探討血液中金屬濃度與男性不孕症之關係
The relationship between metals concentration in blood and male infertility
中文摘要
目前已知許多種環境物質會影響生物體的生殖能力及性表現。過去二十年間工業
國家不孕症盛行率由8%增加至 15%的情況，重金屬被認為是造成男性生殖能
力下降的重要因子之一。鉛（Pb）是環境中普遍存在的污染物質，過去的流行 病學研究報告指出職業上的鉛暴露會使男性生殖功能產生不良影響；鎘（Cd）
則是在動物實驗中被證實會損害男性生殖系統。另一方面，有研究證實硒（Se）
對於老鼠的睪丸正常生長及精子熟成作用（spermatogenesis）是必需的元素。
另有研究指出重金屬會造成脂質的過氧化作用，且與精液的異常有所關聯。因
此，本研究之目的為，（1）探討男性不孕症患者之基本特性；（2）分析並了解
血液中金屬濃度與不孕男性精液品質之關係；（3）探討其他影響因子對金屬暴
露程度與男性不孕間之交互作用。利用問卷訪視不孕症男性，收集其血液測定血 中金屬、脂質過氧化相關物質濃度及四種男性生殖相關荷爾蒙，並記錄精液分析 結果。
研究結果顯示，最近四年某教學醫院不孕症患者296 名，將精子濃度分為 0、
1~5、6~19 及大於等於 20 million/ml 四組，其年齡（p=.001）、黃體激素
（LH）（p=.001）及濾泡激素（FSH）（p=.000）平均值之間均有顯著差異。
而精子活動力分為0，1~49 及大於等於 50%三組，其年齡（p=.002）、黃體 激素（p=.022）及濾泡激素（p=.000）平均值之間亦呈現顯著差異。精子活 動力與年齡、睪丸尺寸及男性生殖荷爾蒙之複迴歸分析，結果顯示在相互調整後 與濾泡激素和睪丸尺寸的關係達到統計上的顯著意義（p=.019, p=.037）。在
近一年之不孕症研究個案方面，共41 位患者其臨床表徵與最近四年不孕症者之
分佈相似，而其血中鉛濃度平均為19.90 ±3.98 µg/L，血中鎘濃度平均為 1.80
±0.88 µg/L，而血中硒濃度平均為 97.87 ±2.61µg/L。精子濃度與年齡、血 中鉛和硒濃度、睪丸尺寸、濾泡激素、睪固酮（testosteron）、脂質過氧化產 物（MDA）、麩胱甘 （GSH）及超氧化物歧化 （SOD）之複迴歸分析，結 果發現濾泡激素及睪固酮與精子濃度呈正向關係，且達統計上顯著意義
（p=.014, p=.024），血鉛濃度與精子濃度呈現負向關係，而血硒和精子濃度 呈正向關係，但都未達統計上顯著意義性。精子活動力與年齡、血中鉛、鎘和硒 濃度及睪固酮之複迴歸分析，結果顯示精子活動力與血鉛及血鎘濃度均呈現負向 關係，與睪固酮呈正向關係，但仍都未達統計上顯著意義性，血硒則呈現邊緣性 統計上保護作用，而年齡的增加及睪丸的萎縮則顯著降低精子活動力。由於本研 究個案樣本數過小，血中金屬濃度與精液分析結果未能有明顯的劑量反應關係，
故建議收集更多的樣本並增加健康對照組及高暴露組，再進一步深入的探討。
英文摘要
Environmental factors have been suggested to play a role in human infertility. The prevalence of infertility has increased from 8 to 15% over the past 2 decades in industrialized countries, with heavy metals being implicated in male reproductive dysfunction. Lead (Pb) is an environmental pollutant shown to adversely affect male reproductive functions. Cadmium (Cd) has been reported to affect the reproductive systems of male animals. On the other side, Selenium (Se) is required for normal testicular development and spermatogenesis in rats. Studies have shown that heavy metals produce lipid peroxidation, and this phenomenon is associated with improper semen quality. Therefore, the aim of this work were: (1) to explore the basic features in male infertility; (2) to analyze and find out the relationship between metals
concentration in blood and semen analysis in male infertility; (3) to explore the interaction of other risk factors with metals exposure and male infertility.
We divided sperm count of infertile men 296 in the latest four years into four groups:
0, 1~5, 6~19 and more then 20 million/ml. The average age (p=.001), concentrations of luteinizing hormone（LH）(p=.001) and follicle-stimulating hormone（FSH）(p=.000) of four groups were statistically significant differences. We also divided infertile men’s sperm motility into three groups: 0, 1~49 and more then 50%. The average age (p=.002), concentrations of LH (p=.002) and FSH (p=.022) of three groups were significant differences, too. In the multiple linear regression, the result showed that sperm motility was significantly associated with FSH (p=.019) and testis sizes (p=.037) adjusted by age.
A total of 41 infertile men’s bloods in a latest year were collected, and the clinical features of these patients are similar to before. The average concentration of blood lead, cadmium and selenium is 19.90 ± 3.98, 1.80 ± 0.88 and 97.87 ± 2.61 μg/L respectively. In the multiple regression, the result showed positive impact of sperm count with FSH (p=.014)and testosterone (p=.024), adjusted by age, blood lead, blood selenium, testis sides, malondialdehyde（MDA）, glutathione disulfide（GSH）and superoxide dismutase（SOD）. A negative relation of sperm count with blood lead and a positive relation with blood selenium, but both of them were non-significance. In other regression models, blood lead and blood cadmium level were negatively, and testosterone were positively related to sperm motility with statistical non-significance.
A significance decrease of sperm motility was found by aging and testis atrophy, and marginal statistical significant protection effect were also found by blood selenium increasing. Subjects of non-infertility group and high exposure group should be collected for the further exploration.
