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ORIGINAL RESEARCH ARTICLE

Phytoestrogens Modulate Prostaglandin Production in Bovine Endometrium: Cell Type Specificity and Intracellular Mechanisms

Izabela Woclawek-Potocka^*, Tomas J. Acosta, Anna Korzekwa^*, Mamadou M. Bah^*, Masami Shibaya, Kiyoshi Okuda and Dariusz J. Skarzynski^*,1

^* Department of Reproductive Immunology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland; and Laboratory of Reproductive Endocrinology, Faculty of Agriculture, Okayama University, Okayama 700-8530, Japan

To whom requests for reprints should be addressed at ¹ Laboratory of Reproductive Endocrinology, Faculty of Agriculture, Okayama University, Okayama 700-8530, Japan. E-mail: skadar{at}pan.olsztyn.pl

Prostaglandins (PGs) are known to modulate the proper cyclicity of bovine reproductive organs. The main luteolytic agent in ruminants is PGF₂, whereas PGE₂ has luteotropic actions. Estradiol 17ß (E₂) regulates uterus function by influencing PG synthesis. Phytoestrogens structurally resemble E₂ and possess estrogenic activity; therefore, they may mimic the effects of E₂ on PG synthesis and influence the reproductive system. Using a cell-culture system of bovine epithelial and stromal cells, we determined cell-specific effects of phytoestrogens (i.e., daidzein, genistein), their metabolites (i.e., equol and para-ethyl-phenol, respectively), and E₂ on PGF₂ and PGE₂ synthesis and examined the intracellular mechanisms of their actions. Both PGs produced by stromal and epithelial cells were significantly stimulated by phytoestrogens and their metabolites. However, PGF₂ synthesis by both kinds of cells was greater stimulated than PGE₂ synthesis. Moreover, epithelial cells treated with phytoestrogens synthesized more PGF₂ than stromal cells, increasing the PGF₂ to PGE₂ ratio. The epithelial and stromal cells were preincubated with an estrogen-receptor (ER) antagonist (i.e., ICI), a translation inhibitor (i.e., actinomycin D), a protein kinase A inhibitor (i.e., staurosporin), and a phospholipase C inhibitor (i.e., U73122) for 0.5 hrs and then stimulated with equol, para-ethyl-phenol, or E₂. Although the action of E₂ on PGF₂ synthesis was blocked by all reagents, the stimulatory effect of phytoestrogens was blocked only by ICI and actinomycin D in both cell types. Moreover, in contrast to E₂ action, phytoestrogens did not cause intracellular calcium mobilization in either epithelial or stromal cells. Phytoestrogens stimulate both PGF₂ and PGE₂ in both cell types of bovine endometrium via an ER-dependent genomic pathway. However, because phytoestrogens preferentially stimulated PGF₂ synthesis in epithelial cells of bovine endometrium, they may disrupt uterus function by altering the PGF₂ to PGE₂ ratio.

Key Words: cattle • endometrium • phytoestrogens • PGF₂ • PGE₂

This article has been cited by other articles:

				C. Hermenegildo, P. J. Oviedo, M. A. Garcia-Perez, J. J. Tarin, and A. Cano Effects of Phytoestrogens Genistein and Daidzein on Prostacyclin Production by Human Endothelial Cells J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 722 - 728. [Abstract] [Full Text] [PDF]