title: Xeno-oestrogens and phyto-oestrogens induce the synthesis of leukaemia inhibitory factor by human and bovine oviduct cells.
abstract: In bovine oviduct cells 17beta-oestradiol can induce the synthesis of leukaemia inhibitory factor (LIF), a glycoprotein essential for embryo implantation. Therefore substances which are structurally similar to 17beta-oestradiol and possess oestrogenic activity may also modulate LIF synthesis and influence the reproductive process. We used primary cultures of bovine and human oviduct cells (epithelial cells:fibroblasts 1:1) to compare the effects of 17beta-oestradiol, phyto-oestrogens (genistein, biochanin A, daidzein, formononetin, and equol) and xeno-oestrogens [polychlorinated biphenyls (PCB): trichlorobiphenyl, 4-hydroxy-trichlorobiphenyl and 4-hydroxy-dichlorobiphenyl] on LIF synthesis. Immunoreactive LIF-enzyme-linked immunosorbent assay was used to determine the concentration of LIF in the culture medium. Similar to 17beta-oestradiol, genistein (0.02-2 micromol/l) induced LIF synthesis in bovine oviduct cells in a concentration-dependent manner. Equol, biochanin A and daidzein (2 micromol/l), 4-hydroxy-trichlorobiphenyl and 4-hydroxy-dichlorobiphenyl (0.01-10 micromol/l) but not formononetin (2 micromol/l) also induced LIF synthesis in bovine cells. Phyto-oestrogens and xeno-oestrogens also induced LIF synthesis in human oviduct cells (P < 0.05). The stimulatory effects of PCB, phyto-oestrogens and 17beta-oestradiol were blocked by ICI 182,780 (1 micromol/l). Moreover, 17beta-oestradiol, 4-hydroxy-trichlorobiphenyl, 4-hydroxy-dichlorobiphenyl, genistein, tamoxifen and ICI 182,780 displaced [(3)H]17beta-oestradiol from cytosolic oestrogen receptors in bovine oviduct cells. These results suggest that phyto-oestrogens and PCB mimic the effects of oestradiol in inducing LIF synthesis by bovine and human oviduct cells and that these stimulatory effects are oestrogen receptor-mediated. Environmental oestrogens act as endocrine modulators/disrupters and may induce deleterious effects on the reproductive process by influencing LIF synthesis in a non-cyclic fashion leading to tubal infertility.
authors.affiliation: Department of Obstetrics and Gynaecology, Clinic for Endocrinology, University Hospital, 8091 Zurich, Switzerland.
authors.forename: K C
authors.initials: KC
authors.lastname: Reinhart
authors.forename: R K
authors.initials: RK
authors.lastname: Dubey
authors.forename: P J
authors.initials: PJ
authors.lastname: Keller
authors.forename: U
authors.initials: U
authors.lastname: Lauper
authors.forename: M
authors.initials: M
authors.lastname: Rosselli
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005187:Fallopian Tubes / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D000077267:Fulvestrant; D019833:Genistein / Q000633:toxicity; D006131:Growth Inhibitors / Q000096:biosynthesis*; D006801:Humans; D007247:Infertility, Female / Q000209:etiology; D015850:Interleukin-6; D007529:Isoflavones; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis*; D048789:Phytoestrogens; D028321:Plant Preparations; D011078:Polychlorinated Biphenyls / Q000633:toxicity
chemical_list: D004965:Estrogen Antagonists; D004968:Estrogens, Non-Steroidal; D006131:Growth Inhibitors; D015850:Interleukin-6; D007529:Isoflavones; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D048789:Phytoestrogens; D028321:Plant Preparations; C105195:4-hydroxy-2',4',6'-trichlorobiphenyl; D000077267:Fulvestrant; D004958:Estradiol; D011078:Polychlorinated Biphenyls; D019833:Genistein