不孕與正常懷孕婦女體內金屬濃度與相關影響因子之探討

• Main Author: 廖凱威
• Other Authors: 公共衛生學研究所
• Language: Chinese; English
• Published: 2010
• Subjects: Arctic; Canada; Dent; Milton; Wilcox; McMahon; Munk; O'Connor; Fontana; Henson; Rowland; Berglund; Clarkson; Renna; Seddon; Gardiner; renna
• Online Access: http://libir.tmu.edu.tw/handle/987654321/36303

目錄 第一章 緒論 5 第一節 研究背景與動機 5 第二節 研究目的 6 第三節 研究架構與假說 7 第二章 文獻探討 8 第一節 女性生殖生理學 8 第二節 影響婦女不孕之相關因子 10 第三節 人體金屬暴露途徑 11 第四節 影響婦女不孕之體內金屬與相關研究 12 第五節 影響婦女體內金屬濃度的因子 16 第六節 重金屬對女性體內荷爾蒙的影響 17 第七節 生物指標之選擇 18 第三章 材料與方法 19 第一節 研究設計與流程 19 第二節 資料及樣本收集 21 第三節 實驗器材 22 第四節 實驗方法 23 第五節 資料分析方法 28 第四章 結果與討論 29 第一節 研究對象基本人口學特性 29 第二節 不孕與懷孕婦女體內金屬濃度分析結果 35 第三節 婦女體內金屬濃度高低族群與相關因子分析比較 41 第四節 影響婦女血液金屬濃度之複迴歸模式建立 45 第五節 婦女髮汞濃度高低族群與相關因子之分析比較 49 第六節 婦女發生不孕之邏輯斯迴歸分析 51 第七節 不孕組與懷孕組食用魚類與認知情形 53 第五章 結論與建議 59 第一節 研究限制 61 第二節 結論 59 第三節 建議 61 參考文獻 62 表目錄 表3-1 血液標準品之精密度與準確度分析結果 26 表3-2 血液-標準添加之回收率分析結果-鉛 27 表3-3 血液-標準添加之回收率分析結果-鎘 27 表3-4 血液-標準添加之回收率分析結果-砷 27 表3-5 血液-標準添加之回收率分析結果-汞 27 表3-6 頭髮標準品之精密度與準確度分析結果 27 表3-7 頭髮-標準添加之回收率分析結果-汞 27 表4-1 不孕組與懷孕組基本人口學特徵 30 表4-2 不孕組與懷孕組的生活型態與飲食習慣 32 表4-3 不孕組生理與生殖荷爾蒙特徵 34 表4-4 不孕組體內生殖荷爾蒙濃度分佈情形 34 表4-5 婦女金屬濃度分佈情形 37 表4-6 不孕組血液中金屬濃度與荷爾蒙之間的相關性 38 表4-7 懷孕組血液中金屬濃度之間的相關性 38 表4-8不孕組基本人口學特徵、生活習慣、飲食習慣與體內金屬濃度之相關(n=384) 40 表4-9 懷孕組基本人口學特徵、生活習慣、飲食習慣與體內金屬濃度之相關(n=58) 40 表4-10 不孕組血汞濃度高低族群之相關因子比較分析(n=381) 41 表4-11 不孕組血鉛濃度高低族群之相關因子比較分析(n=384) 42 表4-12 不孕組血鎘濃度高低族群之相關因子比較分析(n=384) 43 表4-13 不孕組血砷濃度高低族群之相關因子比較分析(n=384) 44 表4-14 不孕組LOG血中金屬濃度之複迴歸模式分析 46 表4-15 懷孕組LOG血中金屬濃度之複迴歸模式分析 48 表4-16 不孕組髮中汞濃度高低族群之相關因子比較分析(n=217) 49 表4-17 懷孕組髮汞濃度高低族群之相關因子比較分析(n=29) 50 表4-18 婦女發生不孕之邏輯斯複迴歸分析 52 圖目錄 圖1-1 研究架構圖 7 圖2-1性腺軸 8 圖2-2金屬進入人體方式及其代謝途徑 11 圖3-1 不孕婦女研究流程圖 19 圖3-2 懷孕婦女研究流程圖 20 圖3-3 髮中汞檢量線圖 24 圖3-4 血中汞檢量線圖 24 圖3-5 鉛檢量線圖 25 圖3-6 鎘檢量線圖 25 圖3-7 砷檢量線圖 25 圖4-1 不孕婦女與懷孕婦女血中汞濃度分佈圖 36 圖4-2 不孕婦女與懷孕婦女髮中汞濃度分佈圖 36 圖4-3 不孕組與懷孕組最常食用的魚類百分比 53 圖4-4 不孕組與懷孕組最常食用的生魚片種類百分比 54 圖4-5 不孕組將來懷孕魚類攝取增加的原因 55 圖4-6不孕組將來懷孕魚類攝取減少的原因 55 圖4-7 懷孕組懷孕時魚類攝取增加的原因 56 圖4-8 懷孕組懷孕時魚類攝取減少的原因 56 圖4-9 不孕組與懷孕組對U.S EPA/FDA公布四種高汞魚類的認知 57 圖4-10 當知道訊息後是否會改變吃魚的量 58 Ahmad, S. A., Sayed, M. H., Barua, S., Khan, M. H., Faruquee, M. H., Jalil, A., et al. (2001). Arsenic in drinking water and pregnancy outcomes. Environ Health Perspect, 109(6), 629-631. Al-Saleh, I., Coskun, S., Mashhour, A., Shinwari, N., El-Doush, I., Billedo, G., et al. (2008). Exposure to heavy metals (lead, cadmium and mercury) and its effect on the outcome of in-vitro fertilization treatment. Int J Hyg Environ Health, 211(5-6), 560-579. Amin-zaki, L., Majeed, M. A., Clarkson, T. W., & Greenwood, M. R. (1978). Methylmercury poisoning in Iraqi children: clinical observations over two years. Br Med J, 1(6113), 613-616. Ask, K., Akesson, A., Berglund, M., & Vahter, M. (2002). Inorganic mercury and methylmercury in placentas of Swedish women. Environ Health Perspect, 110(5), 523-526. Baird, D. D., Umbach, D. M., Lansdell, L., Hughes, C. L., Setchell, K. D., Weinberg, C. R., et al. (1995). Dietary intervention study to assess estrogenicity of