braun JM, Just AC, Williams PL, Smith KW, Calafat AM, Hauser R. 2014. Personal care product use and urinary phthalate metabolite and paraben concentrations during pregnancy among women from a fertility clinic. J Expo Sci Environ Epidemiol 24: 459-66.
Bulun SE, Takayama K, Suzuki T, Sasano H, Yilmaz B, Sebastian S. 2004. Organization of the human aromatase p450 (CYP19) gene. Semin Reprod Med 22: 5-9.
Carreau S, Bois C, Zanatta L, Silva FR, Bouraima-Lelong H, Delalande C. 2011a. Estrogen signaling in testicular cells. Life Sci 89: 584-7.
Carreau S, Bouraima-Lelong H, Delalande C. 2011b. Estrogens: new players in spermatogenesis. Reprod Biol 11: 174-93.
Carreau S, Bourguiba S, Lambard S, Galeraud-Denis I, Genissel C, Bilinska B, et al. 2001. Aromatase expression in male germ cells. J Steroid Biochem Mol Biol 79: 203-8.
Carreau S, de Vienne C, Galeraud-Denis I. 2008. Aromatase and estrogens in man reproduction: a review and latest advances. Adv Med Sci 53: 139-44.
Carreau S, Delalande C, Galeraud-Denis I. 2009. Mammalian sperm quality and aromatase expression. Microsc Res Tech 72: 552-7.
Carreau S, Delalande C, Silandre D, Bourguiba S, Lambard S. 2006. Aromatase and estrogen receptors in male reproduction. Mol Cell Endocrinol 246: 65-8.
Carreau S, Genissel C, Bilinska B, Levallet J. 1999. Sources of oestrogen in the testis and reproductive tract of the male. Int J Androl 22: 211-23.
Carreau S, Isabelle GD. 2007. Transcripts of aromatase and estrogen receptors and significance of other RNAs in human spermatozoa. Arch Androl 53: 249-55.
Carreau S, Lambard S, Delalande C, Denis-Galeraud I, Bilinska B, Bourguiba S. 2003. Aromatase expression and role of estrogens in male gonad : a review. Reprod Biol Endocrinol 1: 35.
Carreau S, Silandre D, Bourguiba S, Hamden K, Said L, Lambard S, et al. 2007. Estrogens and male reproduction: a new concept. Braz J Med Biol Res 40: 761-8.
Carreau S, Wolczynski S, Galeraud-Denis I. 2010. Aromatase, oestrogens and human male reproduction. Philos Trans R Soc Lond B Biol Sci 365: 1571-9.
Chawla AS, Hinberg I. 1991. Leaching of plasticizers from and surface characterization of PVC blood platelet bags. Biomater Artif Cells Immobilization Biotechnol 19: 761-83.
Clark KE, David RM, Guinn R, Kramarz KW, Lampi MA, Staples CA. 2011. Modeling Human Exposure to Phthalate Esters: A Comparison of Indirect and Biomonitoring Estimation Methods. Hum Ecol Risk Assess 17: 923-65.
Conley A, Hinshelwood M. 2001. Mammalian aromatases. Reproduction 121: 685-95.
David RM. 2006. Proposed mode of action for in utero effects of some phthalate esters on the developing male reproductive tract. Toxicol Pathol 34: 209-19.
Delmaar C, Bokkers B, Ter Burg W, Schuur G. 2014. Validation of an aggregate exposure model for substances in consumer products: a case study of diethyl phthalate in personal care products. J Expo Sci Environ Epidemiol.
Desdoits-Lethimonier C, Albert O, Le Bizec B, Perdu E, Zalko D, Courant F, et al. 2012. Human testis steroidogenesis is inhibited by phthalates. Hum Reprod 27: 1451-9.
Duty SM, Ackerman RM, Calafat AM, Hauser R. 2005a. Personal care product use predicts urinary concentrations of some phthalate monoesters. Environ Health Perspect 113: 1530-5.
Duty SM, Calafat AM, Silva MJ, Ryan L, Hauser R. 2005b. Phthalate exposure and reproductive hormones in adult men. Hum Reprod 20: 604-10.
Duty SM, Silva MJ, Barr DB, Brock JW, Ryan L, Chen Z, et al. 2003. Phthalate exposure and human semen parameters. Epidemiology 14: 269-77.
