ADAMTS1 Cleavage of Versican Mediates Essential Structural Remodeling of the Ovarian Follicle and Cumulus-Oocyte Matrix During Ovulation in Mice1

Brown, Hannah; Dunning, Kylie R.; Robker, Rebecca L.; Boerboom, Derek; Pritchard, Melanie April; Lane, Michelle; Russell, Darryl L.

doi:10.1095/biolreprod.110.084434

Cited by 136 publications

(122 citation statements)

References 43 publications

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“…Finally, it is likely that cathepsin L and ADAMTS-1 are both integral mediators of ovulation and that a coordinated disruption in both is required to prevent ovulation. This conclusion is, in fact, supported by the partial reduction in ovulation of the ADAMTS-1 null mice [3] and the anovulatory phenotype of the progesterone receptor null mice [2] where neither ADAMTS-1 nor cathepsin L are induced.…”

Section: Discussionmentioning

confidence: 89%

“…There is growing evidence, derived from the study of genetically-modified mouse models that certain proteases, specifically cathepsin L and ADAMTS-1, participate in follicular rupture and perhaps other aspects of ovulation and fertilization [2,3,6,13]. This is particularly true for ADAMTS-1 because mice that are null for this enzyme have a substantial defect in ovulation that is secondary to a defect in follicular rupture [3].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…This is particularly true for ADAMTS-1 because mice that are null for this enzyme have a substantial defect in ovulation that is secondary to a defect in follicular rupture [3]. In addition, the fertilization rate of ovulated oocytes is reduced in ADAMTS-1 null mice [3]. The involvement of cathepsin L on fertility is not as well defined but, like ADAMTS-1, the expression of cathepsin L is enhanced in the periovulatory period and is dependent on the expression of the granulosa cell progesterone receptor [2,14].…”

Section: Discussionmentioning

confidence: 99%

“…Cathepsin L (CTSL, a lysosomal cysteine protease) and ADAMTS-1 (A distegrin and metalloproteinase with thrombospondin-like motifs), both selectively induced in granulosa cells by LH during the periovulatory period in wild-type mice, remained at preovulatory levels in anovulatory progesterone receptor (PR) knockout mice [2]. Conclusive evidence for the role of ADAMTS-1 in remodeling of the follicular wall to mediate rupture was morphologically and histologically identified in an ADAMTS-1 knockout mouse model, which resulted in a subfertile phenotype with significant reduction in the ovulation rate and the fertilization rate of ovulated oocytes [3]. While the role of cathepsin L in ovulation has not been studied in detail, homozygous female cathepsin L null mice are reportedly infertile [4].…”

Section: Introductionmentioning

confidence: 99%

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Do alterations in follicular fluid proteases contribute to human infertility?

Cookingham

Voorhis

Ascoli

2015

J Assist Reprod Genet

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Purpose Cathepsin L and ADAMTS-1 are known to play critical roles in follicular rupture, ovulation, and fertility in mice. Similar studies in humans are limited; however, both are known to increase during the periovulatory period. No studies have examined either protease in the follicular fluid of women with unexplained infertility or infertility related to advanced maternal age (AMA). We sought to determine if alterations in cathepsin L and/or ADAMTS-1 existed in these infertile populations. Methods Patients undergoing in vitro fertilization (IVF) for unexplained infertility or AMA-related infertility were prospectively recruited for the study; patients with tubal or male factor infertility were recruited as controls. Follicular fluid was collected to determine gene expression (via quantitative polymerase chain reaction), enzyme concentrations (via enzyme-linked immunosorbent assays), and enzymatic activities (via fluorogenic enzyme cleavage assay or Western blot analysis) of cathepsin L and ADAMTS-1. Results The analysis included a total of 42 patients (14 per group). We found no statistically significant difference in gene expression, enzyme concentration, or enzymatic activity of cathepsin L or ADAMTS-1 in unexplained infertility or AMA-related infertility as compared to controls. We also found no statistically significant difference in expression or concentration with advancing age. Conclusions Cathepsin L and ADAMTS-1 are not altered in women with unexplained infertility or AMA-related infertility undergoing IVF, and they do not decline with advancing age. It is possible that differences exist in natural cycles, contributing to infertility; however, our findings do not support a role for protease alterations as a common cause of infertility.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Do alterations in follicular fluid proteases contribute to human infertility?

