Human Reproduction, Vol. 14, No. 3, 807-815,
March 1999
© 1999 European Society of Human Reproduction and Embryology
Endometrial breakdown in women using Norplant is associated with migratory cells expressing matrix metalloproteinase-9 (gelatinase B)*
1 Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Victoria 3168, Australia, 2 Monash University Dept. of Obstetrics and Gynaecology, Clayton, Victoria 3168, Australia and 3 Human Reproduction Study Group, Department of Obstetrics and Gynaecology, University of Indonesia, Klinik Raden Salah, Jalan Raden Salah 49, Jakarta, 10330, Indonesia
Norplant, subdermally implanted slow-release levonorgestrel, is an effective and widely used contraceptive agent but has a high rate of discontinuation due to unacceptable abnormal uterine bleeding. Matrix metalloproteinases (MMPs) are expressed in normal cycling endometrium and are postulated to be responsible for the tissue breakdown at menstruation. We have compared the immunolocalization of MMP-9 and migratory cells in endometrium from Indonesian women using Norplant with normal controls. Positive MMP-9 immunostaining was observed intracellularly within stromal and intravascular leukocytes and extracellularly in areas of tissue lysis adjacent to these migratory cells. The MMP-9 positive cells were identified as neutrophils, eosinophils, CD3+ T-cells and macrophages. Quantitative assessment revealed that the number of MMP-9 positive cells, neutrophils and eosinophils were significantly increased in those endometrial biopsies from Norplant users displaying a shedding morphology and in normal controls at menstruation. There was no correlation between the number of MMP-9 positive cells and the number of bleeding days reported. Endometrial immunostaining for tissue inhibitor of metalloproteinases was similar in Norplant users and normal controls. These results suggest that MMP-9, an enzyme capable of degrading basement membrane components, may be involved in endometrial breakdown in women using Norplant.
Key words: : endometrial bleeding/immunochemistry/leukocyte/matrix metalloproteinase-9/Norplant
*Parts of this work were presented in abstract form at the 28th Australian Society for Reproductive Biology Meeting, 1997 (abstract 60) and the 45th Society for Gynecological Investigation Meeting, 1998 (abstract 305).
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