Decreased expression of tissue inhibitor of matrix metalloproteinases in follicular fluid from women with polycystic ovaries compared with normally ovulating patients undergoing in vitro fertilization

Lahav-Baratz, Shirly; Kraiem, Zaki; Shiloh, Hanna; Koifman, Mara; Ishai, David; Dirnfeld, Martha

doi:10.1016/s0015-0282(02)04838-0

Cited by 33 publications

(33 citation statements)

References 30 publications

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“…Our later observation is supported by the previous reports indicating that the activity of MMP2 in serum (Gomes et al 2011) or follicular fluid (Lahav-Baratz et al 2003) does not alter in PCOS. However, there is no such a record in the literature about MMP9, since the activity of MMP9 has not been previously investigated in PCOS.…”

Section: Discussionsupporting

confidence: 91%

“…Substrate gel electrophoresis (zymography) for the determination of MMP2, MMP9 and MMP9/NGAL activities Gelatinolytic activities of MMP2, MMP9 and MMP9/NGAL complex in serum samples were assessed by zymography, as previously described with some modifications (Lahav-Baratz et al 2003, Goncalves et al 2009, Tsai et al 2011. Briefly, samples were subjected to electrophoresis on a 10% polyacrylamide-SDS gel (PAGE) co-polymerized with 1% gelatin as a substrate.…”

Section: Biochemical Analysismentioning

confidence: 99%

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Matrix metalloproteinases 2 and 9 and MMP9/NGAL complex activity in women with PCOS

et al. 2016

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It is believed that matrix metalloproteinases (MMPs) play important roles in follicular development and pathogenesis of polycystic ovary syndrome (PCOS). However, conflicting results are available about the alteration of MMP2 and MMP9 concentrations or activities in PCOS. In fact, there is no study entirely investigating both concentration and activity of these MMPs and serum levels of their tissue inhibitors TIMP2 and TIMP1, as well as lipocalin-bound form of MMP9 (MMP9/NGAL). Therefore, the thoroughness of previous studies is questionable. This study was conducted to determine circulatory concentration of MMP2, MMP9, MMP9/NGAL complex, TIMP1 and TIMP2 as well as gelatinase activities of MMP2, MMP9 and MMP9/NGAL complex in women with PCOS and controls. Mean age and BMI as well as serum levels of total cholesterol, triacylglycerol, HDL-C, LDL-C, fasting blood sugar (FBS), insulin, estradiol and sex hormone-binding globulin did not differ between groups, whereas a marked decrease in FSH and significant increases in LH, LH/FSH ratio, testosterone and free androgen index were observed. Women with PCOS and controls showed closed concentrations of MMP2, MMP9, MMP9/NGAL, TIMP1 and TIMP2. Gelatinase activity of MMP9 was found significantly higher in PCOS than in controls (64.53G15.32 vs 44.61G18.95 respectively) while patients and healthy subjects showed similar activities of MMP2 and MMP9/NGAL complex. Additionally, PCOS patients showed a higher MMP9/TIMP1 ratio compared with control women. Direct correlations were also observed between circulatory MMP9 level and the concentration and activity of MMP9/NGAL complex. In conclusion, based on the results of present study, we believe that MMP9 may be involved in the pathogenesis of PCOS.Reproduction (2016) 151 305-311

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Section: Discussionsupporting

confidence: 91%

Section: Biochemical Analysismentioning

confidence: 99%

Matrix metalloproteinases 2 and 9 and MMP9/NGAL complex activity in women with PCOS

et al. 2016

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“…Study has found that decreased FF IrCRH levels are correlated with oocyte dysfunction in women with PCOS (Mastorakos et al ., 1994). Other reports suggest that FF tissue inhibitor of metalloproteinase (TIMP)-1 & 2 levels are significantly lower in women with PCOS than in NOW (Lahav-Bratz et al ., 2003). In contrast, there was no difference in basal production of TIMP-1 by cells in culture between women with PCOS and NOW; however, matrix metalloproteinases-2 and 9 are significantly increased in the FF of women with PCOS (Shalev et al ., 2001), suggesting an association with inappropriate atresia.…”

