Gelatinases and their tissue inhibitors during human ovulation: increased expression of tissue inhibitor of matrix metalloproteinase-1

• Published in: Molecular human reproduction 2006-12, Vol.12 (12), p.725-736
• Main Authors: Lind, A.-K., Dahm-Kähler, P., Weijdegård, B., Sundfeldt and, K., Brännström, M.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Blotting, Western; Chorionic Gonadotropin - pharmacology; Embryology: invertebrates and vertebrates. Teratology; Enzyme Induction; Extracellular Matrix - metabolism; Female; follicle; Fundamental and applied biological sciences. Psychology; Granulosa Cells - metabolism; human; Humans; Immunoenzyme Techniques; Matrix Metalloproteinase 2 - physiology; Matrix Metalloproteinase 9 - physiology; MMP; Ovarian Follicle - metabolism; ovary; ovulation; Ovulation - physiology; Ovulation Induction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Stromal Cells - metabolism; Theca Cells - metabolism; TIMP; Tissue Inhibitor of Metalloproteinase-1 - biosynthesis; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-1 - physiology; Tissue Inhibitor of Metalloproteinase-2 - physiology
• ISSN: 1360-9947; 1460-2407
• DOI: 10.1093/molehr/gal086

Remodelling of the extracellular matrix (ECM) of the follicular wall by matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) has been suggested to be crucial in ovulation. To investigate the expression of the gelatinases, MMP-2 and MMP-9, together with their inhibitors, TIMP-2 and TIMP-1, in the perifollicular ovarian stroma from women just before and during ovulation, we obtained biopsies of the stroma adjacent to the leading follicle. Laparoscopic surgery was performed either before the LH peak or at any of three intervals after ovulation triggering by hCG. Immunoblotting, immunohistochemistry and quantitative RT–PCR were performed. All four proteins were expressed by immunoblots, with no detectable changes in the expression of MMP-2, MMP-9 and TIMP-2. Scattered immunostaining for MMP-9 and TIMP-2 was seen, and MMP-2 was demonstrated in a concentric layer. A significant increase in TIMP-1 protein and mRNA was seen during the three ovulatory phases, and a strong and patchy immunostaining for TIMP-1 was shown. This is the first study that has demonstrated an ovulation-associated expression of these ECM-remodelling enzymes around the human follicle at ovulation. The increased expression of TIMP-1 may reflect a specific temporal inhibition of collagenolysis and thereby a time-dependent regulation of ECM breakdown in areas surrounding the apex of the follicle.