Expression of erythropoietin in human female reproductive organs

Erythropoietin (Epo) is known to be a lineage specific cytokine which regul ates the number of circulating erythrocytes. Most of it is produced in the kidney. Recently, Epo has been reported to be synthesized in the normal bra in, placenta, and capillary endothelium. We also have found that uterine en dometrium expresses Epo signals in an estrogen-dependent manner, and that E po contributes to angiogenesis in the endometrium in mice. To clarify the f unctional activity of Epo in human reproductive organs, we examined Epo sig naling in these organs by Southern analysis of RT-PCR products and studied the distribution of substances relevant to Epo signal transduction by immun ohistochemistry and Western blotting. Epo mRNA is expressed in the normal h uman cervix, endometrium and ovary, but it is not always detected in the sp ecimens. Immunohistochemical analysis revealed Epo-receptor (EpoR) protein in: a) th e endothelium of vessels, in glandular and surface epithelial cells, in dec idual cells of the endometrium, and b) in follicles at various stages inclu ding oocytes, granulosa, theca interna cells and lutein cells of the ovary. Moreover, co-expression of JAK2 and phosphotyrosine, which reflects tyrosi ne phosphorylation via JAK2, and co-expression of EpoR and STAT5, which is a transcriptional factor relevant to mitogenic activity, were seen at these Epo-responsive sites. Western blotting analysis of these organs confirmed the immunohistochemical results. These findings imply that female reproduct ive organs can produce Epo, and that signal transduction of Epo contributes to the cyclic changes in the female reproductive organs.