title: Anti-estrogen prevents xenoestrogen-induced testicular pathology of eelpout (Zoarces viviparus).
abstract: Estrogenic alkylphenols have been shown to affect the reproductive system of male fish causing induction of vitellogenin synthesis and altered testis structure. However, it is still unknown whether the histopathological effects on the testes is mediated by the estrogen receptor or if it represent general toxicopathological effects. In the present study, the effects of different concentrations of the estrogenic chemical 4-tert-octylphenol on vitellogenin (Vtg) synthesis and testicular structure were investigated in the eelpout Zoarces viviparus during spermatogenesis. Adult male eelpout were exposed to 4-tOP (nominal concentrations: 10, 50 or 100 microg l(-1)) or 17beta-estradiol (E2; 0.5 microg l(-1)) in a continuous flow-through system for 3 weeks. A group of fish were exposed to 4-tOP (50 microg l(-1)) concomitantly with the anti-estrogen ZM 189,154 (20 microg g(-1) week(-1), i.p.). The Vtg concentration in plasma was measured by enzyme-linked immunosorbent assay. The testicular structure was examined by light microscopy and gamma-glutamyl transpeptidase (gamma-GTP) activity was measured in the testes. The testicular localization of gamma-GTP was analysed by enzyme histochemistry. A marked increase in the plasma Vtg concentration was observed after exposure to the actual concentration of 35 microg l(-1) 4-tOP (nominal concentration, 50 microg l(-1)), 63 microg l(-1) 4-tOP (nominal concentration, 100 microg l(-1)) or E2. Co-treatment with ZM 189,154 totally abolished the 4-tOP-dependent induction of Vtg synthesis. Exposure to 4-tOP or E2 caused a marked reduction in the testis mass and severely affected the testicular development and structure including the Sertoli cells (based on histology and gamma-GTP activity), resulting in impairment of spermatogenesis and degeneration of lobular structures. Other cellular abnormalities such as accumulations of yellowish-brown pigmented cells and increased interstitial fibrosis in the testes was also observed in the exposed fish. In the groups exposed to the nominal concentrations of 50 or 100 microg l(-1) all fish had severely affected testes, while both normal, moderately and severely affected testes were found in the group exposed to the nominal concentration of 10 microg l(-1). Co-treatment with ZM 189,154 abolished part of these 4-tOP-induced effects on the testicular growth and histological structure. The study demonstrates that an anti-estrogen can abolish effects on the testis caused by estrogenic chemicals, providing evidence that some of the effects are mediated by the estrogen receptor.
authors.affiliation: Institute of Biology, University of Southern Denmark, Odense, Campusvej 55, DK-5230 Odense M, Denmark. tinac@biology.sdu.dk
authors.forename: Tina H
authors.initials: TH
authors.lastname: Rasmussen
authors.forename: Swee J
authors.initials: SJ
authors.lastname: Teh
authors.forename: Poul
authors.initials: P
authors.lastname: Bjerregaard
authors.forename: Bodil
authors.initials: B
authors.lastname: Korsgaard
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006651:Histocytochemistry; D006652:Histological Techniques; D008297:Male; D009659:North Sea; D010473:Perciformes / Q000378:metabolism*; D010636:Phenols / Q000037:antagonists & inhibitors / Q000633:toxicity*; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014818:Vitellogenesis / Q000187:drug effects*; D005723:gamma-Glutamyltransferase / Q000378:metabolism; D005466:Fluorocarbons
chemical_list: D010636:Phenols; D013764:Tetrahydronaphthalenes; D005723:gamma-Glutamyltransferase; C088608:ZM 189154; D005466:Fluorocarbons; C105260:4-tert-octylphenol