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Combined effects of urinary phytoestrogens metabolites and polymorphisms in metabolic enzyme gene on idiopathic male infertility

  • Toxicogenomics
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Abstract

Phytoestrogens are plant-derived compounds that may interact with estrogen receptors and mimic estrogenic effects. It remains unclear whether the individual variability in metabolizing phytoestrogens contributes to phytoestrogens-induced beneficial or detrimental effects. Our aim was to determine whether there is any interaction between metabolic rates (MR) of phytoestrogens and genetic polymorphisms in related xenobiotic metabolizing enzyme genes. MR was used to assess phytoestrogen exposure and individual metabolic ability. The amount of phytoestrogens in urine was measured by ultra-high performance liquid chromatography-tandem mass spectrometry in 600 idiopathic infertile male patients and 401 controls. Polymorphisms were genotyped using the SNPstream platform combined with the Taqman method. Prototypes and metabolites of secoisolariciresinol (SEC) have inverse effects on male reproduction. It was found that low MR of SEC increased the risk of male infertility (OR 2.49, 95 % CI 1.78, 3.48, P trend = 8.00 × 10−8). Novel interactions were also observed between the MR of SEC and rs1042389 in CYP2B6, rs1048943 in CYP1A1, and rs1799931 in NAT2 on male infertility (P inter = 1.06 × 10−4, 1.14 × 10−3, 3.55 × 10−3, respectively). By analyzing the relationships between urinary phytoestrogen concentrations, their metabolites and male infertility, we found that individual variability in metabolizing SEC contributed to the interpersonal differences in SEC’s effects on male reproduction.

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Acknowledgments

This study was supported by National Natural Science Foundation of China (81072328), National Science Fund for Outstanding Young Scholars (81322039), National Natural Science Foundation (31371524), Distinguished Young Scholars of Jiangsu Province (BK20130041), University Natural Science Research Project in Jiangsu Province (11KJB330001), The Program for Postgraduates Research Innovation in University of Jiangsu Province (CXZZ12-0600), and Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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There are no conflict interests to declare.

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Authors and Affiliations

  1. State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 818 East Tianyuan Road, Nanjing, 211166, China

    Yufeng Qin, Guizhen Du, Minjian Chen, Weiyue Hu, Chuncheng Lu, Wei Wu, Zuomin Zhou, Xinru Wang & Yankai Xia

  2. Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    Yufeng Qin, Guizhen Du, Minjian Chen, Weiyue Hu, Chuncheng Lu, Wei Wu, Xinru Wang & Yankai Xia

  3. Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA, 94720, USA

    Bo Hang

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  1. Yufeng Qin
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Correspondence to Yankai Xia.

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Yufeng Qin, Guizhen Du and Minjian Chen have contributed equally.

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Qin, Y., Du, G., Chen, M. et al. Combined effects of urinary phytoestrogens metabolites and polymorphisms in metabolic enzyme gene on idiopathic male infertility. Arch Toxicol 88, 1527–1536 (2014). https://doi.org/10.1007/s00204-014-1205-y

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