Matrix metalloproteinase 9 is a distal-less 3 target-gene in placental trophoblast cells

Clark, Patricia A.; Xie, Jian‐Jun; Li, Sha; Zhang, Xuesen; Coonrod, Scott A.; Roberson, Mark S.

doi:10.1152/ajpcell.00205.2012

Cited by 5 publications

(4 citation statements)

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“…The essential role of DLX3 in placental development was first described in Dlx3 loss‐of‐function mice (Morasso et al, ). We and others have identified the involvement of DLX3 in multiple molecular pathways important for placental morphogenesis and function in mice and humans: DLX3 has been proposed to facilitate the production of human chorionic gonadotropin (hCG), a luteotropic hormone crucial for implantation and early pregnancy recognition in humans (Cole, ), through upregulating CGA which encodes a common subunit of the glycoprotein hormones (Roberson et al, ); DLX3 was also shown to regulate MMP9 expression in mouse placentae and human trophoblast cell line, therefore contributing to uterine extracellular matrix degradation and maternal spiral artery remodeling (Clark et al, ; Han et al, ). Genetic loss of Mmp9 in the murine model has been demonstrated to cause maternal hypertension late in gestation similar to preeclampsia, creating a potential link between DLX3, MMP9 and preeclampsia‐like conditions (Plaks et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Like Gcm1 , Dlx3 loss‐of‐function mutation in mice leads to embryonic mortality at mid‐gestation characterized by placental deficiency in the labyrinth (Morasso et al, ). Our previous work in this area identified placental specific target genes of DLX3, including the g lycoprotein hormone alpha subunit ( CGA ) and matrix metalloproteinase 9 ( MMP9 ) (Clark et al, ; Han et al, ; Roberson, Meermann, Morasso, Mulvaney‐Musa, & Zhang, ), both of which are critical for pregnancy establishment and placental development in humans (Cole, ; Plaks et al, ). To obtain a more comprehensive understanding of the DLX3 ‐dependent transcriptome, we performed microarray analyses in placentae of Dlx3 null and wild‐type mice, where loss of Dlx3 was correlated with marked downregulation of Pgf in the mouse placenta due to a loss of the direct effects of Dlx3 on the murine Pgf promoter activity (Han et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Dlx3 and GCM‐1 functionally coordinate the regulation of placental growth factor in human trophoblast‐derived cells

Roberson

2017

Journal Cellular Physiology

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Placental growth factor (PGF) is abundantly expressed by trophoblast cells within human placentae and is important for trophoblast development and placental vascularization. Circulating maternal serum levels of PGF are dynamically upregulated across gestation in normal pregnancies, whereas low circulating levels and placental production of PGF have been implicated in the pathogenesis of preeclampsia and other gestational diseases. However, the underlying molecular mechanism of regulating PGF expression in the human placenta remains poorly understood. In this study, we demonstrated that transcription factors Distal-less 3 (DLX3) and Glial cell missing-1 (GCM1) were both sufficient and required for PGF expression in human trophoblast-derived cells by overexpression and knockdown approaches. Surprisingly, while DLX3 and GCM1 were both positive regulators of PGF, co-overexpression of DLX3 and GCM1 led to an antagonist effect on PGF expression on the endogenous gene and a luciferase reporter. Further, deletion and site-directed mutagenesis studies identified a novel regulatory element on the PGF promoter mediating both DLX3- and GCM1-dependent PGF expression. This regulatory region was also found to be essential for the basal activity of the PGF promoter. Finally, Chromatin-immunoprecipitation (ChIP) assays revealed colocalization of DLX3 and GCM1 at the identified regulatory region on the PGF promoter. Taken together, our studies provide important insights into intrinsic regulation of human placental PGF expression through the functional coordination of DLX3 and GCM1, and are likely to further the understanding of pathogenesis of PGF dysregulation in preeclampsia and other disease conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dlx3 and GCM‐1 functionally coordinate the regulation of placental growth factor in human trophoblast‐derived cells

Roberson

2017

Journal Cellular Physiology

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“…MMPs play an important role in the remodeling of different structural and support components during ovulation (Smith et al, 2002;Rosewell et al, 2015), decidualization (Jones et al, 2006;Sharma et al, 2016), and implantation (Wang et al, 2003;Shokry et al, 2009;Clark et al, 2013). The main findings of the current study in relation to the activity of proMMP-2 and proMMP-9 in the culture media at day 5 of embryonic development can be summarized in five points.…”

Section: Discussionmentioning

confidence: 79%

Differential proMMP-2 and proMMP-9 secretion in human pre-implantation embryos at day 5 of development

et al. 2022

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Morphological development is the most common noninvasive criterion used to select in vitro human embryos for implantation. With this criterion, however, embryos in cellular arrest go unnoticed. A more accurate criterion is needed to improve the success rate of implantation. 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 first objective of this study was to examine proMMP-2 and proMMP-9 activity in the culture media of human embryos with good morphological development. Secondly, the results of proMMP-2 and proMMP-9 activity in the culture medium were compared between pregnant and non-pregnant. Forty-two patients were approved by the Ethics and Research Committees of the Instituto Nacional de Perinatología in México City hospital, based on institutional inclusion criteria for in vitro fertilization. On day 5 of development, embryos were transferred to patients, and the culture media secretion profile of proMMP-2 and proMMP-9 activity was determined by substrate gel zymography. After analysis of embryo sac development, each patient was assigned to the pregnant (n=17) or non-pregnant (n=25) group. Our results demonstrate that proMMP-2 was active in the culture media corresponding to all 17 women achieving full-term pregnancy and proMMP-9 in the media corresponding to 11 of these women. Contrarily proMMP-2 and proMMP-9 were active in the culture media corresponding to 3 and 11 of the 25 non-pregnant patients, respectively. The clinical implications of this study suggest the activity evaluation of proMMP-2 and proMMP-9 in embryonic culture media on day 5 of development appears to be a reliable indicator of the quality of embryos and their capacity to establish a pregnancy.

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“…MMPs play an important role in the remodeling of different structural and support components during ovulation [40,41] decidualization [42,43], and implantation [44][45][46]. The main ndings of the present study can be summarized in ve points in relation to the activity of proMMP-2 and proMMP-9 in the culture media of the embryos on day 5 of their development 1) the activity of proMMP-2 was found in 14 of 14 culture media corresponding to the patients who achieved a full-term pregnancy and in 3 of 25 culture media associated with women who did not have this outcome.…”

Section: Discussionmentioning

confidence: 99%

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 9 is a distal-less 3 target-gene in placental trophoblast cells

Cited by 5 publications

References 43 publications

Dlx3 and GCM‐1 functionally coordinate the regulation of placental growth factor in human trophoblast‐derived cells

Dlx3 and GCM‐1 functionally coordinate the regulation of placental growth factor in human trophoblast‐derived cells

Differential proMMP-2 and proMMP-9 secretion in human pre-implantation embryos at day 5 of development

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

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