Combined effects of urinary phytoestrogens metabolites and polymorphisms in metabolic enzyme gene on idiopathic male infertility.
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.
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 818 East Tianyuan Road, Nanjing, 211166, China.
Yufeng
Y
Qin
Guizhen
G
Du
Minjian
M
Chen
Weiyue
W
Hu
Chuncheng
C
Lu
Wei
W
Wu
Bo
B
Hang
Zuomin
Z
Zhou
Xinru
X
Wang
Yankai
Y
Xia
D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001711:Biotransformation; D002072:Butylene Glycols / Q000009:adverse effects / Q000378:metabolism / Q000652:urine*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D006801:Humans; D007248:Infertility, Male / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism* / Q000652:urine; D017705:Lignans / Q000009:adverse effects / Q000378:metabolism / Q000652:urine*; D008297:Male; D048789:Phytoestrogens / Q000009:adverse effects / Q000378:metabolism / Q000652:urine*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D002072:Butylene Glycols; D017705:Lignans; D048789:Phytoestrogens; C569463:CYP1A1 protein, human; C585599:CYP2B6 protein, human; D019363:Cytochrome P-450 CYP1A1; D065702:Cytochrome P-450 CYP2B6; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; C060283:secoisolariciresinol