Octylphenol does not mimic diethylstilbestrol-induced oestrogen receptor-alpha expression in the newborn mouse uterine epithelium after prenatal exposure

Abstract

This study examined whether the endocrine disruptor octylphenol (OP) mimics the synthetic oestrogen diethylstilbestrol (DES) in ability to induce oestrogen receptor-(ER-) expression in the newborn mouse uterine epithelium after prenatal exposure. Pregnant mice were given daily s.c. injections with DES (10 or 100 µg DES/kg maternal wt) or OP (100 or 250 mg/kg maternal wt) or with vehicle alone from day 11·5 to 16·5 of pregnancy. ER-expression was evaluated on histological sections by detecting ER-mRNA with the in situ hybridization technique and ER-protein using immunohistochemistry. The immunostaining was quantitated using a microspectrophotometer. Oestrogen-like activity of the DES and OP batches used for in vivo exposure was confirmed in an in vitro assay based on transient gene expression of an oestrogen-dependent reporter plasmid. In mice exposed prenatally to vehicle alone, the uterine epithelium did not express either ER-mRNA or protein, while both were highly expressed in the stroma. Exposure to either DES dose induced the expression of both ER-mRNA and protein in the epithelium, whereas it was unchanged in the stroma. In contrast, neither OP dose induced the expression of ER-mRNA or protein in the epithelium and expression was unchanged in the stroma. Our data stress the importance of in vivo studies when investigating endocrine disruptors.

The Biomarker and Endocrine Disruptors in Mammals

“…Exposure to DES induced the expression of both ERα mRNA and protein in the epithelium, whereas it was unchanged in the stroma. In contrast, OP did not induce the expression of ERα mRNA or protein in the epithelium and the expression was unchanged in the stroma, suggesting the importance of in vivo studies in the detection of EDs [24]. I n t h e m ale m o us e, s elec t ed m o no c lo n al antibodies against intra-acrosomal mammalian sp e r m pr ote i ns c r oss -r e ac ted w i th m o u se spermatozoa, which were analyzed for acrosome integrity to detect EDs [25].…”

“…It is generally acknowledged that (1) total metabolizable energy in natural ingredients or purified diets has a significant effect on the uterine w e i g h ts o f i m m at u r e m i c e u se d i n 7-d a y uterotro phic bioas sa ys ; (2) a sta ndard iz ed , es tr og en-free d iet w it h a co ns t ant level o f m et abo lizable energy needs t o be used for conducting uterotrophic assays when comparing results between different laboratories or when determining the estrogenic or anti-estrogenic activity of EDs; (3) the mouse uterotrophic assay is a sensitive bioassay for assessing chemicals for estrogenic activity or for the detection of total estrogenic activity in rodent diets that may be contaminated with estrogenic compounds; and (4) chemical assays need to be used to detect or measure low levels of phytoestrogens in rodent diets [23]. The effect of OP has been investigated and compared with that of DES in ability to induce ERα expression in the newborn mouse uterine epithelium after prenatal exposure [24]. Exposure to DES induced the expression of both ERα mRNA and protein in the epithelium, whereas it was unchanged in the stroma.…”

Expression profiling of estrogen responsive genes on bisphenol A, 4-nonylphenol and 17β-estradiol treatment using in house cDNA microarray

“…The need for advancing prediction the adverse biological effects of EDCs in mammalian has made technologies exploiting advances in molecular techniques. Current molecular-level techniques rely on ligand-binding assays 18 , enzyme-linked immunosorbent assay (ELISA) 19 , and more recently, gene expression profiling [20][21][22][23] . In the near future, more reliance will be placed on the development of gene expression assays to determine the intricate interactions between genes that are affected by the exposures.…”

Maternal Exposure to Bisphenol A during Late Pregnancy Resulted in an Increase of Calbindin-D9k mRNA and Protein in Maternal and Postnatal Rat Uteri

“…DES was rapidly absorbed and distributed to maternal mouse organs. It accumulated in the liver and was rapidly distributed to the fetus where it induced ERα expression in the newborn mouse uterine epithelium [19,20]. BPA appeared to be transferred r a p i d l y a c r o s s t h e p l a c e n t a , m u c h l i k e thiabendazole, and salicylic acid, and its maximal fetal concentration was 30-100% of its maximal maternal plasma level [21,22].…”