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Differential elevation of matrix metalloproteinase expression in women exposed to levonorgestrel-releasing intrauterine system for a short or prolonged period of time.
- Source :
-
Human reproduction (Oxford, England) [Hum Reprod] 2009 Jan; Vol. 24 (1), pp. 113-21. Date of Electronic Publication: 2008 Sep 23. - Publication Year :
- 2009
-
Abstract
- Background: The levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective contraceptive and has many non-contraceptive health benefits. However, it is commonly associated with irregular endometrial bleeding. Metalloproteinases contribute to extracellular matrix (ECM) remodelling and regulate bleeding during the menstrual cycle. Enhanced metalloproteinase expression participates in the pathogenesis of breakthrough bleeding. Thus the objective of this study was to compare matrix metalloproteinase (MMP) expression in endometrium during luteal phase and in short-term (1 month) and long-term (> or =6 months) LNG-IUS users.<br />Methods: MMP expression was analysed by semi-quantitative RT-PCR and immunohistochemistry. Gelatinase activity was determined by gelatin zymography.<br />Results: MMP-1, -2, -3, -7, -9 and -12 mRNAs levels were increased, whereas that of MMP-26 was decreased in the endometrium of LNG-IUS users. MMP-1, -2, -3, -7 and -9 were localized by immunohistochemistry in all biopsies in the short-term group but in only 0-27% in the control group. The incidence of positive immunostaining for MMP-2 and -3 decreased significantly in the long-term compared with short-term LNG-IUS users. MMP-26 was localized in all biopsies from the control group but in only 14 and 25% from the short- and long-term LNG-IUS groups, respectively. In both LNG groups, the numbers of macrophages (the major source of MMP-12) was increased.<br />Conclusions: MMP-1, active MMP-2, MMP-3, MMP-7, MMP-9 and MMP-12 are more prevalent in the short-term LNG-IUS group, suggesting their important contribution to ECM breakdown and transient bleeding. The decrease in the percentage of women expressing MMP-2 and -3 might contribute to the decreased occurrence of unwanted spotting and bleeding in long-term LNG-IUS users.
- Subjects :
- Adult
Contraceptive Agents, Female pharmacology
Endometrium cytology
Endometrium metabolism
Female
Gelatinases metabolism
Gene Expression Regulation drug effects
Humans
Immunohistochemistry
Levonorgestrel pharmacology
Luteal Phase metabolism
Macrophages cytology
Macrophages drug effects
Matrix Metalloproteinase 2 genetics
Matrix Metalloproteinase 2 metabolism
Matrix Metalloproteinase 9 genetics
Matrix Metalloproteinase 9 metabolism
Matrix Metalloproteinases genetics
Middle Aged
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Contraceptive Agents, Female administration & dosage
Endometrium drug effects
Intrauterine Devices, Medicated
Levonorgestrel administration & dosage
Luteal Phase drug effects
Matrix Metalloproteinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2350
- Volume :
- 24
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Human reproduction (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 18812421
- Full Text :
- https://doi.org/10.1093/humrep/den339