Intrafollicular expression of matrix metalloproteinases and their inhibitors in normally ovulating women compared with patients undergoing in vitro fertilization treatment

D’Ascenzo, Sandra; Giusti, Ilaria; Millimaggi, Danilo; Marci, Roberto; Tatone, Carla; Colonna, Rosella; Mangino, Massimo; Pavan, Antonio; Dolo, Vincenza; Caserta, Donatella

doi:10.1530/eje.0.1510087

Cited by 24 publications

(23 citation statements)

References 15 publications

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“…This finding is consistent with the results of previous animal studies, showing that TIMP-2 mRNA expression was not changed during ovulation in the rat , mouse (Inderdeo et al, 1996) or cow (Smith et al, 1995). Moreover, a comparative study of follicular fluids from IVF cycles and normal menstrual cycles showed no difference in TIMP-2 protein levels between the two groups (D'Ascenzo et al, 2004).…”

Section: Discussionsupporting

confidence: 92%

“…This is now recognized as being due to the activity of MMP-2 and MMP-9. A recent study found that the concentration of MMP-2 and MMP-9 protein in human follicular fluid of natural and IVF cycles was similar during the pre-ovulatory stage of natural cycle and IVF cycles (D'Ascenzo et al, 2004). On the contrary, studies in the rat have demonstrated that the highest expressions of these tissue-remodelling enzymes were in the theca and the surrounding stroma (Reich et al, 1991;Curry et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, an increase of TIMP-1 mRNA was seen after hCG in the rat (Chun et al, 1992;Curry et al, 2000), mouse (Hagglund et al, 1999) and rhesus monkey (Chaffin and Stouffer, 1999) as well as after the mid-cycle gonadotrophin surge in the sheep (Smith et al, 1994). Previous studies on TIMP-1 in the human ovary have been exclusively on cells and follicular fluids obtained from IVF cycles with the apparent disadvantages of using these cells and fluids of hyperstimulated luteinized follicles to study natural ovulation (Shalev et al, 2001;D'Ascenzo et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

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

Lind

Dahm‐Kähler

Weijdegård

et al. 2006

Molecular Human Reproduction

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Lind

Dahm‐Kähler

Weijdegård

et al. 2006

Molecular Human Reproduction

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“…Abdallah et al [25] reported similar follicular fluid levels of MMPs in patients following a clomiphene citrate cycle and patients undergoing IVF treatment with recombinant stimulating hormone. D'ascenzo et al [26] found lower levels of MMP-2 and MMP-9 in the follicular fluid of IVF patients compared to women with normal ovulation, and suggested that gelatinase levels are influenced by the steroidogenesis induced by the gonadotropin protocol for IVF treatment. This study was the first to compare the follicular fluid levels of MMPs using different drug protocols.…”

Section: Discussionmentioning

confidence: 99%

Do follicular fluid gelatinase levels affect fertilization rates and oocyte quality?

Bilen

Tola

Oral

et al. 2014

Arch Gynecol Obstet

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“…Thus, we sought to investigate the possible link between MMPs and the down-regulation of N-cadherin in human OSE. To do so, we first examined the expression of MMP-2 and MMP-9, which have been identified in follicular fluid during follicle growth and ovulation (33,34) in OSE. As shown in Fig.…”

Section: Inhibitor Of Matrix Metalloproteinase Inhibits the Camp-medimentioning

confidence: 99%

Gonadotropins Regulate N-cadherin-mediated Human Ovarian Surface Epithelial Cell Survival at Both Post-translational and Transcriptional Levels through a Cyclic AMP/Protein Kinase A Pathway

Pon

Auersperg

Wong

2005

Journal of Biological Chemistry

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Gonadotropins are the major regulators of ovarian function and may be involved in the etiology of ovarian cancer. In this study, we report a new mechanism whereby gonadotropins regulate the survival of human ovarian surface epithelium (OSE), the tissue of origin of epithelial ovarian carcinomas. Our results indicate that disruption of N-cadherin-mediated cell-cell adhesion is an important molecular event in the apoptosis of human OSE. Treatment with surge serum concentrations of gonadotropins reduced the amount of N-cadherin with a concomitant induction of apoptosis, and this effect was mediated by a cAMP/protein kinase A pathway but not the ERK1/2 and protein kinase C cascades. We further demonstrated that activation of the gonadotropins/ cAMP signaling pathway in human OSE led to a rapid down-regulation of N-cadherin protein level followed by a reduction at the level of N-cadherin mRNA, indicating that expression of N-cadherin was regulated by posttranslational and transcriptional mechanisms. The former mechanism was mediated by increased turnover of N-cadherin protein and could be reversed by inhibition of proteasomal or matrix metalloproteinase (MMP-2) activity. On the other hand, at the transcriptional level, the addition of actinomycin D abolished the cAMP-mediated decrease in N-cadherin mRNA but did not change its stability. Inhibition of protein kinase A or expressing a dominant negative mutant of cAMP-response elementbinding protein blocked this decrease of N-cadherin mRNA. Together, the combined operation of post-translational and transcriptional mechanisms suggests that regulation of N-cadherin is a crucial event and emphasizes the important role that N-cadherin has in controlling the survival capability of human OSE.The surface of the human ovary is covered with a single layer of flat-to-cuboidal mesothelial cells, the ovarian surface epithelium (OSE).1 During each reproductive cycle, the OSE takes part in the cyclical ovulatory ruptures and repair. OSE on the preovulatory follicle undergoes apoptosis at the time of ovulation and then proliferates rapidly to repair the ruptured follicle and reconstitutes an intact mesothelium (1). However, factors regulating cell death and growth in human OSE are poorly understood. Because OSE is the source of epithelial ovarian carcinomas, which is the leading cause of death among all the human gynecological neoplasms, understanding the mechanisms that regulate OSE cell survival, apoptosis, and cell growth is of great clinical importance because an aberrant signaling of any of these pathways is likely to be involved in epithelial ovarian cancer. The cadherins are a family of cell surface glycoproteins that function in promoting calcium-dependent cell-cell adhesion and play crucial roles in the maintenance of structure, differentiation, and function of reproductive tissues (reviewed in Ref. 2). In general, cadherins are expressed in a cell-specific manner within specific compartments of the ovary, and their expression shows changes during different differentiation or...

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Intrafollicular expression of matrix metalloproteinases and their inhibitors in normally ovulating women compared with patients undergoing in vitro fertilization treatment

Cited by 24 publications

References 15 publications

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

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

Do follicular fluid gelatinase levels affect fertilization rates and oocyte quality?

Gonadotropins Regulate N-cadherin-mediated Human Ovarian Surface Epithelial Cell Survival at Both Post-translational and Transcriptional Levels through a Cyclic AMP/Protein Kinase A Pathway

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