Urinary phthalate metabolites in association with semen parameters and reproductive hormones among fertile and infertile Iranian males

학위논문(석사) -- 서울대학교대학원 : 보건대학원 환경보건학과, 2022.2. Kyungho Choi.Exposure to phthalates has been found to be associated with adverse effects on male reproductive function. However, the findings in human population are inconsistent. We examined the associations of urinary phthalate metabolites with semen quality and reproductive hormones among Iranian male population (n=178) who visited an infertility center, Kermanshah, Iran. One urine sample, one blood sample and one semen sample were collected from each male and semen quality parameters and serum reproductive hormone levels were examined. Concentrations of 8 commonly used phthalate metabolites (MMP, MEP, MBP, MiBP, MBzP, MEHP, MEOHP and MEHHP) were assessed in urine using gas chromatography mass spectrometry. The present study population exhibited generally higher levels of MEHHP, MEOHP and MEHP (mean: 71.5 g/L, 59.8 g/L and 61.9 g/L, respectively) among the measured phthlate metabolites. Significant negative association was observed between urinary concentrations of DEHP and DiBP metabolites and sperm quality parameters such as concentration and motility (P < 0.05). MEHHP also had a negative association with sperm normal morphology (P < 0.05). The semen parameters and urinary phthalates levels associations remained significant (MEOHP) or suggestive after using logistic regression models. Interestingly, urinary MEHHP was associated with increasing serum total testosterone (TT) (P < 0.05) in total population (n = 178), but the significance disappeared among subgroup of males with abnormal semen quality parameters (n = 84). Estimated daily intake of DEHP (16.74 µg/kg/ day), when compared with reference dose for anti-androgenic effect (RfD_AA), is noteworthy as its HQ was estimated at an arithmetic mean of 1.6740. Our observations show that DEHP exposure may be associated with infertlity of Iranian male at the current level of exposure, while confirmation would be warranted in other similar populations.Table of Contents 1. Introduction 5 2. Materials and Method 7 2.1. Study population and sample collection 7 2.2. Measurement of semen/hormones outcomes 7 2.3. Analysis of urinary mPAEs 8 2.4. Quality assurance and quality control (QA/QC) 9 2.5. Statistical analysis 9 2.6. Exposure and risk assessment 11 2.7. Cumulative risk assessment 11 3. Results and Discussion 13 3.1. Study population 13 3.2. Semen parameters and reproductive hormones outcome 15 3.3. Levels of urinary mPAEs 17 3.4. Occurrence reported in other populations 21 3.5. Correlations among the urinary mPAEs 25 3.6. Associations between urinary mPAEs and semen quality parameters 27 3.7. Associations between urinary mPAEs and reproductive hormones 33 3.8. Exposure and risk assessment 35 4. Conclusion 41 References 42석