Interactions between Urinary 4-tert-Octylphenol Levels and Metabolism Enzyme Gene Variants on Idiopathic Male Infertility

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 (P trend = 1.70×10−7). The strongest interaction was between 4-t-OP and rs4918758 in CYP2C9 (P inter = 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 (P inter = 8.09×10−7, P inter = 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.

Urinary Levels of 4-Nonylphenol and 4-t-Octylphenol in a Representative Sample of the Korean Adult Population

“…A possible factor influencing the difference is that our study had a lower LOD (0.05 ng/mL) and higher percentage greater than the LOD (91.8%) than did the NHANES study (LOD = 0.2 ng/mL, percentage greater than the LOD, 57.4%), which would yield more precise percentiles and geometric means compared with studies with a higher LOD. Other studies have reported that the geometric mean 4-t-OP concentrations in the urine of Chinese men and women were 0.60 ng/mL and 0.90 ng/mL, respectively [ 12 , 25 ], which is similar to those of the Korean general population shown in this study.…”

Job-exposure matrix for the assessment of alkylphenolic compounds

“…To the best of our knowledge, alkylphenolic compounds have been linked to certain maternal exposures leading to health outcomes in their offspring,26–29 congenital heart defects,30 31 male infertility32 and certain types of neoplasms33–36 in epidemiological studies among humans. Studies have usually evaluated exposure to alkylphenols in urine samples26–28 32 35–37 or through occupational studies using JEMs 29–31 33 34. The evaluation of alkylphenolic compounds in epidemiological studies is hampered by limitations on the available laboratory tests to assess levels on blood serum or plasma samples, which are generally collected in epidemiological studies.…”

The role of hysteroscopy in unexplained infertility

“…The level of sex hormones thus lowers and this produces menstrual irregularities and anovulation. In humans, moreover, it would appear that exposure to certain endocrine disruptors (4-tertoctylphenol) would alter the functionality of sperm [28]. In the literature emerges that research on idiopathic infertility is still incomplete.…”