Chronic Low-Dose Nonylphenol or Di-(2-ethylhexyl) Phthalate has a Different Estrogen-like Response in Mouse Uterus

Abstract

Through the development of organic synthetic skill, chemicals that mimic signaling mediators such as steroid hormones have been exposed to the environment. Recently, it has become apparent that this circumstance should be further studied in the field of physiology. Estrogenic action of chronic low-dose nonylphenol (NP) and di-(2-ethylhexyl) phthalate (DEHP) in mouse uterus was assessed in this study. Ten to twelve-week-old female mice (CD-1) were fed drinking water con-taining NP (50 or 500 μg/L) or DEHP (133 or 1,330 μg/L) for 10 weeks. Uterine diameter, the thickness of myometrium and endometrium, and the height of luminal epithelial cells were measured and the number of glands were counted. The expres-sion levels of the known 17-estradiol (E2)-regulated genes were evaluated with real-time RT-PCR methodology. The ration of uterine weight to body weight increased in 133 g/L DEHP. Endometrial and myometrial thickness increased in 133 and 1,330 g/L DEHP treated groups, and in 50, 500 g/L NP and 133 g/L DEHP, respectively. The height of luminal epithelial cell decreased in NP groups. The numbers of gland were decreased in NP groups but increased in 50 g/L DEHP group. The histological characters of glands were not much different between groups. The mRNA expression profiles of the known 17β-estradiol (E2) downstream genes were also different between NP and DEHP groups. The expression levels dramatically in-creased in some genes by the NP or DEHP. Based on these results, it is suggested that the chronic low-dose NP or DEHP works as estrogen-like messengers in uterus with their own specific gene expression-regulation patterns.