dietary soy among postmenopausal women. J Clin Endocrinol Metab, 80(5), 1685-1690. Bellinger, D. C. (2005). Teratogen update: lead and pregnancy. Birth Defects Res A Clin Mol Teratol, 73(6), 409-420. Buettner, C., Mukamal, K. J., Gardiner, P., Davis, R. B., Phillips, R. S., & Mittleman, M. A. (2009). Herbal supplement use and blood lead levels of United States adults. J Gen Intern Med, 24(11), 1175-1182. Butler Walker, J., Houseman, J., Seddon, L., McMullen, E., Tofflemire, K., Mills, C., et al. (2006). Maternal and umbilical cord blood levels of mercury, lead, cadmium, and essential trace elements in Arctic Canada. Environ Res, 100(3), 295-318. Cagiano, R., De Salvia, M. A., Renna, G., Tortella, E., Braghiroli, D., Parenti, C., et al. (1990). Evidence that exposure to methyl mercury during gestation induces behavioral and neurochemical changes in offspring of rats. Neurotoxicol Teratol, 12(1), 23-28. CDC. (1991). Preventing Lead Poisoning in Young Children, a Statement by the Centers for Disease Control. Public Health Service. Chang, S. H., Cheng, B. H., Lee, S. L., Chuang, H. Y., Yang, C. Y., Sung, F. C., et al. (2006). Low blood lead concentration in association with infertility in women. Environ Res, 101(3), 380-386. Choy, C. M., Lam, C. W., Cheung, L. T., Briton-Jones, C. M., Cheung, L. P., & Haines, C. J. (2002). Infertility, blood mercury concentrations and dietary seafood consumption: a case-control study. Bjog, 109(10), 1121-1125. Colquitt, P. J. (1995). The effect of occupational exposure to mercury vapour on the fertility of female dental assistants. Occup Environ Med, 52(3), 214. Concha, G., Vogler, G., Nermell, B., & Vahter, M. (2002). Intra-individual variation in the metabolism of inorganic arsenic. Int Arch Occup Environ Health, 75(8), 576-580. Davis, B. J., Price, H. C., O'Connor, R. W., Fernando, R., Rowland, A. S., & Morgan, D. L. (2001). Mercury vapor and female reproductive toxicity. Toxicol Sci, 59(2), 291-296. Diez, S., Montuori, P., Pagano, A., Sarnacchiaro, P., Bayona, J. M., & Triassi, M. (2008). Hair mercury levels in an urban population from southern Italy: fish consumption as a determinant of exposure. Environ Int, 34(2), 162-167. Ford, J. H., MacCormac, L., & Hiller, J. (1994). PALS (pregnancy and lifestyle study): association between occupational and environmental exposure to chemicals and reproductive outcome. Mutat Res, 313(2-3), 153-164. Foster, W. G., McMahon, A., & Rice, D. C. (1996). Subclinical changes in luteal function in cynomolgus monkeys with moderate blood lead levels. J Appl Toxicol, 16(2), 159-163. Franks, P. A., Laughlin, N. K., Dierschke, D. J., Bowman, R. E., & Meller, P. A. (1989). Effects of lead on luteal function in rhesus monkeys. Biol Reprod, 41(6), 1055-1062. Gasana, J., Hlaing, W. M., Siegel, K. A., Chamorro, A., & Niyonsenga, T. (2006). Blood lead levels in children and environmental lead contamination in Miami inner city, Florida. Int J Environ Res Public Health, 3(3), 