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Molecular Human Reproduction, Vol. 5, No. 10, 899-907, October 1999
© 1999 European Society of Human Reproduction and Embryology


Molecular endocrinology

Xeno-oestrogens and phyto-oestrogens induce the synthesis of leukaemia inhibitory factor by human and bovine oviduct cells

Karin C. Reinhart1,2, Raghvendra K. Dubey1, Paul J. Keller1, Urs Lauper1 and Marinella Rosselli1,3

1 Department of Obstetrics and Gynaecology, Clinic for Endocrinology, University Hospital, 8091 Zurich, Switzerland and 2 Department of Medicine, Centre for Clinical Pharmacology, University of Pittsburgh Medical Centre, Pittsburgh, PA 15224, USA

Abstract

In bovine oviduct cells 17ß-oestradiol can induce the synthesis of leukaemia inhibitory factor (LIF), a glycoprotein essential for embryo implantation. Therefore substances which are structurally similar to 17ß-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 17ß-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 17ß-oestradiol, genistein (0.02–2 µmol/l) induced LIF synthesis in bovine oviduct cells in a concentration-dependent manner. Equol, biochanin A and daidzein (2 µmol/l), 4-hydroxy-trichlorobiphenyl and 4-hydroxy-dichlorobiphenyl (0.01–10 µmol/l) but not formononetin (2 µmol/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 17ß-oestradiol were blocked by ICI 182,780 (1 µmol/l). Moreover, 17ß-oestradiol, 4-hydroxy-trichlorobiphenyl, 4-hydroxy-dichlorobiphenyl, genistein, tamoxifen and ICI 182,780 displaced [3H]17ß-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.

environmental oestrogens/leukaemia inhibitory factor/17ß-oestradiol/oestrogen receptor/oviduct cells

Notes

3 To whom correspondence should be addressed


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