4-Nonylphenol Exposure, Diet, Life Style and Reproductive Health

前言:壬基苯酚(4-nonylphenol，NP)為烷基酚類化合物生物分解後的主要產物，被排放到環境中不易被微生物分解，若經由食物鏈為人所攝取，其本身的毒性並不高，但結構與雌性激素類似，已在魚類、鳥類和哺乳動物實驗中證實為環境荷爾蒙之一。人類有極多機會可透過食物鏈攝取NP，然而，人體暴露於壬基苯酚之健康效應的研究仍相當有限，且沒有研究探討過NP暴露對人類生殖健康之影響。本研究以橫斷式研究法探討人體尿中壬基苯酚暴露與飲食習慣之相關性，以及NP暴露對不孕治療男性精液品質之影響，最後並評估NP在親子代間尿液與血液中之垂直分布。 方法:經過同意，我們招募了67對不孕治療夫妻及132名正常孕婦及新生兒為研究對象，收集其血液、尿液樣本，收集的尿液樣本以酸洗過之容器盛裝且經creatinine校正，並於-20℃保存。血液與尿液樣本先進行固相萃取純化前處理，再以高效能液相層析儀(HPLC)配合螢光偵測器進行NP濃度測定。探討67對夫妻與132對母子壬基苯酚的暴露狀態與飲食習慣之相關性，以及NP在母體與子代間之垂直分布狀況，並比較不孕治療孕婦與一般產婦體內NP暴露之差異。並對67位不孕治療男性精液品質評估其精蟲數(106/ml)及精蟲活動度(%)與其尿中NP濃度之關聯性。 結果: 非本國籍樣本的尿中與血液壬基苯酚濃度高於本國籍。不論正常產婦或不孕治療孕婦，年齡與尿液及血液壬基苯酚濃度無顯著差異，也發現運動、服藥、保健食品攝取、飲酒、嚼檳榔、喝咖啡、飲茶等生活習慣與體內壬基苯酚濃度的高低無關。然而，常攝取全脂奶之產婦相較於較少攝取者有比較高的血中NP濃度(odds ratio = 4.48, 95% CI = 2.12-9.48)，脫脂奶之攝取也有相同趨勢(odds ratio = 2.32, 95% CI = 1.15-4.67)其餘飲食習慣與血液及尿液壬基苯酚濃度高低無關。 相對於生殖能力正常之產婦，不孕症治療孕婦尿中壬基苯酚濃度明顯較高(16.10 + 11.33 vs. 4.32 + 3.81 ng/ml, p < 0.001)。對應於中位數，不孕治療者尿中肌酸酐校正前為正常產婦的的13.90倍，校正後為8.60倍。服藥與喝咖啡在不孕治療婦女間亦具有較高之尿中NP濃度。不孕治療夫妻之間尿中壬基苯酚濃度有顯著相關(r = 0.31, p <0.05)，尿中NP濃度與各類飲食攝取在夫妻間均呈現高度相關。 與正常產婦相似，不孕治療夫妻攝取較多全脂奶者其尿中NP濃度為不常攝取者之4.33倍（p < 0.05）。尿中壬基苯酚濃度愈高，精蟲濃度愈低（p < 0.001），精蟲活動度也愈差（p < 0.001）。並未有其他因子明顯影響體內精蟲濃度與精蟲活動度。母體靜脈血的壬基苯酚檢出率達82.6%，母體尿液的壬基苯酚檢出率亦相近，為82.4%。子代臍帶血的壬基苯酚檢出率為67.4%，子代尿液的壬基苯酚檢出率為72.4%。子代血液壬基苯酚濃度帄均約為母代的54%，子代尿液壬基苯酚濃度則帄均約為母代的62%。 結論:在本研究中，奶品攝取與體內壬基苯酚濃度升高有關，不孕治療夫妻之暴露量更大。NP是可能在親子間有垂直分布，NP暴露較高與精液品質之高風險有關。Preface: Nonylphenol (4-nonylphenol, NP) is the main product of biological decomposition of alkylphenol compounds. It can not be broken down easily by microorganisms in the environment. It has been confirmed by experiments on fish, birds and mammals that NP is an environmental hormone because its structure is similar to estrogen. There are plenty of chances that human may have daily intake of NP through the food chain. However, there are limited studies on human exposure of NP and No study has ever investigated the human reproductive health associated with NP exposure. In this study, we performed a cross-sectional survey to measure the NP levels in urine and blood, and its association with dietary habits, and semen quality in men. We also measured NP levels in maternal and fetal samples of urine and blood to evaluate the vertical partitioning of NP. Methods and materials: With consent, we recruited a convenient sample of 67 couples at an infertility clinic and 132 pregnant women and their newborns. Urine and blood samples were collected. The urine samples were collected with acid washed containers and creatinine correction, and stored at -20 ℃. Blood and urine samples were purified by solid phase extraction for pretreatment, following high-performance liquid chromatography (HPLC) assay, using fluorescence detector f to determine NP concentrations. Data analyses measured the association between NP levels and diet among 67 couples as well as vertical distribution of NP between 132 mothers and offsprings. We also compared NP levels in urine between women visiting the clinic for infertility treatment and women for general prenatal care. Semen quality was evaluated for 67 men by measuring sperm count (million/ml), and sperm motility (percent) associated with urinary NP levels. Results: The NP levels in both urine and blood samples were higher in foreign born women than in native women. There were no significant age-specific differences in NP levels in urine and blood samples measured for women with infertility or women for general prenatal care. We found NP levels in urine and blood samples were not associated with sports, medications, healthy food intake, alcohol consumption, chewing betel nuts, and intake of coffee and tea, etc. However, among women for general prenatal care at the clinic, those with higher intake of whole milk had higher mean blood NP level than those with lower intake (odds ratio = 4.48, 95% confidence interval 2.12 - 9.48). Similar pattern was also observed for the skim milk consumption (odds ratio = 2.32, 95% confidence interval 1.15 - 4.67). All rest of diet factors had no significant association with NP in both urine and blood samples. The mean urinary NP concentration was significantly higher in pregnant women for the infertility visit than women for the general prenatal care (16.10 + 11.33 vs. 4.32 + 3.81 ng / ml, p < 0.001). The corresponding ratios of median levels were 13.9-fold higher without adjusting creatinine levels and 8.6-fold higher with creatinine being adjusted. Medication and coffee consumption also associated with higher urinary NP in infertility women. There was no significant differences in urinary NP concentrations between husbands and wifes for infertility treatment (r = 0.31, p < 0.05). The mean NP levels were similar between these husbands and wifes measured by all types of diet and life style. Among these infertility couples, the mean urinary NP in those with higher whole milk consumption was 4.33-fold (p < 0.05) higher than those with lower consumption. Higher NP concentrations in urine samples were associated with lower sperm concentration (p < 0.001), and less sperm activity (p < 0.001). No other factors were significantly associated with sperm concentration and sperm activity. Analyzing of the maternal and childhood association in NP measures showed that the chemical was detectable in 82.6% of blood samples and 82.4% of urine samples for mothers. NP was detectable in 67.4% of cord blood samples with the mean about 54.0% of the mean of maternal level. NP was also detectable in 72.4% of urine samples of new borns, with the mean 62.0% of that of mothers (p < 0.001). Conclusion: The consumption of milk is associated with elevated NP levels intake. The exposure was greater in couples with infertility. Vertical partition of NP from pregnant womam to her fetus is likely. Higher NP exposure is associated with higher risk of impaired sperm quality