Octylphenol does not mimic diethylstilbestrol-induced oestrogen receptor-alpha expression in the newborn mouse uterine epithelium after prenatal exposure.
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.
Nielsen
M
M
Department of Clinical Studies, Reproduction, The Royal Veterinary and Agricultural University, Copenhagen, Denmark. majken.lrb@rh.dk
Høyer
P E
PE
Lemmen
J G
JG
van der Burg
B
B
Byskov
A G
AG
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
D047628:Estrogen Receptor alpha; D010636:Phenols; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013501:Surface-Active Agents; D004054:Diethylstilbestrol; C105260:4-tert-octylphenol