Possible implication of midkine in the development of endometriosis

Yasushi Hirota, Osuga Y, Yutaka Osuga, Kaori Koga, Yoshino O, Osamu Yoshino, Tetsuya Hirata, Miyuki Harada, Chieko Morimoto, Morimoto C, Tetsu Yano, Yano T, Osamu Tsutsumi, Tsutsumi O, Sadatoshi Sakuma, Sakuma S, Muramatsu T, Takashi Muramatsu, Yuji Taketani, Taketani Y
Human Reproduction · 2005 · vol. 20(4) , pp. 1084–1089 · doi:10.1093/humrep/deh720 · PMID:15734764 · W2142195365
article OA: bronze CC0 ⤵ 26 in-corpus citations
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Midkine (MK) increased endometriotic stromal cell proliferation in vitro, and higher MK concentrations in peritoneal fluid correlated with advanced endometriosis and specific menstrual phases.

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Abstract

BACKGROUND: The present study was conducted to assess whether midkine (MK), a multifunctional molecule known to stimulate tumor growth, may be involved in the development of endometriosis. METHODS: The mitogenic activity of MK on cultured endometriotic stromal cells was examined by measuring 5-bromo-2'-deoxyuridine (BrdU) incorporation. Concentrations of MK in the peritoneal fluid (PF) of women without or with endometriosis and those under GnRH agonist treatment were measured using a specific enzyme immunoassay. The expression of MK mRNA in peritoneal bone marrow-derived cells, peritoneum and endometriotic tissues was evaluated by RT-PCR. RESULTS: MK significantly increased BrdU incorporation into the DNA of cultured endometriotic stromal cells. The MK concentrations in the PF of the women with advanced endometriosis (stages II, III and IV) Median: 1.21 ng/ml; interquartile range 0.80-2.27 were significantly higher than those of the women without endometriosis and with stage I endometriosis (0.06 ng/ml, 0.67-1.26, P < 0.05). As for the menstrual phase, the MK concentration in PF in the inteal phase (1.32 ng/ml. 0.72-2.21) were significantly higher than those in the follicular phase (0.95 ng/ml, 0.68-1.24, P < 0.05). In addition, women with adnexal adhesions had higher concentrations of MK in PF than those without adhesions (P < 0.05). The MK concentrations of the women under GnRH agonist treatment were significantly lower than those of the other groups (P < 0.001). The expression of MK mRNA was detected in peritoneal bone marrow-derived cells, peritoneum and endometriotic tissues. CONCLUSIONS: The present findings suggest that MK may play roles, such as stimulation of endometriotic cell proliferation, in the development of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Cytokines Cytokines Endometriosis Endometriosis Adult Ascitic Fluid Ascitic Fluid Cell Division Cell Division Cytokines Endometriosis Endometriosis Endometrium Endometrium Endometrium Female Follicular Phase Follicular Phase Humans Middle Aged

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