Erdos Z, Pearson K, Goedken M, Menzel K, Sistare FD, Glaab WE, et al. 2013. Inhibin B response to testicular toxicants hexachlorophene, ethane dimethane sulfonate, di-(n-butyl)-phthalate, nitrofurazone, DL-ethionine, 17-alpha ethinylestradiol, 2,5-hexanedione, or carbendazim following short-term dosing in male rats. Birth Defects Res B Dev Reprod Toxicol 98: 41-53.
Esteves SC, Zini A, Aziz N, Alvarez JG, Sabanegh ES, Jr., Agarwal A. 2012. Critical appraisal of World Health Organization's new reference values for human semen characteristics and effect on diagnosis and treatment of subfertile men. Urology 79: 16-22.
Fisher CR, Graves KH, Parlow AF, Simpson ER. 1998. Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene. Proc Natl Acad Sci U S A 95: 6965-70.
Foster PM. 2005. Mode of action: impaired fetal leydig cell function--effects on male reproductive development produced by certain phthalate esters. Crit Rev Toxicol 35: 713-9.
Foster PM. 2006. Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. Int J Androl 29: 140-7; discussion 81-5.
Ge RS, Chen GR, Tanrikut C, Hardy MP. 2007. Phthalate ester toxicity in Leydig cells: developmental timing and dosage considerations. Reprod Toxicol 23: 366-73.
Gray LE, Jr., Wilson VS, Stoker T, Lambright C, Furr J, Noriega N, et al. 2006. Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals. Int J Androl 29: 96-104; discussion 5-8.
Guengerich FP, Johnson WW. 1997. Kinetics of ferric cytochrome P450 reduction by NADPH-cytochrome P450 reductase: rapid reduction in the absence of substrate and variations among cytochrome P450 systems. Biochemistry 36: 14741-50.
Guo Y, Kannan K. 2013. A survey of phthalates and parabens in personal care products from the United States and its implications for human exposure. Environ Sci Technol 47: 14442-9.
Han X, Cui Z, Zhou N, Ma M, Li L, Li Y, et al. 2013. Urinary phthalate metabolites and male reproductive function parameters in Chongqing general population, China. Int J Hyg Environ Health.
Han X, Cui Z, Zhou N, Ma M, Li L, Li Y, et al. 2014. Urinary phthalate metabolites and male reproductive function parameters in Chongqing general population, China. Int J Hyg Environ Health 217: 271-8.
Harris CA, Henttu P, Parker MG, Sumpter JP. 1997. The estrogenic activity of phthalate esters in vitro. Environ Health Perspect 105: 802-11.
Hauser R, Calafat AM. 2005a. Phthalates and human health. Occup Environ Med 62: 806-18.
Hauser R, Calafat AM. 2005b. Phthalates and human health. Occupational and Environmental Medicine 62.
Hauser R, Duty S, Godfrey-Bailey L, Calafat AM. 2004. Medications as a source of human exposure to phthalates. Environ Health Perspect 112: 751-3.
Hauser R, Meeker JD, Duty S, Silva MJ, Calafat AM. 2006. Altered semen quality in relation to urinary concentrations of phthalate monoester and oxidative metabolites. Epidemiology 17: 682-91.
Hauser R, Meeker JD, Singh NP, Silva MJ, Ryan L, Duty S, et al. 2007. DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Hum Reprod 22: 688-95.
Hernandez-Diaz S, Mitchell AA, Kelley KE, Calafat AM, Hauser R. 2009. Medications as a potential source of exposure to phthalates in the U.S. population. Environ Health Perspect 117: 185-9.
Herr C, zur Nieden A, Koch HM, Schuppe HC, Fieber C, Angerer J, et al. 2009. Urinary di(2-ethylhexyl)phthalate (DEHP)--metabolites and male human markers of reproductive function. Int J Hyg Environ Health 212: 648-53.
Hess RA, Bunick D, Bahr J. 2001. Oestrogen, its receptors and function in the male reproductive tract - a review. Mol Cell Endocrinol 178: 29-38.
Hess RA, Bunick D, Lee KH, Bahr J, Taylor JA, Korach KS, et al. 1997. A role for oestrogens in the male reproductive system. Nature 390: 509-12.
Horng SG, Wang TH, Wang HS. 2008. Estradiol-to-testosterone ratio is associated with response to metformin treatment in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Chang Gung Med J 31: 477-83.
Hu Y, Wang R, Xiang Z, Qian W, Han X, Li D. 2014. Antagonistic effects of a mixture of low-dose nonylphenol and di-n-butyl phthalate (monobutyl phthalate) on the Sertoli cells and serum reproductive hormones in prepubertal male rats in vitro and in vivo. PLoS One 9: e93425.
