Role for the endometrial epithelial protein MFG-E8 and its receptor integrin αvβ3 in human implantation: results of an in vitro trophoblast attachment study using established human cell lines

Schmitz, Carlos André Aita; Yu, Lian; Bocca, Silvina; Anderson, Sandra D.; Cunha-Filho, João Sabino; Rhavi, Bhaskara S.; Oehninger, Sergio

doi:10.1016/j.fertnstert.2013.12.015

Cited by 30 publications

(30 citation statements)

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“…Our data showed that MFGE8 protein is upregulated by prolactin in primary endometrial epithelial cell cultures, indicating paracrine epithelial-stromal cells interaction (Franchi et al 2011). In addition, MFGE8 protein is highly expressed in human chorionic villi at all trimesters of gestation and in murine implantation sites (Bocca et al 2012), and participates in trophoblast adhesion with its receptor integrin ανβ3 in an in vitro model of human implantation (Schmitz et al 2014). We have also demonstrated that endometrial MFGE8 gene expression, as well as the expression of other inflammatory factors, such as are significantly regulated by TNFα and hCG (Sarhan A et al 2013) respectively.…”

Section: Introductionsupporting

confidence: 58%

“…We herein explored EMT of endometrial epithelial cells and their modifications in morphology and motility during the early stages of embryonic and endometrial epithelial cells interaction. MFGE8 has demonstrated functions in cell remodeling in breast cancer progression (Yang et al 2011), and participates in immunomodulation and cell adhesion in the endometrium (Schmitz et al 2014). In addition, findings in human melanoma cells revealed the promotion effects of MFGE8 on EMT in tumor microenvironment, where MFGE8 augmented cell resistance to apoptosis and stimulated invasion and immune suppression; they also found that MFGE8 knockdown attenuated Akt and Twist signaling and thereby compromised tumor cell survival and invasive ability (Jinushi et al 2008).…”

Section: Discussionmentioning

confidence: 99%

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MFGE8 regulates TGF-β-induced epithelial mesenchymal transition in endometrial epithelial cells in vitro

Sullivan

et al. 2016

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This study investigated the role of milk fat globule-epidermal growth factor-factor 8 (MFGE8) in TGF-β-induced epithelialmesenchymal transition (EMT) of endometrial epithelial cells. These were in vitro studies using human endometrial epithelial cells and mouse blastocysts. We investigated the ability of TGF-β to induce EMT in endometrial epithelial cells (HEC-1A) by assessment of cytological phenotype (by light and atomic force microscopy), changes in expression of the markers of cell adhesion/differentiation E-and N-cadherin, and of the transcription factor Snail (by immunofluorescence and immunoblotting), and competence to support embryo attachment in a mouse blastocyst outgrowth assay. We also studied the effects of E-cadherin

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Section: Introductionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

MFGE8 regulates TGF-β-induced epithelial mesenchymal transition in endometrial epithelial cells in vitro

Sullivan

et al. 2016

Reproduction

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“…It may be that there is a complex interplay between integrins and other cell surface factors. Indeed, a number of components of the uterine cell surface have functional roles in implantation and interact with αv integrins, including CD98 (officially known as SLC3A2) (Domínguez et al, 2010), the tetraspanin CD9 (Domínguez et al, 2010;Liu et al, 2006;Wynne et al, 2006), the dipeptidyl peptidase CD26 (officially known as DPP4) (Shimomura et al, 2006), the epidermal growth factor (EGF)-domaincontaining glycoprotein MFG-E8 (Schmitz et al, 2014), the IGF receptor (Fujita et al, 2013;Kang et al, 2015), galectin 3 (Lei et al, 2009;Yang et al, 2012) and galectin 15 (Lewis et al, 2007).…”

Section: Box 2: Demonstrating Integrin Function In Implantationmentioning

confidence: 99%

Embryo–epithelium interactions during implantation at a glance

Aplin

Ruane

2017

Journal of Cell Science

191

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At implantation, with the acquisition of a receptive phenotype in the uterine epithelium, an initial tenuous attachment of embryonic trophectoderm initiates reorganisation of epithelial polarity to enable stable embryo attachment and the differentiation of invasive trophoblasts. In this Cell Science at a Glance article, we describe cellular and molecular events during the epithelial phase of implantation in rodent, drawing on morphological studies both in vivo and in vitro, and genetic models. Evidence is emerging for a repertoire of transcription factors downstream of the master steroidal regulators estrogen and progesterone that coordinate alterations in epithelial polarity, delivery of signals to the stroma and epithelial cell death or displacement. We discuss what is known of the cell interactions that occur during implantation, before considering specific adhesion molecules. We compare the rodent data with our much more limited knowledge of the human system, where direct mechanistic evidence is hard to obtain. In the accompanying poster, we represent the embryo-epithelium interactions in humans and laboratory rodents, highlighting similarities and differences, as well as depict some of the key cell biological events that enable interstitial implantation to occur.

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“…Researchers observed three fold increament in expression of MFG-E8 during implantation period [22,23]. Schmitz et al [24] observed decreased trophoblast attachment by blocking of MFG-E8 on endometrial cell line in an invitro study. Bocca et al [6] observed expression of MFG-E8 on human placenta at all trimesters of gestation.…”

Section: Are There Any Differences Between Preeclamptic and Healty Prmentioning

confidence: 99%

Untitled

2017

OGIJ

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This prospective, cross-sectional study was conducted with 90 pregnant women who were hospitalized at Firat University Hospital, Department of Gynecology and Obstetrics between December 2013 and December 2015 after local ethics committee approval (Decision No: 06/2013). The study population was consisted of 40 preeclampsia pregnant women (study group) and 50 healthy, gestational age matched pregnant women without previous history of PE (control group AbstractPurpose: Preeclampsia (PE) is closely associated with systemic inflammatory response. Milk Fat Globule Epidermal Growth Factor-8 (MFG-E8), an endometrial epithelial protein, regulates inflammation and apoptosis. Suppressor of cytokine signaling-3 (SOCS-3) plays role on prevention of inflammation. We evaluated the serum and placenta levels of MFG-E8 and SOCS-3 in preeclampsia and healthy pregnant women. Methods:The study population was consisted of 40 preeclampsia and 50 healthy, gestational-age matched women with no history of preeclampsia. Prepartum serum and postpartum placental tissue samples were collected. Serum and placenta MFG-E8 and SOCS-3 levels were analysed with enzyme-linked immuno sorbent assay method. Results:In preeclamptic group, serum MFG-E8 levels raised and showed statistically significant difference with respect to control group (p<0.01). Placental SOCS-3 levels were significantly high in preeclamptic group compared to that in control group. Serum MFG-E8 levels showed positive correlation with both of blood pressure and proteinuria level. Conclusions:In our study, serum MFG-E8 level showed close relation with blood pressure and proteinuria. Increased placental SOCS-3 levels might be the result of compensatory angiogenic and anti-inflammatory response in PE. New studies with expanded populations and genetic evaluations are needed to discuss our results.

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Role for the endometrial epithelial protein MFG-E8 and its receptor integrin αvβ3 in human implantation: results of an in vitro trophoblast attachment study using established human cell lines

Cited by 30 publications

References 54 publications

MFGE8 regulates TGF-β-induced epithelial mesenchymal transition in endometrial epithelial cells in vitro

MFGE8 regulates TGF-β-induced epithelial mesenchymal transition in endometrial epithelial cells in vitro

Embryo–epithelium interactions during implantation at a glance

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