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![Evaluation of the Sdc-1 kd in the human EnS cell lines. (a) Sdc-1 mRNA levels determined by QGP assay [MFI = mean fluorescence intensity], the qualitative Sdc-1 protein expression was determined by dot blot analysis depicted in (b) and the corresponding pixel density evaluation is shown in (c) with and without decidualization (+/−d) and with and without inducing the Sdc-1 kd (+/−Tet) in KdS1 cells with 1 μg/mL Tet. The dot blot analysis was performed with 30 μg protein per dot, and samples were applied in the same order as in (c). Data represent means ± SD with p∗<0.05 for Tet treated KdS1 cells versus untreated KdS1 (+/−d) cells.](publication/313816294/figure/fig3/AS:1086530223382563@1636060400434/Evaluation-of-the-Sdc-1-kd-in-the-human-EnS-cell-lines-a-Sdc-1-mRNA-levels-determined.jpg)
Evaluation of the Sdc-1 kd in the human EnS cell lines. (a) Sdc-1 mRNA levels determined by QGP assay [MFI = mean fluorescence intensity], the qualitative Sdc-1 protein expression was determined by dot blot analysis depicted in (b) and the corresponding pixel density evaluation is shown in (c) with and without decidualization (+/−d) and with and without inducing the Sdc-1 kd (+/−Tet) in KdS1 cells with 1 μg/mL Tet. The dot blot analysis was performed with 30 μg protein per dot, and samples were applied in the same order as in (c). Data represent means ± SD with p∗<0.05 for Tet treated KdS1 cells versus untreated KdS1 (+/−d) cells.
Source publication
Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif li...
Citations
... Due to reduced trophoblast invasion and aberrant vascular remodeling, it may prolong placental oxidative stress, which in turn may exacerbate the dysfunction of trophoblasts that is a defining feature of PE (Anton et al., 2013;Fu et al., 2013). The research also demonstrated that IL-1β induces CXCL1 expression, which aids trophoblast invasion (Baston-buest et al., 2017). In addition, microRNAs (miRNAs) are small, non-coding, singlestranded RNA that regulate gene expression at the posttranscriptional and transcriptional levels to a lesser extent (O 'Brien et al., 2018). ...
Diabetes-related pathophysiological alterations and various female reproductive difficulties were common in pregnant women with gestational diabetes mellitus (GDM), who had 21.1 million live births. Preeclampsia (PE), which increases maternal and fetal morbidity and mortality, affects approximately 3%–5% of pregnancies worldwide. Nevertheless, it is unclear what triggers PE and GDM to develop. Therefore, the development of novel moderator therapy approaches is a crucial advancement. Chemokines regulate physiological defenses and maternal-fetal interaction during healthy and disturbed pregnancies. Chemokines regulate immunity, stem cell trafficking, anti-angiogenesis, and cell attraction. CXC chemokines are usually inflammatory and contribute to numerous reproductive disorders. Fractalkine (CX3CL1) may be membrane-bound or soluble. CX3CL1 aids cell survival during homeostasis and inflammation. Evidence reveals that CXC and CX3CL1 chemokines and their receptors have been the focus of therapeutic discoveries for clinical intervention due to their considerable participation in numerous biological processes. This review aims to give an overview of the functions of CXC and CX3CL1 chemokines and their receptors in the pathophysiology of PE and GDM. Finally, we examined stimulus specificity for CXC and CX3CL1 chemokine expression and synthesis in PE and GDM and preclinical and clinical trials of CXC-based PE and GDM therapies.
... Syndecan-1 (SDC1) is the co-receptor of CXCL1, a chemokine that plays a key role in embryonic implantation. SDC1 regulates CXCL1 expression and trophoblast invasion into the endometrium during the peri-implantation period [44]. As a member of the lysosomal-associated protein transmembrane (LAPTM) family, LAPTM4B affect membrane properties of EVs by regulating lipid composition [45]. ...