228-234. Gavard, J. A., & Artal, R. (2008). Effect of exercise on pregnancy outcome. Clin Obstet Gynecol, 51(2), 467-480. Gerhard, I., Monga, B., Waldbrenner, A., & Runnebaum, B. (1998). Heavy metals and fertility. J Toxicol Environ Health A, 54(8), 593-611. Gilbert, S. G., & Weiss, B. (2006). A rationale for lowering the blood lead action level from 10 to 2 microg/dL. Neurotoxicology, 27(5), 693-701. Heilier, J. F., Verougstraete, V., Nackers, F., Tonglet, R., Donnez, J., & Lison, D. (2004). Assessment of cadmium impregnation in women suffering from endometriosis: a preliminary study. Toxicol Lett, 154(1-2), 89-93. Henson, M. C., & Chedrese, P. J. (2004). Endocrine disruption by cadmium, a common environmental toxicant with paradoxical effects on reproduction. Exp Biol Med (Maywood), 229(5), 383-392. Iavicoli, I., Fontana, L., & Bergamaschi, A. (2009). The effects of metals as endocrine disruptors. J Toxicol Environ Health B Crit Rev, 12(3), 206-223. Inhorn, M. C., King, L., Nriagu, J. O., Kobeissi, L., Hammoud, N., Awwad, J., et al. (2008). Occupational and environmental exposures to heavy metals: risk factors for male infertility in Lebanon? Reprod Toxicol, 25(2), 203-212. Joffe, M., & Li, Z. (1994). Male and female factors in fertility. Am J Epidemiol, 140(10), 921-929. Kim, E. H., Kim, I. K., Kwon, J. Y., Kim, S. W., & Park, Y. W. (2006). The effect of fish consumption on blood mercury levels of pregnant women. Yonsei Med J, 47(5), 626-633. Lee, M. G., Chun, O. K., & Song, W. O. (2005). Determinants of the blood lead level of US women of reproductive age. J Am Coll Nutr, 24(1), 1-9. Mahaffey, K. R., Clickner, R. P., & Jeffries, R. A. (2009). Adult women's blood mercury concentrations vary regionally in the United States: association with patterns of fish consumption (NHANES 1999-2004). Environ Health Perspect, 117(1), 47-53. Martin, M. B., Reiter, R., Pham, T., Avellanet, Y. R., Camara, J., Lahm, M., et al. (2003). Estrogen-like activity of metals in MCF-7 breast cancer cells. Endocrinology, 144(6), 2425-2436. McGivern, R. F., Sokol, R. Z., & Berman, N. G. (1991). Prenatal lead exposure in the rat during the third week of gestation: long-term behavioral, physiological, and anatomical effects associated with reproduction. Toxicol Appl Pharmacol, 110(2), 206-215. Menken, J., Trussell, J., & Larsen, U. (1986). Age and infertility. Science, 233(4771), 1389-1394. Milton, A. H., Smith, W., Rahman, B., Hasan, Z., Kulsum, U., Dear, K., et al. (2005). Chronic arsenic exposure and adverse pregnancy outcomes in bangladesh. Epidemiology, 16(1), 82-86. Ohno, T., Sakamoto, M., Kurosawa, T., Dakeishi, M., Iwata, T., & Murata, K. (2007). Total mercury levels in hair, toenail, and urine among women free from occupational exposure and their relations to renal tubular function. Environ Res, 103(2), 191-197. Pillai, A., Laxmi Priya, P. N., & Gupta, S. (2002). Effects of combined exposure to lead and cadmium on pituitary membrane of female rats. Arch Toxicol, 