The Effects Of Phthalate Exposure On Aromatase Expression In Adult Men

Abstract

Introduction: The objectives of present study are to assess the associations among urinary phthalate metabolites levels, reproductive hormones and serum aromatase concentrations in adult men, and to explore the active mechanisms of phthalate exposure on aromatase expression in adult men. Methods: 298 subjects were recruited from the infertile clinic of National Cheng Kung University Hospital and AN-AN Women and Children Clinic, including 83 infertile men with abnormal semen quality (Group 1), 176 infertile men with normal semen quality (Group 2), and 39 fertile men (Group 3). After signed informed consent, the present study conducted through the questionnaire interview, determination of reproductive hormones, aromatase, and urinary phthalate metabolites. Urinary phthalate metabolites were analyzed with HPLC-MS/MS. Results: Urinary MMP, MEP, MiBP, MEHHP, MECPP, MEOHP, MINP and MIDP in Group 1 were higher than Group 2 and 3. Urinary MINP showed significant difference among three groups. Estradiol and serum aromatase concentrations in Group 1 were significant higher than Group 2 and 3 respectively. The significant increasing trends were found in estradiol levels and serum aromatase concentrations among the three groups respectively. After adjusting for age, BMI and season of blood drawing, urinary MMP, MEP and MEOHP were significantly positively associated with estradiol. Urinary MMP and MEP were significantly negatively associated with the TT:E2 ratio. Urinary MiBP, MnBP, MEHHP, MECPP, MEOHP were significantly positively associated with serum aromatase concentrations. The infertile men with abnormal semen quality had higher estrogen receptor binding effect and androgen receptor antagonistic effect than infertile men with normal semen quality and fertile men. Conclusion: phthalate exposure may increase serum aromatase concentrations, upregulation of CYP19a1 gene for the estrogen receptors, resulting in abnormally increase of estradiol levels by an estrogenic mode of action.