Endometriosis May Be Promoted by Midkine: Possible Involvement of Ovarian Follicles
Abstract
Endometriosis is an enigmatic disease, the etiology of which is poorly understood. The lesion of endometriosis is preferentially located in the peritoneum around the ovary. We therefore speculated that some local factor derived from the ovary is involved in the development of endometriosis. Relatively high concentrations (higher than 200 ng/ml) of midkine are detected in follicular fluids in the ovary, implying its roles in the follicular growth. In contrast, concentrations of midkine in peritoneal fluid are around 1 ng/ml. Midkine concentrations in peritoneal fluid increase after ovulation, suggesting that midkine in follicular fluid erupting at ovulation contribute to the concentrations in peritoneal fluid. Interestingly, midkine (higher than 100 ng/ml) stimulates the proliferation of endometriotic stromal cells. Therefore, it is plausible that endometriotic lesions are stimulated to grow by directly exposed to midkine in follicular fluid at the time of ovulation. In addition, midkine concentrations in peritoneal fluid are higher in women with advanced endometriosis compared to those with no or minimal endometriosis, further suggesting the involvement of MK in endometriosis.
Keywords
Endometriosis Ovulation Follicular fluid Peritoneal fluid MidkineNotes
References
- 1.Muramatsu T (2010) Midkine, a heparin-binding cytokine with multiple roles in development, repair and diseases. Proc Jpn Acad Ser B Phys Biol Sci 86:410–425PubMedCrossRefGoogle Scholar
- 2.Chung HW, Wen Y, Choi EA et al (2002) Pleiotrophin (PTN) and midkine (MK) mRNA expression in eutopic and ectopic endometrium in advanced stage endometriosis. Mol Hum Reprod 8:350–355PubMedCrossRefGoogle Scholar
- 3.Giudice LC (2010) Endometriosis. N Engl J Med 362:2389–2398PubMedCrossRefGoogle Scholar
- 4.Osuga Y (2008) Novel therapeutic strategies for endometriosis: a pathophysiological perspective. Gynecol Obstet Invest 66(Suppl 1):3–9PubMedCrossRefGoogle Scholar
- 5.Osuga Y, Koga K, Hirota Y et al (2010) Lymphocytes in endometriosis. Am J Reprod Immunol 65:1–10CrossRefGoogle Scholar
- 6.Ohyama Y, Miyamoto K, Minamino N et al (1994) Isolation and identification of midkine and pleiotrophin in bovine follicular fluid. Mol Cell Endocrinol 105:203–208PubMedCrossRefGoogle Scholar
- 7.Karino S, Minegishi T, Ohyama Y et al (1995) Regulation and localization of midkine in rat ovary. FEBS Lett 362:147–150PubMedCrossRefGoogle Scholar
- 8.Minegishi T, Karino S, Tano M et al (1996) Regulation of midkine messenger ribonucleic acid levels in cultured rat granulosa cells. Biochem Biophys Res Commun 229:799–805PubMedCrossRefGoogle Scholar
- 9.Hirota Y, Osuga Y, Nose E et al (2007) The presence of midkine and its possible implication in human ovarian follicles. Am J Reprod Immunol 58:367–373PubMedCrossRefGoogle Scholar
- 10.Hirota Y, Osuga Y, Koga K et al (2005) Possible implication of midkine in the development of endometriosis. Hum Reprod 20:1084–1089PubMedCrossRefGoogle Scholar
- 11.Arimoto T, Katagiri T, Oda K et al (2003) Genome-wide cDNA microarray analysis of gene-expression profiles involved in ovarian endometriosis. Int J Oncol 22:551–560PubMedGoogle Scholar
- 12.Inoh K, Muramatsu H, Ochiai K et al (2004) Midkine, a heparin-binding cytokine, plays key roles in intraperitoneal adhesions. Biochem Biophys Res Commun 317:108–113PubMedCrossRefGoogle Scholar
- 13.Bahtiyar MO, Seli E, Oral E et al (1998) Follicular fluid of women with endometriosis stimulates the proliferation of endometrial stromal cells. Hum Reprod 13:3492–3495PubMedCrossRefGoogle Scholar
- 14.Frederick JL, Shimanuki T, diZerega GS (1984) Initiation of angiogenesis by human follicular fluid. Science 224:389–390PubMedCrossRefGoogle Scholar