76(12), 671-675. Pinon-Lataillade, G., Thoreux-Manlay, A., Coffigny, H., Masse, R., & Soufir, J. C. (1995). Reproductive toxicity of chronic lead exposure in male and female mice. Hum Exp Toxicol, 14(11), 872-878. Rahman, A., Vahter, M., Ekstrom, E. C., Rahman, M., Golam Mustafa, A. H., Wahed, M. A., et al. (2007). Association of arsenic exposure during pregnancy with fetal loss and infant death: a cohort study in Bangladesh. Am J Epidemiol, 165(12), 1389-1396. Rowland, A. S., Baird, D. D., Weinberg, C. R., Shore, D. L., Shy, C. M., & Wilcox, A. J. (1994). The effect of occupational exposure to mercury vapour on the fertility of female dental assistants. Occup Environ Med, 51(1), 28-34. Safe, S. (2003). Cadmium's disguise dupes the estrogen receptor. Nat Med, 9(8), 1000-1001. Sakamoto, M., Kubota, M., Murata, K., Nakai, K., Sonoda, I., & Satoh, H. (2008). Changes in mercury concentrations of segmental maternal hair during gestation and their correlations with other biomarkers of fetal exposure to methylmercury in the Japanese population. Environ Res, 106(2), 270-276. Schuurs, A. H. (1999). Reproductive toxicity of occupational mercury. A review of the literature. J Dent, 27(4), 249-256. Sen, J., & Chaudhuri, A. B. (2008). Arsenic exposure through drinking water and its effect on pregnancy outcome in Bengali women. Arh Hig Rada Toksikol, 59(4), 271-275. Sharara, F. I., Seifer, D. B., & Flaws, J. A. (1998). Environmental toxicants and female reproduction. Fertil Steril, 70(4), 613-622. Shimbo, S., Zhang, Z. W., Moon, C. S., Watanabe, T., Nakatsuka, H., Matsuda-Inoguchi, N., et al. (2000). Correlation between urine and blood concentrations, and dietary intake of cadmium and lead among women in the general population of Japan. Int Arch Occup Environ Health, 73(3), 163-170. Tian, L. L., Zhao, Y. C., Wang, X. C., Gu, J. L., Sun, Z. J., Zhang, Y. L., et al. (2009). Effects of Gestational Cadmium Exposure on Pregnancy Outcome and Development in the Offspring at Age 4.5 Years. Biol Trace Elem Res. Tolstrup, J. S., Kjaer, S. K., Holst, C., Sharif, H., Munk, C., Osler, M., et al. (2003). Alcohol use as predictor for infertility in a representative population of Danish women. Acta Obstet Gynecol Scand, 82(8), 744-749. Triche, E. W., & Hossain, N. (2007). Environmental factors implicated in the causation of adverse pregnancy outcome. Semin Perinatol, 31(4), 240-242. Wang, X., & Tian, J. (2004). Health risks related to residential exposure to cadmium in Zhenhe County, China. Arch Environ Health, 59(6), 324-330. WHO. (1987). Infections, pregnancies, and infertility:perspectives on prevention. Fertil. Steril., 47, 964–968. 張明揚. (2003). 不孕症及生殖內分泌學. 合記圖書出版社. 楊友仕. (1999). 生殖內分泌及不孕症概要. 健康文化事業股份有限公司. 劉佩玲. (2005). 胎盤與臍帶血汞濃度之相關研究. 碩士論文. 賴朝宏. (1997). 不孕症及其治療. 聯經出版事業公司. 近年已知環境污染物可能造成人類的生殖危害，非必需微量元素的高低可能影響不孕的發生。本研究設計為橫斷性研究，以不孕和懷孕婦女血中金屬（鉛、鎘、汞、砷）濃度和髮汞濃度作為婦女金屬暴露之生物指標，分析不孕症與正常懷孕婦女血液非必需微量元素濃度及髮汞濃度，探討體內金屬濃度與女性不孕之相關性，進而分析造成女性不孕相關危險因子。