Cookingham

Voorhis

Ascoli

2015

J Assist Reprod Genet

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Single‐cell RNA sequencing reveals a mechanism underlying the susceptibility of the left atrial appendage to intracardiac thrombogenesis during atrial fibrillation

Yang

Sun

et al. 2023

Clinical & Translational Med

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Background Atrial fibrillation (AF) is associated with an increased risk of thrombosis of the left atrial appendage (LAA). However, the molecular mechanisms underlying this site‐specificity remain poorly understood. Here, we present a comparative single‐cell transcriptional profile of paired atrial appendages from patients with AF and illustrate the chamber‐specific properties of the main cell types. Methods Single‐cell RNA sequencing analysis of matched atrial appendage samples from three patients with persistent AF was evaluated by 10× genomics. The AF mice model was created using Tbx5 knockout mice. Validation experiments were performed by glutathione S‐transferase pull‐down assays, coimmunoprecipitation (Co‐IP), cleavage assays and shear stress experiments in vitro. Results In LAA, phenotype switching from endothelial cells to fibroblasts and inflammation associated with proinflammatory macrophage infiltration were observed. Importantly, the coagulation cascade is highly enriched in LAA endocardial endothelial cells (EECs), accompanying the up‐regulation of a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) and the down‐regulation of the tissue factor pathway inhibitor (TFPI) and TFPI2. Similar alterations were verified in an AF mouse model (Tbx5+/−) and EECs treated with simulated AF shear stress in vitro. Furthermore, we revealed that the cleavage of both TFPI and TFPI2 based on their interaction with ADAMTS1 would lead to loss of anticoagulant activities of EECs. Conclusions This study highlights the decrease in the anticoagulant status of EECs in LAA as a potential mechanism underlying the propensity for thrombosis, which may aid the development of anticoagulation therapeutic approaches targeting functionally distinct cell subsets or molecules during AF.

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The metalloproteinase ADAMTS1: A comprehensive review of its role in tumorigenic and metastatic pathways

Tan

Ricciardelli

Russell

2013

Intl Journal of Cancer

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As it was first characterized in 1997, the ADAMTS (A Disintegrin and Metalloprotease with ThromboSpondin motifs) metalloprotease family has been associated with many physiological and pathological conditions. Of the 19 proteases belonging to this family, considerable attention has been devoted to the role of its first member ADAMTS1 in cancer. Elevated ADAMTS1 promotes pro-tumorigenic changes such as increased tumor cell proliferation, inhibited apoptosis and altered vascularization. Importantly, it facilitates significant peritumoral remodeling of the extracellular matrix environment to promote tumor progression and metastasis. However, discrepancy exists, as several studies also depict ADAMTS1 as a tumor suppressor. This article reviews the current understanding of ADAMTS1 regulation and the consequence of its dysregulation in primary cancer and ADAMTS1-mediated pathways of cancer progression and metastasis.In cancer, the remodeling of the host tissue environment is fundamental for the dismantling of normal tissue structural constraints, establishment of vascular supply and invasion of metastatic cells. For this aberrant remodeling to occur, cancers cells rely on the proteolytic activity of extracellular matrix (ECM) proteases to facilitate the degradation of structural proteins that make up the ECM. 1,2 Metalloproteases belonging to the ADAMTS family have been widely implicated in tissue remodeling events manifested in cancer development, growth and progression. [3][4][5][6][7][8][9][10][11][12][13][14] There are 19 ADAMTS proteases identified in humans. They share homology in the catalytic ADAM-metalloprotease and disintegrin domains, but differ in the variable numbers of thrombospondin-like motifs and other carboxyl-terminal domains associated with ECM interaction. 15,16 Unlike the transmembrane ADAM family, ADAMTS proteases are secreted and bind to the ECM through their C-terminal regions. 17 33 Among them, the modulated expression of ADAMTS1 has been the most characterized in cancer and is the focus of this review.ADAMTS1 was initially described as a mediator of inflammation 34 but its activity has since become appreciated in organogenesis, [35][36][37][38] blood/lymph vessel formation, [39][40][41][42][43][44][45] ovarian folliculogenesis 39 and ovulation. 23,46 In these physiological events, ADAMTS1 remodels the ECM through the proteolytic degradation of key substrates such as chondroitin sulfated proteoglycans [47][48][49][50] and collagen. 51-53 ADAMTS1 also acts as an inhibitor of angiogenesis by sequestering proangioigenic stimuli, vascular epithelial growth factor (VEGF) and preventing its interaction with its receptor. 41,45 The dysregulation of ADAMTS1 often leads to pathological manifestations of altered ECM 54-56 and/or vascular density 57-60 and many studies have highlighted its functional activity during tumorigenic transformation. 14,[61][62][63][64][65][66][67] ADAMTS1 dysregulation is linked to four of the most commonly diagnosed cancers. But, conflicting reports currently surround its exp...

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ADAMTS1 Cleavage of Versican Mediates Essential Structural Remodeling of the Ovarian Follicle and Cumulus-Oocyte Matrix During Ovulation in Mice1

Cited by 136 publications

References 43 publications

Do alterations in follicular fluid proteases contribute to human infertility?

Do alterations in follicular fluid proteases contribute to human infertility?

Single‐cell RNA sequencing reveals a mechanism underlying the susceptibility of the left atrial appendage to intracardiac thrombogenesis during atrial fibrillation

The metalloproteinase ADAMTS1: A comprehensive review of its role in tumorigenic and metastatic pathways

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