Section: Intra-ovarian Factorsmentioning

confidence: 99%

“…(2010)Matrix metalloproteinase 2/9↑ or ≈Shalev et al . (2001), Lahav-Bratz et al . (2003)Nerve growth factor↑ or ↓Dissen et al .…”

Section: Introductionmentioning

confidence: 99%

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Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence

Qiao

Feng

2010

Human Reproduction Update

396

314

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BACKGROUNDPolycystic ovary syndrome (PCOS) is a common metabolic dysfunction and heterogeneous endocrine disorder in women of reproductive age. Although patients with PCOS are typically characterized by increased numbers of oocytes retrieved during IVF, they are often of poor quality, leading to lower fertilization, cleavage and implantation rates, and a higher miscarriage rate.METHODSFor this review, we searched the database MEDLINE (1950 to January 2010) and Google for all full texts and/or abstract articles published in English with content related to oocyte maturation and embryo developmental competence.RESULTSThe search showed that alteration of many factors may directly or indirectly impair the competence of maturating oocytes through endocrine and local paracrine/autocrine actions, resulting in a lower pregnancy rate in patients with PCOS. The extra-ovarian factors identified included gonadotrophins, hyperandrogenemia and hyperinsulinemia, although intra-ovarian factors included members of the epidermal, fibroblast, insulin-like and neurotrophin families of growth factors, as well as the cytokines.CONCLUSIONSAny abnormality in the extra- and/or intra-ovarian factors may negatively affect the granulosa cell–oocyte interaction, oocyte maturation and potential embryonic developmental competence, contributing to unsuccessful outcomes for patients with PCOS who are undergoing assisted reproduction.

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Metformin treatment alleviates polycystic ovary syndrome by decreasing the expression of MMP‐2 and MMP‐9 via H19/miR‐29b‐3p and AKT/mTOR/autophagy signaling pathways

Chen

Wei

Zhao

et al. 2019

Journal Cellular Physiology

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In this study, we aimed to investigate the molecular pathway(s) underlying the effect of metformin (MET) on the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Real-time polymerase chain reaction, Western blot analysis, and gelatin zymography were used to assay the effects of MET on MMP and AMPK signaling pathways. In addition, HTOG cells were treated with miR-29b-3p/a scramble control, H19/a negative control, or MET/PBS to explore possible signaling pathway(s) underlying the inhibitory effect of MET on MMP-2/MMP-9. A rat model of polycystic ovary syndrome (PCOS) was also established to validate the molecular mechanism(s) of MET in vivo. The administration of MET suppressed the expression of MMP-9/ MMP-2 and mTOR while increasing the expression of Akt and AMPK, indicating that MET reduced the expression of MMPs via the AMPK signaling pathway. Meanwhile, the H19/miR-29b-3p/MMP-9 and H19/miR-29b-3p/MMP-2 signaling pathways were implicated in PCOS, in which the interactions between H19/miR-29b-3p and MMP-9/ MMP-2/miR-29b-3p were confirmed. Furthermore, the administration of MET suppressed the expression of H19 while elevating the expression of miR-29b-3p. And the role of MET in PCOS was also confirmed in vivo via examining the activity of H19 and AMPK signaling pathways in cell or serum samples collected from PCOS rats. MET exhibits a therapeutic effect in the treatment of PCOS by reducing the expression of MMPs. K E Y W O R D S Akt, autophagy, H19, MET, miR-29b-3p, MMP-2, MMP-9, mTOR, PCOS

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Decreased expression of tissue inhibitor of matrix metalloproteinases in follicular fluid from women with polycystic ovaries compared with normally ovulating patients undergoing in vitro fertilization

Cited by 33 publications

References 30 publications

Matrix metalloproteinases 2 and 9 and MMP9/NGAL complex activity in women with PCOS

Matrix metalloproteinases 2 and 9 and MMP9/NGAL complex activity in women with PCOS

Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence

Metformin treatment alleviates polycystic ovary syndrome by decreasing the expression of MMP‐2 and MMP‐9 via H19/miR‐29b‐3p and AKT/mTOR/autophagy signaling pathways

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