Environmental Health Science and Research Bureau, Health Canada, AL: 2203 B, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, K1Y 0M1, Canada.
Environmental Health Science and Research Bureau, Health Canada, AL: 2203 B, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, K1Y 0M1, Canada.
Environ Pollut. 2020 Aug;263(Pt A):114602. doi: 10.1016/j.envpol.2020.114602. Epub 2020 Apr 16.
In previous studies, the total content of urinary phthalate metabolites was commonly used to evaluate human exposure to phthalates. However, phthalate metabolites are mainly present in urine in two forms, conjugated and free. These metabolite forms in urine are more relevant to the biotransformation pathways of the phthalates in humans. Therefore, the concentration of these forms is more relevant to exposure related health outcomes than total content. In this study, instead of measuring total content, the free- and conjugated-form concentrations of phthalate metabolites in the urine of fertile and infertile men were measured. The main metabolites in urine of both groups are monoethyl phthalate (MEP) and the di-(2-ethylhexyl) phthalate (DEHP) metabolites. The geometric means of their both conjugated- and free-forms in the infertile group were higher than in the fertile group, specifically, 24.3 and 43.4 μg/g creatinine vs 8.5 and 28.9 μg/g creatinine, respectively, for MEP, and 50.0 and 9.1 μg/g creatinine vs 39.1 and 8.4 μg/g creatinine, respectively for total DEHP metabolites. We investigated the correlations of free- and conjugated-form phthalate metabolite concentrations between the infertile and fertile group as well as among different phthalate metabolites. The results showed that there was a statistically significant difference between the infertile and fertile group for monobenzyl phthalate (MBzP) in both free-form and conjugated-form. However, there was only a statistically significant difference between the two groups for conjugated-form MEP and MEHP, and no statistically significant difference between the two groups for free-form MEP and MEHP. The results of the Pearson correlation test revealed that the correlations between DEHP metabolites and the correlations between mid-sized phthalate metabolites (mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP) and mono-benzyl phthalate (MBzP)) were stronger than between these two clusters of metabolites. This study is the first attempt to examine possible effects of conjugated-form concentrations of phthalate metabolites on human fertility. The results of this study suggest that conjugated-form and free-form concentrations of urinary phthalate metabolites may be appropriate biomarkers for assessing human exposure to phthalates and association with health outcomes.
在之前的研究中，通常使用尿中邻苯二甲酸酯代谢物的总量来评估人体对邻苯二甲酸酯的暴露情况。然而，尿中邻苯二甲酸酯代谢物主要以两种形式存在，即结合型和游离型。这些代谢物形式在尿液中与邻苯二甲酸酯在人体内的生物转化途径更为相关。因此，这些形式的浓度与暴露相关的健康结果更为相关，而不是总量。在这项研究中，我们没有测量邻苯二甲酸酯代谢物的总量，而是测量了生育能力正常男性和生育能力异常男性尿液中邻苯二甲酸酯代谢物的游离型和结合型浓度。两组尿液中的主要代谢物均为单乙基邻苯二甲酸酯（MEP）和二-(2-乙基己基)邻苯二甲酸酯（DEHP）代谢物。与生育能力正常组相比，生育能力异常组的游离型和结合型 MEP 及其 DEHP 代谢物的几何平均值均较高，分别为 24.3 和 43.4μg/g 肌酐与 8.5 和 28.9μg/g 肌酐，50.0 和 9.1μg/g 肌酐与 39.1 和 8.4μg/g 肌酐。我们研究了不育组和生育能力正常组之间以及不同邻苯二甲酸酯代谢物之间游离型和结合型邻苯二甲酸酯代谢物浓度的相关性。结果表明，游离型和结合型单苄基邻苯二甲酸酯（MBzP）在不育组和生育能力正常组之间存在统计学差异。然而，只有游离型 MEP 和 MEHP 以及结合型 MEP 在两组之间存在统计学差异，而游离型 MEHP 在两组之间没有统计学差异。皮尔逊相关检验结果表明，DEHP 代谢物之间以及中分子量邻苯二甲酸酯代谢物（单正丁基邻苯二甲酸酯（MnBP）、单异丁基邻苯二甲酸酯（MiBP）和单苄基邻苯二甲酸酯（MBzP））之间的相关性比这两个代谢物群之间的相关性更强。这项研究首次尝试检验邻苯二甲酸酯代谢物结合型浓度对人类生育能力的可能影响。本研究结果表明，尿中邻苯二甲酸酯代谢物的游离型和结合型浓度可能是评估人体邻苯二甲酸酯暴露情况和与健康结果相关性的合适生物标志物。