Hubinger JC, Havery DC. 2006. Analysis of consumer cosmetic products for phthalate esters. J Cosmet Sci 57: 127-37.
Inkster S, Yue W, Brodie A. 1995. Human testicular aromatase: immunocytochemical and biochemical studies. J Clin Endocrinol Metab 80: 1941-7.
Itoh H, Yoshida K, Masunaga S. 2005. Evaluation of the effect of governmental control of human exposure to two phthalates in Japan using a urinary biomarker approach. Int J Hyg Environ Health 208: 237-45.
Janulis L, Bahr JM, Hess RA, Janssen S, Osawa Y, Bunick D. 1998. Rat testicular germ cells and epididymal sperm contain active P450 aromatase. J Androl 19: 65-71.
Janulis L, Hess RA, Bunick D, Nitta H, Janssen S, Asawa Y, et al. 1996. Mouse epididymal sperm contain active P450 aromatase which decreases as sperm traverse the epididymis. J Androl 17: 111-6.
Jobling S, Reynolds T, White R, Parker MG, Sumpter JP. 1995. A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. Environ Health Perspect 103: 582-7.
Joensen UN, Frederiksen H, Jensen MB, Lauritsen MP, Olesen IA, Lassen TH, et al. 2012. Phthalate excretion pattern and testicular function: a study of 881 healthy Danish men. Environ Health Perspect 120: 1397-403.
Johnson KJ, Heger NE, Boekelheide K. 2012. Of mice and men (and rats): phthalate-induced fetal testis endocrine disruption is species-dependent. Toxicol Sci 129: 235-48.
Johnson KJ, McDowell EN, Viereck MP, Xia JQ. 2011. Species-specific dibutyl phthalate fetal testis endocrine disruption correlates with inhibition of SREBP2-dependent gene expression pathways. Toxicol Sci 120: 460-74.
Jonsson BA, Richthoff J, Rylander L, Giwercman A, Hagmar L. 2005. Urinary phthalate metabolites and biomarkers of reproductive function in young men. Epidemiology 16: 487-93.
Jurewicz J, Radwan M, Sobala W, Ligocka D, Radwan P, Bochenek M, et al. 2013. Human urinary phthalate metabolites level and main semen parameters, sperm chromatin structure, sperm aneuploidy and reproductive hormones. Reprod Toxicol 42: 232-41.
Kawasaki T, Uezono K, Itoh K, Ueno M. 1991. [Prediction of 24-hour urinary creatinine excretion from age, body weight and height of an individual and its application]. Nihon Koshu Eisei Zasshi 38: 567-74.
Kim HS, Saito K, Ishizuka M, Kazusaka A, Fujita S. 2003. Short period exposure to di-(2-ethylhexyl) phthalate regulates testosterone metabolism in testis of prepubertal rats. Arch Toxicol 77: 446-51.
Koch HM, Bolt HM, Preuss R, Angerer J. 2005. New metabolites of di(2-ethylhexyl)phthalate (DEHP) in human urine and serum after single oral doses of deuterium-labelled DEHP. Arch Toxicol 79: 367-76.
Koch HM, Drexler H, Angerer J. 2003. An estimation of the daily intake of di(2-ethylhexyl)phthalate (DEHP) and other phthalates in the general population. Int J Hyg Environ Health 206: 77-83.
Koniecki D, Wang R, Moody RP, Zhu J. 2011. Phthalates in cosmetic and personal care products: concentrations and possible dermal exposure. Environ Res 111: 329-36.
Kurahashi N, Kondo T, Omura M, Umemura T, Ma M, Kishi R. 2005. The effects of subacute inhalation of di (2-ethylhexyl) phthalate (DEHP) on the testes of prepubertal Wistar rats. J Occup Health 47: 437-44.
Lambard S, Galeraud-Denis I, Saunders PT, Carreau S. 2004. Human immature germ cells and ejaculated spermatozoa contain aromatase and oestrogen receptors. J Mol Endocrinol 32: 279-89.
Lazaros L, Xita N, Kaponis A, Hatzi E, Plachouras N, Sofikitis N, et al. 2011. The association of aromatase (CYP19) gene variants with sperm concentration and motility. Asian J Androl 13: 292-7.
