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Localization of chondromodulin-I at the feto-maternal interface and its inhibitory actions on trophoblast invasion in vitro.

ABSTRACT: BACKGROUND:Chondromodulin-I (ChM-I) is an anti-angiogenic glycoprotein that is specifically localized at the extracellular matrix of the avascular mesenchyme including cartilage and cardiac valves. In this study, we characterized the expression pattern of ChM-I during early pregnancy in mice in vivo and its effect on invasion of trophoblastic cells into Matrigel in vitro. RESULTS:Northern blot analysis clearly indicated that ChM-I transcripts were expressed in the pregnant mouse uterus at 6.5-9.5 days post coitum. In situ hybridization and immunohistochemistry revealed that ChM-I was localized to the mature decidua surrounding the matrix metalloproteinase-9 (MMP-9)-expressing trophoblasts. Consistent with this observation, the expression of ChM-I mRNA was induced in decidualizing endometrial stromal cells in vitro, in response to estradiol and progesterone. Recombinant human ChM-I (rhChM-I) markedly inhibited the invasion through Matrigel as well as the chemotactic migration of rat Rcho-1 trophoblast cells in a manner independent of MMP activation. CONCLUSIONS:This study demonstrates the inhibitory action of ChM-I on trophoblast migration and invasion, implying the potential role of the ChM-I expression in decidual cells for the regulated tissue remodeling and angiogenesis at feto-maternal interface.

SUBMITTER: Miura S

PROVIDER: S-EPMC3171719 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Localization of chondromodulin-I at the feto-maternal interface and its inhibitory actions on trophoblast invasion in vitro.

Miura Shigenori S Shukunami Chisa C Mitsui Kaori K Kondo Jun J Hiraki Yuji Y

BMC cell biology 20110818

<h4>Background</h4>Chondromodulin-I (ChM-I) is an anti-angiogenic glycoprotein that is specifically localized at the extracellular matrix of the avascular mesenchyme including cartilage and cardiac valves. In this study, we characterized the expression pattern of ChM-I during early pregnancy in mice in vivo and its effect on invasion of trophoblastic cells into Matrigel in vitro.<h4>Results</h4>Northern blot analysis clearly indicated that ChM-I transcripts were expressed in the pregnant mouse u ...[more]

PMID: 21849085

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Project description:The placenta and fetal membrane act as a protective barrier throughout pregnancy while maintaining communication and nutrient exchange between the baby and the mother. Disruption of this barrier leads to various pregnancy complications, including preterm birth, which can have lasting negative consequences. Thus, understanding the role of the feto-maternal interface during pregnancy and parturition is vital to advancing basic and clinical research in the field of obstetrics. However, human subject studies are inherently difficult, and appropriate animal models are lacking. Due to these challenges, in vitro cell culture-based studies are most commonly utilized. However, the structure and functions of conventionally used in vitro 2D and 3D models are vastly different from the in vivo environment, making it difficult to fully understand the various factors affecting pregnancy as well as pathways and mechanisms contributing to term and preterm births. This limitation also makes it difficult to develop new therapeutics. The emergence of in vivo-like in vitro models such as organ-on-chip (OOC) platforms can better recapitulate in vivo functions and responses and has the potential to move this field forward significantly. OOC technology brings together two distinct fields, microfluidic engineering and cell/tissue biology, through which diverse human organ structures and functionalities can be built into a laboratory model that better mimics functions and responses of in vivo tissues and organs. In this review, we first provide an overview of the OOC technology, highlight two major designs commonly used in achieving multi-layer co-cultivation of cells, and introduce recently developed OOC models of the feto-maternal interface. As a vital component of this review, we aim to outline progress on the practicality and effectiveness of feto-maternal interface OOC (FM-OOC) models currently used and the advances they have fostered in obstetrics research. Lastly, we provide a perspective on the future basic research and clinical applications of FM-OOC models, and even those that integrate multiple organ systems into a single OOC system that may recreate intrauterine architecture in its entirety, which will accelerate our understanding of feto-maternal communication, induction of preterm labor, drug or toxicant permeability at this vital interface, and development of new therapeutic strategies.

Project description:Maternal infection (i.e., ascending infection) and the resulting host inflammatory response are risk factors associated with spontaneous preterm birth (PTB), a major pregnancy complication. However, the path of infection and its propagation from the maternal side to the fetal side have been difficult to study due to the lack of appropriate in vitro models and limitations of animal models. A better understanding of the propagation kinetics of infectious agents and development of the host inflammatory response at the feto-maternal (amniochorion-decidua, respectively) interface (FMi) is critical in curtailing host inflammatory responses that can lead to PTB. To model ascending infection and determine inflammatory responses at the FMi, we developed a microfluidic organ-on-chip (OOC) device containing primary cells from the FMi (decidua, chorion, and amnion [mesenchyme and epithelium]) and collagen matrix harvested from primary tissue. The FMi-OOC is composed of four concentric circular cell/collagen chambers designed to mimic the thickness and cell density of the FMi in vivo. Each layer is connected by arrays of microchannels filled with type IV collagen to recreate the basement membrane of the amniochorion. Cellular characteristics (viability, morphology, production of nascent collagen, cellular transitions, and migration) in the OOC were similar to those seen in utero, validating the physiological relevance and utility of the developed FMi-OOC. The ascending infection model of the FMi-OOC, triggered by exposing the maternal (decidua) side of the OOC to lipopolysaccharide (LPS, 100 ng mL-1), shows that LPS propagated through the chorion, amnion mesenchyme, and reached the fetal amnion within 72 h. LPS induced time-dependent and cell-type-specific pro-inflammatory cytokine production (24 h decidua: IL-6, 48 h chorion: GM-CSF and IL-6, and 72 h amnion mesenchyme and epithelium: GM-CSF and IL-6). Collectively, this OOC model and study successfully modeled ascending infection, its propagation, and distinct inflammatory response at the FMi indicative of pathologic pathways of PTB. This OOC model provides a novel platform to study physiological and pathological cell status at the FMi, and is expected to have broad utility in the field of obstetrics.

Dataset Information

Localization of chondromodulin-I at the feto-maternal interface and its inhibitory actions on trophoblast invasion in vitro.

Publications

Localization of chondromodulin-I at the feto-maternal interface and its inhibitory actions on trophoblast invasion in vitro.

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