| Summary: | 碩士 === 國立成功大學 === 環境醫學研究所 === 101 === The prevalence of infertility was increased in recent years, and the female infertility accounted for 30%. The risk factors of female infertility were numerous and complex, including physical (age, genes, BMI etc.), psychological (stress, emotion etc.), disease (hormonal imbalance, ovulated disorder, inflammatory disease, adenomyosis, endometriosis, polycystic ovarian syndrome etc.), life style (smoking, drugs, alcohol etc.) and environmental pollutants or endocrine disruptors. Phthalate esters (PAEs) were known endocrine disrupting compounds (EDCs), and were widely used in PVC products, plastic food containers, personal care products, cosmetics and commercial products. Numerous evidences indicated that phthalates exposures cause adverse reproductive effects including increased serum estradiol, reduced progesterone levels and aromatase activity, prolonged estrous cycles, no ovulations, and some reproductive disease, and then increased the probability of infertility. However, little is known about the active mechanism and impact of PAEs on female infertility. The aim of this study was to investigate the relationship between the urinary PAE metabolites and serum reproductive hormone levels in women who seeking treatment from infertile clinics. 79 participants were recruited from Obstetrics and Gynecology clinics, National Cheng Kung University Hospital. After signing the informed consent and obstetrician diagnosis, urine and blood samples were collected and stored with phthalate free containers. Questionnaire interview were conducted for demographic characteristics and exposure profile of phthalates. Levels of PAE metabolites in urine were analyzed by HPLC/MS/MS and serum reproductive hormones were measured for all participants. All the data were integrated to explore the phthalate exposure profile, PAE metabolites, reproductive hormone levels and active mechanism of PAEs to disrupt reproductive hormones in women. The average (range) of urinary PAE metabolite levels were MEP：17.38 (1.51-740.49) µg/g-cre, MnBP：11.62 (1.84-145.83) µg/g-cre, MECPP：10.48 (1.85-293.99) µg/g-cre, MiBP：7.60 (1.39-102.86) µg/g-cre, MEOHP：7.44 (1.08-128.60) µg/g-cre, MEHHP：5.79 (0.28-211.35) µg/g-cre, MEHP：4.33 (1.08-54.68) µg/g-cre, MMP：3.31 (0.34-14.04) µg/g-cre, MBzP：1.23 (0.21-23.01) µg/g-cre, MIDP：0.42 (0.08-1.26) µg/g-cre and MINP：0.27 (0.04-1.26) µg/g-cre. MEP is the highest of the eleven measured PAEs metabolites. All subjects were classified to high and low concentration group according to the urinary MEHP concentration. The levels of MEHP, MEOHP, MBzP, MINP, MIDP, ∑DEHP and MEHP% in high concentration group were significantly higher than low concentration group. The serum free testosterone (fT) in high concentration group was significantly lower than low concentration group. The significantly positive correlation were found between inhibin B with MEOHP, MBzP, MEHP%; P4 with MEHHP, MECPP; SHBG with MEP; PRL with MECPP, ∑DEHP; fT with MEHHP, MECPP; E2/TT with MiBP; E2/E1 with MEHHP, MECPP. In addition, the significantly negative correlation were found between inhibin B with MnBP, MEHHP, MBzP; P4 with MEHP%; DHEA-S with MEHP%; fT with MBzP, MEHP%; E2/E1 with MEHP% in present study. After adjusting for age, BMI and phlebotomized day, the negative trend between PAE metabolites and some reproductive hormones were found with no significance. The internal estrogenic activities of PAEs in high concentration group were significantly higher than the low concentration group. Finally, the daily intake of PAEs and the hazard index of PAEs were assessed. The daily intake and hazard index of PAEs in high concentration group were significantly higher than those of low concentration group. In conclusions, we found that exposure to PAEs may disrupt the balance of reproductive hormone levels in women, and then affect the reproductive function and menes. However, the actives mechanism of the PAEs exposure on reproductive hormone levels is still unclear in present study. Further researches are needed to collect more data to confirm our findings.
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