Lazaros L, Xita N, Takenaka A, Sofikitis N, Makrydimas G, Stefos T, et al. 2012. Semen quality is influenced by androgen receptor and aromatase gene synergism. Hum Reprod 27: 3385-92.
Lee YJ, Lee E, Kim TH, Choi JS, Lee J, Jung KK, et al. 2009. Effects of Di(2-ethylhexyl) Phthalate on Regulation of Steroidogenesis or Spermatogenesis in Testes of Sprague-Dawley Rats. Journal of Health Science 55: 380-8.
Leitz J, Kuballa T, Rehm J, Lachenmeier DW. 2009. Chemical analysis and risk assessment of diethyl phthalate in alcoholic beverages with special regard to unrecorded alcohol. PLoS One 4: e8127.
Levallet J, Bilinska B, Mittre H, Genissel C, Fresnel J, Carreau S. 1998. Expression and immunolocalization of functional cytochrome P450 aromatase in mature rat testicular cells. Biol Reprod 58: 919-26.
Li G, Sun DX, Yu Y, Liu WJ, Tang SQ, Zhang Y, et al. 2011. Genetic effect of the follicle-stimulating hormone receptor gene on reproductive traits in Beijing You chickens. Poult Sci 90: 2487-92.
Li XW, Liang Y, Su Y, Deng H, Li XH, Guo J, et al. 2012. Adverse effects of di-(2-ethylhexyl) phthalate on Leydig cell regeneration in the adult rat testis. Toxicol Lett 215: 84-91.
Liu L, Bao H, Liu F, Zhang J, Shen H. 2012. Phthalates exposure of Chinese reproductive age couples and its effect on male semen quality, a primary study. Environ Int 42: 78-83.
Meeker JD, Calafat AM, Hauser R. 2009a. Urinary metabolites of di(2-ethylhexyl) phthalate are associated with decreased steroid hormone levels in adult men. J Androl 30: 287-97.
Meeker JD, Sathyanarayana S, Swan SH. 2009b. Phthalates and other additives in plastics: human exposure and associated health outcomes. Philos Trans R Soc Lond B Biol Sci 364: 2097-113.
Mendiola J, Jorgensen N, Andersson AM, Calafat AM, Silva MJ, Redmon JB, et al. 2011. Associations between urinary metabolites of di(2-ethylhexyl) phthalate and reproductive hormones in fertile men. Int J Androl 34: 369-78.
Mendiola J, Meeker JD, Jorgensen N, Andersson AM, Liu F, Calafat AM, et al. 2012. Urinary concentrations of di(2-ethylhexyl) phthalate metabolites and serum reproductive hormones: pooled analysis of fertile and infertile men. J Androl 33: 488-98.
Moody S, Goh H, Bielanowicz A, Rippon P, Loveland KL, Itman C. 2013. Prepubertal Mouse Testis Growth and Maturation and Androgen Production Are Acutely Sensitive to Di-n-butyl Phthalate. Endocrinology 154: 3460-75.
Moss JL, Crosnoe LE, Kim ED. 2013. Effect of rejuvenation hormones on spermatogenesis. Fertil Steril 99: 1814-20.
Mylchreest E, Sar M, Wallace DG, Foster PM. 2002. Fetal testosterone insufficiency and abnormal proliferation of Leydig cells and gonocytes in rats exposed to di(n-butyl) phthalate. Reprod Toxicol 16: 19-28.
Nakai M, Tabira Y, Asai D, Yakabe Y, Shimyozu T, Noguchi M, et al. 1999. Binding characteristics of dialkyl phthalates for the estrogen receptor. Biochem Biophys Res Commun 254: 311-4.
Nitta H, Bunick D, Hess RA, Janulis L, Newton SC, Millette CF, et al. 1993. Germ cells of the mouse testis express P450 aromatase. Endocrinology 132: 1396-401.
Noda M, Ohno S, Nakajin S. 2007. Mono-(2-ethylhexyl) phthalate (MEHP) induces nuclear receptor 4A subfamily in NCI-H295R cells: a possible mechanism of aromatase suppression by MEHP. Mol Cell Endocrinol 274: 8-18.
Oliva A, Spira A, Multigner L. 2001. Contribution of environmental factors to the risk of male infertility. Hum Reprod 16: 1768-76.
Pan G, Hanaoka T, Yoshimura M, Zhang S, Wang P, Tsukino H, et al. 2006. Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China. Environ Health Perspect 114: 1643-8.
