MTiness in pseudo-malignant behavior of trophoblasts during embryo implantation

Dhar, Ruby; Singh, Sunil; Mukherjee, Indrani; Pethusamy, Karthikeyan; Purkayastha, Kakali; Das, Prasenjit; Sharma, Jai Bhagwan; Sharma, Radhey Shyam; Karmakar, Subhradip

doi:10.2741/4915

Cited by 6 publications

(6 citation statements)

References 85 publications

(124 reference statements)

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“…We have shown that TGF-β1 inhibits human EVT cell invasion by inducing Snail-mediated down-regulation of the expression of vascular endothelial-cadherin (VE-cadherin) [ 9 ]. Notably, EMT has now been considered an important process that regulates EVT cell invasion [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Snail mediates GDF-8-stimulated human extravillous trophoblast cell invasion by upregulating MMP2 expression

et al. 2023

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Background Extravillous trophoblast (EVT) cell invasion is a tightly regulated process that requires for a normal pregnancy. The epithelial-mesenchymal transition (EMT) has been implicated in EVT cell invasion. Growth differentiation factor-8 (GDF-8), a member of the transforming growth factor-beta (TGF-β) superfamily, is expressed in the human placenta and promotes EVT cell invasion by upregulating the expression of matrix metalloproteinase 2 (MMP2). However, the underlying molecular mechanism of GDF-8-induced MMP2 expression remains undetermined. Therefore, the present study aims to examine the role of Snail and Slug, the EMT-related transcriptional regulators, in GDF-8-stimulated MMP2 expression and cell invasion in HTR-8/SVneo human EVT cell line and primary cultures of human EVT cells. Methods HTR-8/SVneo and primary cultures of human EVT cells were used to examine the effect of GDF-8 on MMP2 expression and explore the underlying mechanism. For gene silencing and overexpression, the HTR-8/SVneo cell line was used to make the experiments more technically feasible. The cell invasiveness was measured by Matrigel-coated transwell invasion assay. Results GDF-8 stimulated MMP2 expression in both HTR-8/SVneo and primary EVT cells. The stimulatory effect of GDF-8 on MMP2 expression was blocked by the inhibitor of TGF-β type-I receptors, SB431542. Treatment with GDF-8 upregulated Snail and Slug expression in both HTR-8/SVneo and primary EVT cells. The stimulatory effects of GDF-8 on Snail and Slug expression were blocked by pretreatment of SB431542 and siRNA-mediated knockdown of SMAD4. Interestingly, using the siRNA knockdown approach, our results showed that Snail but not Slug was required for the GDF-8-induced MMP2 expression and cell invasion in HTR-8/SVneo cells. The reduction of MMP2 expression in the placentas with preeclampsia (PE) was also observed. Conclusions These findings discover the physiological function of GDF-8 in the human placenta and provide important insights into the regulation of MMP2 expression in human EVT cells.

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Section: Introductionmentioning

confidence: 99%

Snail mediates GDF-8-stimulated human extravillous trophoblast cell invasion by upregulating MMP2 expression

et al. 2023

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“…This involves the exchange of nutrients and waste materials across the feto-placental unit. Trophoblast cells are transiently invasive [ 35 , 36 ] and participate in the remodeling of the maternal uterine matrix and its vasculature to gain access to its nutrient-rich milieu. Successful pregnancy depends on the efficiency of this process, which depends on an efficient trophoblast differentiation program.…”

Section: Introductionmentioning

confidence: 99%

Monosodium Glutamate Perturbs Human Trophoblast Invasion and Differentiation through a Reactive Oxygen Species-Mediated Pathway: An In-Vitro Assessment

et al. 2023

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The overproduction of reactive oxygen species (ROS) has been associated with various human diseases. ROS exert a multitude of biological effects with both physiological and pathological consequences. Monosodium glutamate (MSG), a sodium salt of the natural amino acid glutamate, is a flavor-enhancing food additive, which is widely used in Asian cuisine and is an ingredient that brings out the “umami” meat flavor. MSG consumption in rats is associated with ROS generation. Owing to its consumption as part of the fast-food culture and concerns about its possible effects on pregnancy, we aimed to study the impact of MSG on placental trophoblast cells. MSG exposure influenced trophoblast invasion and differentiation, two of the most critical functions during placentation through enhanced production of ROS. Similar findings were also observed on MSG-treated placental explants, as confirmed by elevated Nrf2 levels. Ultrastructural studies revealed signs of subcellular injury by MSG exposure. Mechanistically, MSG-induced oxidative stress with endoplasmic reticulum stress pathways involving Xbp1s and IRE1α was observed. The effect of MSG through an increased ROS production indicates that its long-term exposure might have adverse health effect by compromising key trophoblast functions.

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“…This also involves the exchange of nutrients and waste across the feto-placental unit. Trophoblast cells are pseudo-malignant 28 and transiently invasive 29 , participating in remodeling the maternal uterine matrix and its vasculature to gain access to its nutrient-rich milieu. Successful pregnancy depends on how e ciently this process is accomplished.…”

Section: Introductionmentioning

confidence: 99%

Monosodium glutamate (MSG) perturbs trophoblast differentiation and invasion program through a ROS-mediated pathway

Mukherjee¹,

Singh

Biswas³

et al. 2022

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Monosodium glutamate (MSG) is a flavor-enhancing food additive widely used in Asian cuisine. It is one of the common ingredients used in curry and other tinned food that is believed to bring out the "umami" meat flavor and enhance the savory taste of the food. It is the sodium salt of the naturally occurring amino acid Glutamate. Due to its massive consumption as part of fast-food culture along with concerns about its possible effect on health in general and pregnancy in particular, we undertook this study to address its impact on placental trophoblast cells. We investigated the effect of MSG on placental trophoblast cells. Our studies confirmed that short and long-term exposure to MSG has a profound influence on trophoblast invasion and differentiation, two of the most critical and dispensable functions during placentation. Our results showed an acute short-term MSG-treatment enhanced trophoblast invasion and cell motility along with an increased expression in trophoblast cell differentiation markers. However, long-term chronic MSG stimulation in these cell types showed the opposite effect with both reduced invasion and differentiation. Further, MSG-treated placental explants displayed signs of elevated oxidative stress. These effect of MSG on trophoblast cells along with an increased ROS production indicates that long-term usage of MSG as part of food additive might have adverse health consequences on the developing embryo by compromising the trophoblast and placental function.

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MTiness in pseudo-malignant behavior of trophoblasts during embryo implantation

Cited by 6 publications

References 85 publications

Snail mediates GDF-8-stimulated human extravillous trophoblast cell invasion by upregulating MMP2 expression

Snail mediates GDF-8-stimulated human extravillous trophoblast cell invasion by upregulating MMP2 expression

Monosodium Glutamate Perturbs Human Trophoblast Invasion and Differentiation through a Reactive Oxygen Species-Mediated Pathway: An In-Vitro Assessment

Monosodium glutamate (MSG) perturbs trophoblast differentiation and invasion program through a ROS-mediated pathway

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