title: 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-alpha (ER-alpha) expression in the newborn mouse uterine epithelium after prenatal exposure. Pregnant mice were given daily s.c. injections with DES (10 or 100 microgram 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-alpha expression was evaluated on histological sections by detecting ER-alpha mRNA with the in situ hybridization technique and ER-alpha 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-alpha mRNA or protein, while both were highly expressed in the stroma. Exposure to either DES dose induced the expression of both ER-alpha mRNA and protein in the epithelium, whereas it was unchanged in the stroma. In contrast, neither OP dose induced the expression of ER-alpha 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.
authors.affiliation: Department of Clinical Studies, Reproduction, The Royal Veterinary and Agricultural University, Copenhagen, Denmark. majken.lrb@rh.dk
authors.forename: M
authors.initials: M
authors.lastname: Nielsen
authors.forename: P E
authors.initials: PE
authors.lastname: Høyer
authors.forename: J G
authors.initials: JG
authors.lastname: Lemmen
authors.forename: B
authors.initials: B
authors.lastname: van der Burg
authors.forename: A G
authors.initials: AG
authors.lastname: Byskov
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004848:Epithelium / Q000378:metabolism; D047628:Estrogen Receptor alpha; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D051379:Mice; D010636:Phenols / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013501:Surface-Active Agents / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D010636:Phenols; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013501:Surface-Active Agents; D004054:Diethylstilbestrol; C105260:4-tert-octylphenol