Pant N, Shukla M, Kumar Patel D, Shukla Y, Mathur N, Kumar Gupta Y, et al. 2008. Correlation of phthalate exposures with semen quality. Toxicol Appl Pharmacol 231: 112-6.
Papadopoulos V, Drosdowsky MA, Carreau S. 1986. In vitro effects of prolactin and dexamethasone on rat Leydig cell aromatase activity. Andrologia 18: 79-83.
Parks LG, Ostby JS, Lambright CR, Abbott BD, Klinefelter GR, Barlow NJ, et al. 2000. The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol Sci 58: 339-49.
Parlett LE, Calafat AM, Swan SH. 2013a. Women's exposure to phthalates in relation to use of personal care products. Journal of Exposure Science and Environmental Epidemiology 23: 197-206.
Parlett LE, Calafat AM, Swan SH. 2013b. Women's exposure to phthalates in relation to use of personal care products. J Expo Sci Environ Epidemiol 23: 197-206.
Phillips KP, Tanphaichitr N. 2008. Human exposure to endocrine disrupters and semen quality. J Toxicol Environ Health B Crit Rev 11: 188-220.
Poongothai J, Gopenath TS, Manonayaki S. 2009. Genetics of human male infertility. Singapore Med J 50: 336-47.
Queiroz EK, Waissmann W. 2006. Occupational exposure and effects on the male reproductive system. Cad Saude Publica 22: 485-93.
Robertson KM, O'Donnell L, Jones ME, Meachem SJ, Boon WC, Fisher CR, et al. 1999. Impairment of spermatogenesis in mice lacking a functional aromatase (cyp 19) gene. Proc Natl Acad Sci U S A 96: 7986-91.
Robertson KM, Simpson ER, Lacham-Kaplan O, Jones ME. 2001. Characterization of the fertility of male aromatase knockout mice. J Androl 22: 825-30.
Romero-Franco M, Hernandez-Ramirez RU, Calafat AM, Cebrian ME, Needham LL, Teitelbaum S, et al. 2011a. Personal care product use and urinary levels of phthalate metabolites in Mexican women. Environment International 37: 867-71.
Romero-Franco M, Hernandez-Ramirez RU, Calafat AM, Cebrian ME, Needham LL, Teitelbaum S, et al. 2011b. Personal care product use and urinary levels of phthalate metabolites in Mexican women. Environ Int 37: 867-71.
Rommerts FF, de Jong FH, Brinkmann AO, van der Molen HJ. 1982. Development and cellular localization of rat testicular aromatase activity. J Reprod Fertil 65: 281-8.
Rudel RA, Camann DE, Spengler JD, Korn LR, Brody JG. 2003. Phthalates, alkylphenols, pesticides, polybrominated diphenyl ethers, and other endocrine-disrupting compounds in indoor air and dust. Environ Sci Technol 37: 4543-53.
Ryu JY, Lee BM, Kacew S, Kim HS. 2007. Identification of differentially expressed genes in the testis of Sprague-Dawley rats treated with di(n-butyl) phthalate. Toxicology 234: 103-12.
Ryu JY, Lee E, Kim TH, Lee YJ, Lee J, Lee BM, et al. 2008. Time-response effects of testicular gene expression profiles in Sprague-Dawley male rats treated with di(n-butyl) phthalate. J Toxicol Environ Health A 71: 1542-9.
Samandar E, Silva MJ, Reidy JA, Needham LL, Calafat AM. 2009. Temporal stability of eight phthalate metabolites and their glucuronide conjugates in human urine. Environ Res 109: 641-6.
Sampson J, de Korte D. 2011. DEHP-plasticised PVC: relevance to blood services. Transfus Med 21: 73-83.
Savchuk SA, Nuzhnyi VP, Kolesov GM. 2006. Factors affecting the accuracy of the determination of diethyl phthalate in vodka, ethanol, and samples of illegal alcoholic products. Journal of Analytical Chemistry 61: 1198-203.
Saylam B, Efesoy O, Cayan S. 2011. The effect of aromatase inhibitor letrozole on body mass index, serum hormones, and sperm parameters in infertile men. Fertil Steril 95: 809-11.
Schlegel PN. 2012. Aromatase inhibitors for male infertility. Fertil Steril 98: 1359-62.
Sharpe RM, Skakkebaek NE. 2008. Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects. Fertil Steril 89: e33-8.
Shultz VD, Phillips S, Sar M, Foster PM, Gaido KW. 2001. Altered gene profiles in fetal rat testes after in utero exposure to di(n-butyl) phthalate. Toxicol Sci 64: 233-42.
