Endocrine Disrupting Chemicals Exposure and Human Health Outcomes in Different Populations

Ching Chang LeeTaiwan Speaker Endocrine Disrupting Chemicals Exposure and Human Health Outcomes in Different PopulationsUp to now, public concerns about the impact of EDCs on human health is growing steadily. Phthalates are thyroid, reproductive and developmental toxicants. Maternal hypothyroidism during pregnancy can cause adverse effects in the fetus. Study 1 investigates the association between phthalate exposure and thyroid hormones in pregnant women. After adjusting for age, BMI and gestation, urinary MBP levels showed negative associations with FT4 and T4 (FT4:  = -0.110, P < 0.001; T4:  = -0.112, P = 0.003). Exposure to di-n-butyl phthalate (DBP) may affect thyroid activity in pregnant women. Study 2 evaluates the association between maternal urine excretion, the exposure of fetus to phthalates in amniotic fluid, and the health of newborns. We found a significant positive correlation between creatinine adjusted urinary MBP and amniotic fluid MBP (R2=0.156, P <0.05) in all infants and, only in female infants, a significantly negative correlation between amniotic fluid MBP, AGD (R = −0.31, P <0.06), and the anogenital index adjusted by birth weight (AGI-W) (R = −0.32, P <0.05). Our data clearly show that in utero exposure to phthalates in general has anti-androgenic effects on the fetus. Study 3 investigates the association between exposure to phthalates and female puberty, and assesses the effect of leuprorelin acetate treatment on kisspeptin-54 secretion in girls with CPP. All seven urinary phthalate metabolites in the CPP group were significantly higher than in prepubescent controls. Serum kisspeptin-54 level were higher (P = 0.022) in the CPP group than control group and still significantly higher after adjusting for age (P = 0.03). There was a significant increasing trend (Ptrend = 0.005) between levels of kisspeptin and the stages of puberty. Significantly positive correlation between kisspeptin-54 and urinary MBP (R2 = 0.109, P = 0.024) was found. Study 4 explores the biomarkers of altered testicular function associated with exposure to phthalates: the testosterone and INSL3 secretion of adult men with different fertility states. In multiple regression models controlled for potential confounders, there is an inverse association between urinary levels of MMP), mono-iso-butyl phthalate (MiBP), MEHP, MEHP% and serum TT (P = 0.001, 0.007, 0.042 and 0.012). The inverse associations were also found between urinary levels of MiBP, MBzP, MEHP, MEHP% and serum fT (P = 0.028, 0.017, 0.045 and 0.027). Urinary MBzP and MEHP% were negatively associated with a decrease in serum INSL3 (P = 0.049 and 0.001). We also observed a strong inverse relationship between MEHP% quartiles and serum TT, fT, the TT : LH ratio and INSL3 (Ptrend = 0.003, 0.080, 0.002 and 0.012). Serum INSL3, TT, fT and the TT : LH ratio were lower for men in the highest MEHP% quartile than in the reference group (P = 0.007, 0.002, 0.090 and 0.001). In conclusion, the present study showed that infertile men had poor Leydig cell functionality, higher levels of urinary phthalate metabolites and lower concentrations of androgens or INSL3, or both, which implied that being exposed to phthalates might affect human testicular steroidogenesis by impairing the function of Leydig cells. Study 5 investigated the active mechanisms of how being exposed to phthalates affects the imbalance of androgen and estrogen and the generation of ROS to determine whether both mediated phthalate-induced effects are involved in prostatic enlargement. DEHP metabolite levels, particularly urinary MEHP, were positively associated with androgen, estrogen, hormone ratios, inducible nitric oxide synthetase (iNOS), 8-OHdG, prostate specific antigen (PSA), and prostate volume (PV) (P < 0.05). PV and PSA were positively associated with androgen, estrogen, hormone ratios and oxidative stress markers (P < 0.05). The estimated percentages of exposure to phthalates in prostatic enlargement mediated by androgen, estrogen, and OS markers ranged from 3.5% to 63.1%. Exposure to DEHP promoted the progress of BPH by increasing dihydrotestosterone (DHT), estradiol (E2), the converted enzymes aromatase and 5 reductase, and reactive oxygen species (8-OHdG and iNOS) production. Sex hormones and OS might be important hyperplasia-promoters after a patient has been exposed to phthalates, especially to DEHP.