Matrix metalloproteinase and tissue inhibitors of metalloproteinases gene polymorphisms in disorders that influence fertility and pregnancy complications: A systematic review and meta-analysis

Barišić, Anita; Pavlić, Sanja Dević; Ostojić, Saša; Pereza, Nina

doi:10.1016/j.gene.2018.01.010

Cited by 22 publications

(16 citation statements)

References 69 publications

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“…These findings are in accordance with our suggestion that inflammation may contribute to creating the collagenolytic microenvironment that induces miscarriage like term labor. Some studies have focused on genotype analysis of matrix metalloproteinases including the MMP-9 gene polymorphism but found no significant differences between spontaneous abortion or other placental disorders and control groups (35,36).…”

Section: Discussionmentioning

confidence: 99%

Differential expression of egfr-1, mmp-3, and mmp-9 in spontaneous abortions, induced abortions, and tubal pregnancies

Balcı

Ozdemir²

2018

TJPATH

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Objective: The purpose of our study was to assess trophoblastic and uterine sufficiency in miscarriage pathogenesis with immunohistochemical methods and to determine if they could be used as a screening tool for the risk of miscarriage in the future. Material and Method: Placental tissue specimens that were comprised of 20 spontaneous abortions, 23 voluntarily terminated (induced) abortions, and 12 tubal pregnancies were included in this study. Trophoblastic cells and implantation area were evaluated for staining with EGFR-1, MMP-3, and MMP-9 by immunohistochemistry. Results: EGFR-1 expression was more intense and diffuse in decidual cells in the placental bed of spontaneous abortion specimens; this difference was statistically significant (P=0.004). MMP-3 expression was markedly increased in villous and extravillous trophoblastic cells in induced abortions; the difference between the groups was found to be statistically significant (P values ranged from < 0.01 to 0.005). MMP-9 expression tended to be higher in spontaneous abortion and tubal pregnancy specimens, and the results were statistically significant as P values were lower than 0.01. Conclusion: Higher EGFR-1 expression in the decidual tissue of spontaneous abortion specimens suggests that EGFR-1 triggers the migration of extravillous trophoblasts, leading to their destructive invasion. Similarly, MMP-9 immunopositivity might be indicative of aggressive invasion contributing to spontaneous abortion pathogenesis. Relatively high levels of MMP-3 expression in induced abortion specimens used as a control group might be a predictor of successful implantation, whereas its decreased expression might be indicative of risk for pregnancy loss.

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Section: Discussionmentioning

confidence: 99%

Differential expression of egfr-1, mmp-3, and mmp-9 in spontaneous abortions, induced abortions, and tubal pregnancies

Balcı

Ozdemir²

2018

TJPATH

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“…Therefore, aberrant regulation of matrix metalloproteases may be the primary cause of endometrial lesion formation in a group of predisposed women. The relationship between endometriosis and MMPs has long been known, and it is widely demonstrated in the literature; in fact, endometrium derived from women with endometriosis shows higher proteolytic activity than endometrium from healthy controls [21][22][23]. However, the studies conducted on human endometriotic tissues are conflicting because of the intervention of numerous variables influencing the results.…”

Section: Introductionmentioning

confidence: 99%

Expression of Matrix Metalloproteinases and Their Inhibitors in Endometrium: High Levels in Endometriotic Lesions

