Phthalates might interfere with testicular function by reducing testosterone and insulin-like factor 3 levels
Phthalates might interfere with testicular function by reducing testosterone and insulin-like factor 3 levels
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DOI：
10.1093/humrep/dev225
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发表时间：
2015-11-01
影响因子：
6.1
通讯作者：
Lee, Ching-Chang
中科院分区：
文献类型：
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作者：
Chang, Wei-Hsiang;Li, Sih-Syuan;Lee, Ching-Chang
研究问题：邻苯二甲酸酯是否会通过下调睾酮和胰岛素样因子3（INSL 3）的分泌而导致男性生殖激素失衡？简要答复：我们的研究表明，暴露于邻苯二甲酸酯与成年男性睾酮和INSL 3分泌减少有关。已知：有证据表明，暴露于邻苯二甲酸酯，一种丰富的工业增塑剂，对睾酮的生物合成产生负面影响，但对男性的机制知之甚少。暴露于邻苯二甲酸酯会降低睾丸激素和INSL 3水平的假设，这是Leydig细胞功能的标志，研究设计，规模，持续时间：这项病例对照研究的176名男性从2010年到2012年。不孕症男性通过台湾不孕症诊所招募，生育男性从分娩准备班招募，所有人都根据世界卫生组织对不孕症的定义和产科医生的诊断进行分类。测量了11种邻苯二甲酸酯代谢物的尿液浓度，沿着血清FSH、LH、总睾酮（TT）、雌二醇，性激素结合球蛋白和抑制素B。计算雄激素状态指数，包括游离睾酮（fT）和游离雄激素指数（FAI）。使用放射免疫测定法评价循环INSL 3水平。非参数分析，趋势检验和线性回归models.Main结果和机会的作用：尿单正丁基邻苯二甲酸酯（MnBP），单-（2-乙基己基）邻苯二甲酸酯（MEHP）和单-2-乙基-5-羧基戊基邻苯二甲酸酯显着高于不育男性。不育男性血清抑制素B、抑制素B：FSH比值、TT：LH比值和INSL 3均显著降低。在控制潜在混杂因素的多元回归模型中，尿中邻苯二甲酸单甲酯（MMP）、邻苯二甲酸单异丁酯（MiBP）、MEHP、MEHP%水平与血清TT呈负相关（分别为P = 0.001、0.007、0.042和0.012）。尿中MiBP、邻苯二甲酸单苄酯（MBzP）、MEHP、MEHP%与血清fT呈负相关（P值分别为0.028、0.017、0.045和0.027）;尿MMP、MEHP、MEHP%水平与TT：LH比值之间尿MMP、MiBP、MnBP、MBzP、MEHP与FAI之间的差异有统计学意义（P值分别为0.002、0.008、0.037、0.028、0.042和0.016）。尿MBzP和MEHP%与血清INSL 3降低呈负相关（P = 0.049，
STUDY QUESTION: Do phthalates create a male reproductive hormone imbalance by down-regulating the secretion of testosterone and insulin-like factor 3 (INSL3)?SUMMARY ANSWER: Our study suggests that exposure to phthalates is related to a reduction in the secretion of testosterone and INSL3 in adult males.WHAT IS KNOWN ALREADY: There is evidence that exposure to phthalates, an abundant group of industrial plasticizers, negatively affects testosterone biosynthesis, but little is known about the mechanism in men. The hypothesis that exposure to phthalates reduces the levels of testosterone and INSL3, a marker of Leydig cell function, is underexplored.STUDY DESIGN, SIZE, DURATION: This case-control study of 176 men ran from 2010 to 2012. Infertile men were recruited through infertility clinics in Taiwan, fertile men were recruited from childbirth preparation classes and all were categorized based on the World Health Organization definition of infertility and by the diagnoses of obstetricians.PARTICIPANTS/MATERIALS, SETTING, METHODS: Urinary concentrations of 11 phthalate metabolites were measured, along with serum levels of FSH, LH, total testosterone (TT), estradiol, sex hormone-binding globulin and Inhibin B. Androgen status indices including free testosterone (fT) and the free androgen index (FAI) were calculated. The circulating INSL3 level was evaluated using a radioimmunoassay. Non-parametric analyses, trend tests and linear regression models were used.MAIN RESULTS AND THE ROLE OF CHANCE: Urinary mono-n-butyl phthalate (MnBP), mono-(2-ethylhexyl) phthalate (MEHP) and mono-2-ethyl-5-carboxypentyl phthalate were significantly higher in infertile than in fertile men. Serum Inhibin B, the Inhibin B : FSH ratio, the TT : LH ratio and INSL3 were significantly lower in infertile men. In multiple regression models controlled for potential confounders, there is an inverse association between urinary levels of mono-methyl phthalate (MMP), mono-iso-butyl phthalate (MiBP), MEHP, MEHP% and serum TT (P = 0.001, 0.007, 0.042 and 0.012, respectively). The inverse associations were also found between urinary levels of MiBP, monobenzyl phthalate (MBzP), MEHP, MEHP% and serum fT (P = 0.028, 0.017, 0.045 and 0.027, respectively); between urinary levels of MMP, MEHP, MEHP% and the TT : LH ratio (P = 0.004, 0.029 and 0.039, respectively); between urinary levels of MMP, MiBP, MnBP, MBzP, MEHP and the FAI (P = 0.002, 0.008, 0.037, 0.028, 0.042 and 0.016, respectively). Urinary MBzP and MEHP% were negatively associated with a decrease in serum INSL3 (P = 0.049 and