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Phthalates Induce Androgenic Effects at Exposure Levels That Can Be Environmentally Relevant in Humans
Environmental Science & Technology Letters ( IF 8.9 ) Pub Date : 2018-04-17 , DOI: 10.1021/acs.estlett.8b00138
Meiping Tian 1, 2 , Liangpo Liu 1 , Heng Wang 1 , Xiaofei Wang 1 , Francis L. Martin 3 , Jie Zhang 1 , Qingyu Huang 1 , Heqing Shen 1
Affiliation  

Although anti-androgenic activity of various lipophilic chain phthalate acid esters (PAEs) has been reported in high-dose animal studies, their male reproductive risk remains a matter of debate because of conflicting epidemiological observations. Recently, we showed that PAEs acted as a preventative factor in male infertility, which implies these chemicals are androgenic in human steroidogenesis. To verify the androgenic observation, a reproductive age healthy male cohort (n = 84) was recruited by following a cross-sectional study design, in which infertility or clinical selection-introduced bias was avoided. Urine was used for both PAE exposure monitoring and androgen measurements, and sampling uncertainty was greatly reduced. Eight selected metabolites (i.e., MMP, MEP, MBP, MEHP, MBzP, MEHHP, MECPP, and MEOHP) and two androgens, i.e., androstenedione (ASD) and testosterone, were measured by using HPLC–MS/MS. Except for MBzP, the selected phthalates can be detected in all samples at concentrations (median [5th–95th percentile]) of 36.4 [2.0–261.0], 36.7 [5.6–318.5], 75.3 [13.1–301.0], 3.2 [1.1–10.2], 3.8 [0.6–11.9], 13.6 [1.6–51.1], and 7.4 [0.9–31.8] ng/mL for MMP, MEP, MBP, MEHP, MEOHP, MECPP, and MEHHP, respectively. Urinary PAE metabolites generally correlated with ASD and testosterone in positive ways; the trends are most significant for MMP, MEP, MBP, and ∑DEHP versus ASD and for ∑DEHP versus testosterone. This study reveals that the phenotypic effect of our participants’ exposure to PAEs at the typical environmental relevant exposure level is androgenic, which counters the notion of the well-accepted anti-androgenic effect.

中文翻译:

邻苯二甲酸酯在与人体环境相关的暴露水平下会引起雄激素作用

尽管在高剂量动物研究中已报道了各种亲脂性链状邻苯二甲酸酯(PAE)的抗雄激素活性,但由于流行病学观察结果相互矛盾,其雄性生殖风险仍然存在争议。最近,我们表明PAEs可以作为男性不育症的预防因素,这意味着这些化学物质在人类类固醇生成中具有雄激素作用。为了验证雄激素的观察结果,一个生育年龄健康的男性队列(n= 84)是通过采用横断面研究设计招募的,其中避免了不孕症或临床选择引起的偏倚。尿液用于PAE暴露监测和雄激素测量,大大降低了采样不确定性。使用HPLC-MS / MS测定了八种选定的代谢物(即MMP,MEP,MBP,MEHP,MBzP,MEHHP,MECPP和MEOHP)和两种雄激素,即雄烯二酮(ASD)和睾丸激素。除MBzP外,所有样品中所检测的邻苯二甲酸盐的浓度(中位[5–95%]为36.4 [2.0–261.0],36.7 [5.6–318.5],75.3 [13.1–301.0],3.2 [1.1–对于MMP,MEP,MBP,MEHP,MEOHP,MECPP和MEHHP,分别为10.2],3.8 [0.6-11.9],13.6 [1.6-51.1]和7.4 [0.9-31.8] ng / mL。尿PAE代谢物通常与ASD和睾丸激素呈正相关。MMP,MEP,MBP和∑DEHP与ASD以及∑DEHP与睾丸激素的趋势最为明显。这项研究表明,我们的参与者在典型的环境相关暴露水平下暴露于PAEs的表型效应是雄激素的,这与公认的抗雄激素作用的概念背道而驰。
更新日期:2018-04-17
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