Luddi

Marrocco

Governini

et al. 2020

IJMS

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Endometriosis is a condition defined as presence of endometrium outside of the uterine cavity. These endometrial cells are able to attach and invade the peritoneum or ovary, thus forming respectively the deep infiltrating endometriosis (DIE) and the ovarian endometrioma (OMA), the ectopic lesions feature of this pathology. Endometriotic cells display high invasiveness and share some features of malignancy with cancer cells. Indeed, the tissue remodeling underlining lesion formation is achieved by matrix metalloproteinases (MMPs) and their inhibitors. Therefore, these molecules are believed to play a key role in development and pathogenesis of endometriosis. This study investigated the molecular profile of metalloproteinases and their inhibitors in healthy (n = 15) and eutopic endometrium (n = 19) in OMA (n = 10) and DIE (n = 9); moreover, we firstly validated the most reliable housekeeping genes allowing accurate gene expression analysis in these tissues. Gene expression, Western blot, and immunofluorescence analysis of MMP2, MMP3, and MMP10 and their tissue inhibitors TIMP1 and TIMP2 demonstrated that these enzymes are finely tuned in these tissues. In OMA lesions, all the investigated MMPs and their inhibitors were significantly increased, while DIE expressed high levels of MMP3. Finally, in vitro TNFα treatment induced a significant upregulation of MMP3, MMP10, and TIMP2 in both healthy and eutopic endometrial stromal cells. This study, shedding light on MMP and TIMP expression in endometriosis, confirms that these molecules are altered both in eutopic endometrium and endometriotic lesions. Although further studies are needed, these data may help in understanding the molecular mechanisms involved in the extracellular matrix remodeling, a crucial process for the endometrial physiology.

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“…Recently, localized polymorphisms identi ed in the promoter region of MMP-2 (-1306 C/T; rs 243865) and MMP-9 (-1562 C/T; rs 3918242) were found to induce changes in the levels of transcription and or expression of the protein. These mutations have been proposed as a risk factor for spontaneous abortion [50,59]. Regarding the three patients of the present study with implanted embryos that spontaneously aborted (P52, P57, and P58), the corresponding culture media displayed proMMP-2 and proMMP-9 (Fig.…”

Section: Discussionmentioning

confidence: 64%

Differential proMMP-2 and proMMP-9 Secretion in Human Pre-implantation Embryos at Day 5 of Development.

Olvera-Valencia

Acuña-González

Iyune-Cojab

et al. 2021

Preprint

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Background: The most commonly used non-invasive criterion for evaluating the probable success of transferring in vitro human embryos for implantation is their morphological development. With this criterion, however, embryos in cellular arrests go unnoticed. Extracellular matrix metalloproteases type 2 (MMP-2) and MMP-9 are key markers of embryonic development and the implantation process, according to various animal studies. The current study investigated the proMMP-2 and proMMP-9 expression in the culture media developing human embryos that were transferred for implantation. Methods: Forty-two patients were accepted in the Department of Reproductive Biology of a Hospital in México City, based on the Institutional inclusion criteria for in vitro fertilization. On day 5 of development, embryos were transferred to women, and the culture medium was stored at -70 to await assessment of the activity of proMMP-2 and proMMP-9 in substrate gel zymography. Results: The patients showing embryo sac development were assigned to the pregnant group (n =17) or non-pregnant (n =25). In both groups, the activity of proMMP-2 and proMMP-9 was evaluated in substrate gel zymography. Our results indicate for all 17 women able to achieve a full-term pregnancy, the activity band of proMMP-2 was found in the corresponding culture medium. For 11 of them, the band of proMMP-9. Regarding the other 25 patients, the expression band for proMMP-2 detected in 3 and that proMMP-9 in 11 individuals. Conclusions: On day 5 of embryo development, the evaluation of proMMP-2 and proMMP-9 in the embryo culture medium is a reliable indicator of embryo quality and capacity to establish pregnancy.

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Matrix metalloproteinase and tissue inhibitors of metalloproteinases gene polymorphisms in disorders that influence fertility and pregnancy complications: A systematic review and meta-analysis

Cited by 22 publications

References 69 publications

Differential expression of egfr-1, mmp-3, and mmp-9 in spontaneous abortions, induced abortions, and tubal pregnancies

Differential expression of egfr-1, mmp-3, and mmp-9 in spontaneous abortions, induced abortions, and tubal pregnancies

Expression of Matrix Metalloproteinases and Their Inhibitors in Endometrium: High Levels in Endometriotic Lesions

Differential proMMP-2 and proMMP-9 Secretion in Human Pre-implantation Embryos at Day 5 of Development.

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