Interactions between Urinary 4-tert-Octylphenol Levels and Metabolism Enzyme Gene Variants on Idiopathic Male Infertility |
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| Authors: | Yufeng Qin Minjian Chen Wei Wu Bin Xu Rong Tang Xiaojiao Chen Guizhen Du Chuncheng Lu John D. Meeker Zuomin Zhou Yankai Xia Xinru Wang |
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| Affiliation: | 1. State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.; 2. Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.; 3. Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, United States of America.; University of Hawaii at Manoa, John A. Burns School of Medicine, United States of America, |
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| Abstract: | Octylphenol (OP) and Trichlorophenol (TCP) act as endocrine disruptors and have effects on male reproductive function. We studied the interactions between 4-tert-Octylphenol (4-t-OP), 4-n- Octylphenol (4-n-OP), 2,3,4-Trichlorophenol (2,3,4-TCP), 2,4,5-Trichlorophenol (2,4,5-TCP) urinary exposure levels and polymorphisms in selected xenobiotic metabolism enzyme genes among 589 idiopathic male infertile patients and 396 controls in a Han-Chinese population. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to measure alkylphenols and chlorophenols in urine. Polymorphisms were genotyped using the SNPstream platform and the Taqman method. Among four phenols that were detected, we found that only exposure to 4-t-OP increased the risk of male infertility (Ptrend = 1.70×10−7). The strongest interaction was between 4-t-OP and rs4918758 in CYP2C9 (Pinter = 6.05×10−7). It presented a significant monotonic increase in risk estimates for male infertility with increasing 4-t-OP exposure levels among men with TC/CC genotype (low level compared with non-exposed, odds ratio (OR) = 2.26, 95% confidence intervals (CI) = 1.06, 4.83; high level compared with non-exposed, OR = 9.22, 95% CI = 2.78, 30.59), but no associations observed among men with TT genotype. We also found interactions between 4-t-OP and rs4986894 in CYP2C19, and between rs1048943 in CYP1A1, on male infertile risk (Pinter = 8.09×10−7, Pinter = 3.73×10−4, respectively).We observed notable interactions between 4-t-OP exposure and metabolism enzyme gene polymorphisms on idiopathic infertility in Han-Chinese men. |
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