Background
Studies have shown that sperm-borne microRNAs (miRNAs) are involved in mammalian preimplantation embryonic development. In humans, spermatozoan miR-34c levels are correlated with in vitro fertilization outcomes, such as embryo quality and the clinical pregnancy and live birth rates. In rabbits and cows, miR-34c improves the developmental competence of embryos generated by somatic cell nuclear transfer. However, the mechanisms underlying the regulation of embryonic development by miR-34c remain unknown.
Methods
Female C57BL/6 mice (6–8 weeks old) were superovulated, and pronucleated zygotes were collected and microinjected with an miR-34c inhibitor or a negative-control RNA. The embryonic development of the microinjected zygotes was evaluated, and the messenger RNA (mRNA) expression profiles of the embryos at the two-cell, four-cell and blastocyst stages (five embryos per group) were determined by RNA sequencing analysis. Gene expression levels were verified by reverse transcription–quantitative polymerase chain reaction. Cluster analysis and heat map visualization were performed to detect differentially expressed mRNAs. Pathway and process enrichment analyses were performed using ontology resources. Differentially expressed mRNAs were systematically analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins database to determine their biological functions.
Results
Embryonic developmental potential was significantly reduced in zygotes microinjected with the miR-34c inhibitor compared with those microinjected with a negative-control RNA. Two-cell stage embryos microinjected with an miR-34c inhibitor presented altered transcriptomic profiles, with upregulated expression of maternal miR-34c target mRNAs and classical maternal mRNAs. Differentially expressed transcripts were mainly of genes associated with lipid metabolism and cellular membrane function at the two-cell stage, with cell-cycle phase transition and energy metabolism at the four-cell stage; and with vesicle organization, lipid biosynthetic process and endomembrane system organization at the blastocyst stage. We also showed that genes related to preimplantation embryonic development, including Alkbh4, Sp1, Mapk14, Sin3a, Sdc1 and Laptm4b, were significantly downregulated after microinjection of an miR-34c inhibitor.
Conclusions
Sperm-borne miR-34c may regulate preimplantation embryonic development by affecting multiple biological processes, such as maternal mRNA degradation, cellular metabolism, cell proliferation and blastocyst implantation. Our data demonstrate the importance of sperm-derived miRNAs in the development of preimplantation embryos.
... Syndecan-1 has its predominant expression in the placenta among all human tissues [62]. It is highly expressed in the glycocalyx, covering the chorionic villi of the human placenta [38,39,41,63], where it plays an important anticoagulant role and is involved in the regulation of cell functions in physiologic pregnancies [40,41,[64][65][66]. Previous studies examined the potential value of maternal plasma syndecan-1 as a biomarker for adverse pregnancy outcomes [67]. ...
Objective
The identification of fetal growth disorders is an important clinical priority given that they increase the risk of perinatal morbidity and mortality as well as long-term diseases. A subset of small-for-gestational-age (SGA) infants are growth-restricted, and this condition is often attributed to placental insufficiency. Syndecan-1, a product of the degradation of the endothelial glycocalyx, has been proposed as a biomarker of endothelial damage in different pathologies. During pregnancy, a “specialized” form of the glycocalyx—the “syncytiotrophoblast glycocalyx”—covers the placental villi. The purpose of this study was to determine whether the concentration of maternal plasma syndecan-1 can be proposed as a biomarker for fetal growth restriction.
Study design
A cross-sectional study was designed to include women with normal pregnancy (n = 130) and pregnant women who delivered an SGA neonate (n = 50). Doppler velocimetry of the uterine and umbilical arteries was performed in women with an SGA fetus at the time of diagnosis. Venipuncture was performed within 48 h of Doppler velocimetry and plasma concentrations of syndecan-1 were determined by a specific and sensitive immunoassay.