研究期間為2008年8月至2010年3月，於台北某醫院進行收樣，個案為不孕婦女組384位，懷孕婦女組58位，收集血液和頭髮，並進行基本資料與問卷訪視，分析血液中鉛、鎘、汞、砷濃度，其中鉛、鎘、砷濃度使用感應耦合電漿質譜儀(Inductively Coupled Plasma Mass Spectrometry)分析，血汞與髮汞濃度使用汞分析儀(Mercury Analysis System)分析。結果發現不孕組髮汞幾何平均濃度為1.73±0.08 ppm，懷孕婦女則為1.56± 0.18 ppm。血汞幾何平均濃度為5.90±0.25 ppb，鉛為15.89±0.40 ppb，鎘為1.31±0.04 ppb，砷為12.99±0.27 ppb；懷孕婦女血汞的幾何平均濃度為7.28±0.47 ppb，鉛為11.90±0.63 ppb，鎘為1.35±0.04 ppb，砷為11.27±0.38 ppb。邏輯斯複迴歸模式中顯示喝酒習慣、運動習慣、血鉛濃度與血砷濃度與婦女發生不孕風險達統計上的顯著相關。有喝酒習慣的婦女比起沒有者，發生不孕風險為3.04倍(AOR=3.04, C.I=1.02-9.01)，沒有運動習慣的婦女比起有運動習慣者發生不孕風險為12.57倍(AOR=12.57, C.I=3.54-44.65)。當婦女血鉛濃度≧15.47 ppb比血鉛濃度＜15.47 ppb婦女發生不孕風險為2.19倍(AOR=2.19, C.I=1.02-4.69)，另外婦女血砷濃度≧12.86 ppb比血砷濃度＜12.86 ppb者，發生不孕的風險為4.48 倍(AOR=4.48, C.I=1.96-10.21)。本研究發現婦女的低血鉛濃度、低血砷濃度、沒有運動習慣和有喝酒習慣都是造成女性發生不孕的危險因子。 Objective This study investigated the relationship between metals exposure and relevant factors risk of infertility in women. Design Cross-sectional study. Sample Study participants consisted of 384 cases recruited at the center for reproductive medicine and infertility and 58 controls at the department of gynecology and obstetrics in Taipei, Taiwan. Methods A total of 384 participants were recruited from a hospital and provided written informed consent between August 2008 and March 2010. The participants were interviewed face-to-face by a trained interviewer who collected information about sociodemographic characteristics, occupation, pregnancy and reproductive history, fish intake, and other lifestyle characteristics. Mercury concentrations in blood and hair were determined with a mercury analyzer (HG-310; Hiranuma, Mito, Japan). Lead, cadmium, and arsenic concentrations in blood were measured by inductively coupled plasma mass spectrometry (ICP-MS; Thermo X-series II). Results and Discussion The geometric mean concentration in blood was mercury: 5.90±0.25 ppb, lead: 15.89±0.40 ppb, cadmium: 1.31±0.04 ppb, arsenic: 12.99±0.27 ppb respectively for the infertility women and mercury: 7.28±0.47 ppb, lead: 11.90±0.63 ppb, cadmium 1.35±0.04 ppb, arsenic: 11.27±0.38 ppb for the fertility women. The geometric mean hair mercury concentration was 1.73±0.08 and 1.56± 0.18 ppm for the infertility and fertility women. A multiple logistic regression model is shown that women with drinking habits were associated with a 3.04 fold risk for infertility (adjusted odds ratio = 3.04, 95%C.I = 1.02-9.01). Women without exercising habits were associated with 12.57 fold risk for infertility (adjusted odds ratio = 12.57, 95%C.I = 3.54-44.65). Compare to women with blood lead level ≧15.47 ppb could cause the 2.19 fold for infertility (adjusted odds ratio = 2.19, 95%C.I = 1.02-4.69). Women with blood arsenic level ≧12.86 ppb, women with blood arsenic level ＜12.86 ppb were associated with a 4.48 fold risk for infertility (adjusted odds ratio = 4.48, 95%CI = 1.96-10.21). These findings suggest an important role of very low blood lead level, blood arsenic level, without exercising habits and with drinking habits in the risk of infertility in women.