Hum. Reprod. Advance Access originally published online on August 3, 2009
Human Reproduction 2009 24(11):2693-2702; doi:10.1093/humrep/dep284
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Factors affecting matrix metalloproteinase-8 levels in the vaginal and cervical fluids in the first and second trimester of pregnancy
1 Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Haartmaninkatu 2, 00029 Helsinki, Finland 2 Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland
3 Correspondence address. E-mail leena.rahkonen{at}hus.fi
BACKGROUND: Cervical ripening during pregnancy resembles an inflammatory process. Matrix metalloproteinases (MMPs), particularly MMP-8, have been linked to inflammatory processes. We studied the concentrations of, and factors associated with, MMP-8 in the lower genital tract fluids in the first and second trimesters.
METHODS: In a prospective population-based cohort study, vaginal and cervical swab samples were obtained from 2130 unselected pregnant women undergoing their first and second trimester ultrasound screening. MMP-8 was determined by immunofluorometric assay. Use of antibiotics, history of vaginal bleeding, and history of sexual intercourse were recorded on both occasions. Vaginal smears were obtained for Gram-staining and leukocyte counting. Cervical length was measured by ultrasonography. The main outcome measures were MMP-8 concentrations in the vagina and cervix.
RESULTS: The median (range) MMP-8 concentrations in vaginal and cervical samples were 107.4 µg/l (undetectable–2406.6 µg/l) and 318.3 µg/l (0.1–2074.6 µg/l), respectively, in the first trimester, and 112.5 µg/l (undetectable–2093.4 µg/l) and 344.8 µg/l (0.4–1783.5 µg/l), respectively, in the second trimester. Multiparity and vaginal leukocytosis were both associated with increased MMP-8 concentrations in vaginal and cervical samples in both trimesters. Bacterial vaginosis (BV) was associated with increased vaginal and cervical MMP-8 in the first trimester, but only with increased vaginal MMP-8 in the second trimester. A history of sexual intercourse (in the previous 48 h) was associated with lower MMP-8 concentrations in cervical samples in both trimesters.
CONCLUSIONS: MMP-8 concentrations were lower in vaginal samples than in cervical samples, and no difference was found between the first and second trimesters. Multiparity, BV and an elevated leukocyte count in the vagina were associated with increased MMP-8 concentrations. Sexual intercourse had an opposite effect. The study suggests that MMP-8 is a physiologic constituent in lower genital tract fluids, where it may be involved in host response to inflammatory and infectious processes.
Key words: matrix metalloproteinase-8/biomarker/pregnancy/lower genital tract
Submitted on April 16, 2009; resubmitted on May 25, 2009; accepted on June 4, 2009.