Silandre D, Delalande C, Durand P, Carreau S. 2007. Three promoters PII, PI.f, and PI.tr direct the expression of aromatase (cyp19) gene in male rat germ cells. J Mol Endocrinol 39: 169-81.
Silva FR, Leite LD, Wassermann GF. 2002. Rapid signal transduction in Sertoli cells. Eur J Endocrinol 147: 425-33.
Silva MJ, Slakman AR, Reidy JA, Preau JL, Jr., Herbert AR, Samandar E, et al. 2004. Analysis of human urine for fifteen phthalate metabolites using automated solid-phase extraction. J Chromatogr B Analyt Technol Biomed Life Sci 805: 161-7.
Simpson ER, Clyne C, Rubin G, Boon WC, Robertson K, Britt K, et al. 2002. Aromatase--a brief overview. Annu Rev Physiol 64: 93-127.
Simpson WL, Jr., Rausch DR. 2009. Imaging of male infertility: pictorial review. AJR Am J Roentgenol 192: S98-107 (Quiz S8-11).
Sioen I, Fierens T, Van Holderbeke M, Geerts L, Bellemans M, De Maeyer M, et al. 2012. Phthalates dietary exposure and food sources for Belgian preschool children and adults. Environ Int 48: 102-8.
Specht IO, Toft G, Hougaard KS, Lindh CH, Lenters V, Jonsson BAG, et al. 2014. Associations between serum phthalates and biomarkers of reproductive function in 589 adult men. Environment International 66: 146-56.
Stahl PJ, Stember DS, Goldstein M. 2012. Contemporary management of male infertility. Annu Rev Med 63: 525-40.
Takeuchi S, Iida M, Kobayashi S, Jin K, Matsuda T, Kojima H. 2005. Differential effects of phthalate esters on transcriptional activities via human estrogen receptors alpha and beta, and androgen receptor. Toxicology 210: 223-33.
Van Holderbeke M, Geerts L, Vanermen G, Servaes K, Sioen I, De Henauw S, et al. 2014. Determination of contamination pathways of phthalates in food products sold on the Belgian market. Environ Res 134C: 345-52.
Walker WH, Cheng J. 2005. FSH and testosterone signaling in Sertoli cells. Reproduction 130: 15-28.
Wang X, Yang Y, Zhang L, Ma Y, Han J, Yang L, et al. 2013. Endocrine disruption by di-(2-ethylhexyl)-phthalate in Chinese rare minnow (Gobiocypris rarus). Environ Toxicol Chem 32: 1846-54.
Wirth JJ, Rossano MG, Potter R, Puscheck E, Daly DC, Paneth N, et al. 2008. A pilot study associating urinary concentrations of phthalate metabolites and semen quality. Syst Biol Reprod Med 54: 143-54.
Wittassek M, Heger W, Koch HM, Becker K, Angerer J, Kolossa-Gehring M. 2007. Daily intake of di(2-ethylhexyl)phthalate (DEHP) by German children -- A comparison of two estimation models based on urinary DEHP metabolite levels. Int J Hyg Environ Health 210: 35-42.
Wittassek M, Koch HM, Angerer J, Bruning T. 2011. Assessing exposure to phthalates - the human biomonitoring approach. Mol Nutr Food Res 55: 7-31.
Wu CF, Chang-Chien GP, Su SW, Chen BH, Wu MT. 2014. Findings of 2731 suspected phthalate-tainted foodstuffs during the 2011 phthalates incident in Taiwan. J Formos Med Assoc 113: 600-5.
Ye T, Kang M, Huang Q, Fang C, Chen Y, Shen H, et al. 2014. Exposure to DEHP and MEHP from hatching to adulthood causes reproductive dysfunction and endocrine disruption in marine medaka (Oryzias melastigma). Aquat Toxicol 146: 115-26.
Zavos A, Daponte A, Garas A, Verykouki C, Papanikolaou E, Anifandis G, et al. 2013. Double versus single homologous intrauterine insemination for male factor infertility: a systematic review and meta-analysis. Asian J Androl 15: 533-8.
Zhang XF, Zhang T, Wang L, Zhang HY, Chen YD, Qin XS, et al. 2013. Effects of diethylhexyl phthalate (DEHP) given neonatally on spermatogenesis of mice. Mol Biol Rep 40: 6509-17.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊
 
系統版面圖檔 系統版面圖檔