Results
(1) Plasma syndecan-1 concentration followed a nonlinear increase with gestational age in uncomplicated pregnancies (R² = 0.27, p < .001); (2) women with a pregnancy complicated with an SGA fetus had a significantly lower mean plasma concentration of syndecan-1 than those with an appropriate-for-gestational-age fetus (p = .0001); (3) this difference can be attributed to fetal growth restriction, as the mean plasma syndecan-1 concentration was significantly lower only in the group of women with an SGA fetus who had abnormal umbilical and uterine artery Doppler velocimetry compared to controls (p = .00071; adjusted p = .0028). A trend toward lower syndecan-1 concentrations was also noted for SGA with abnormal uterine but normal umbilical artery Doppler velocimetry (p = .0505; adjusted p = .067); 4) among women with an SGA fetus, those with abnormal umbilical and uterine artery Doppler findings had a lower mean plasma syndecan-1 concentration than women with normal Doppler velocimetry (p = .02; adjusted p = .04); 5) an inverse relationship was found between the maternal plasma syndecan-1 concentration and the umbilical artery pulsatility index (r = −0.5; p = .003); and 6) a plasma syndecan-1 concentration ≤ 850 ng/mL had a positive likelihood ratio of 4.4 and a negative likelihood ratio of 0.24 for the identification of a mother with an SGA fetus who had abnormal umbilical artery Doppler velocimetry (area under the ROC curve 0.83; p < .001).
Conclusion
Low maternal plasma syndecan-1 may reflect placental diseases and this protein could be a biomarker for fetal growth restriction. However, as a sole biomarker for this condition, its accuracy is low.
... Syndecans, including the syndecan-1 (SDC-1) primarily seen on the epithelial cells, constitute a family of transmembrane heparan sulfate proteoglycans consisting of four members, differing from each other based on their highly variable extracellular domains [15]. During pregnancy, SDC-1 seemingly affects cell signaling and intercellular interaction at the trophoblast-decidual interface [16]. While usually present on the cell surface, the ectodomains of these proteoglycans can be shed from the cell surface, generating soluble molecules that can inhibit interactions at the cell surface [17]. ...
Exploration of novel biomarkers has been gaining popularity in preeclampsia, which is currently being diagnosed based on clinical criteria alone. Soluble syndecan-1, released from one of the proteoglycans associated with the syncytiotrophoblastic layer of the placenta, is affected in patients with abnormal placentation. This article is the first systematic literature review that evaluates the relationship between the antepartum serum levels of the syndecan-1 and preeclampsia. Eight studies were selected after screening and quality appraisal, and data were analyzed. The serum concentration of syndecan-1 was found to correlate positively with the gestational age in all pregnancies and negatively with the systolic blood pressure in patients with preeclampsia. Extremely low levels of soluble syndecan-1 may be helpful as a predictor for the development of preeclampsia during gestation.
... Immune cells secrete and communicate through chemokines such as CXCL1 which acts via its receptors CXCR2 and SDC-1. Our previous study has shown how SDC-1 functions as an important regulator of CXCL1 expression in endometrial stroma cells (Baston-Buest et al., 2017). In the present study, which is composed of infertility patients, we found high immunoreactivity of CXCL1 in all compartments of the endometrium, with equally intense staining in all specimen. ...
There is growing evidence that changes in the eutopic endometrial immune profile are a cause of endometriosis-associated infertility. Women affected by endometriosis experience a 2-fold increased risk of infertility compared to healthy controls. In our study we aimed to map out endometrial expressions of uterine natural killer cells, plasma cells, macrophages and the chemokine CXC-motif ligand 1 (CXCL1) as well as its main receptors CXC-motif receptor 2 (CXCR2) and Syndecan-1 in infertility-patients with endometriosis. 36 infertility patients were included of which 19 suffered from endometriosis and 17 served as a control cohort. All patients underwent endometrial scratching in the secretory phase and immunohistochemical staining which was evaluated by three independent observers. In endometriosis-patients, a higher concentration of macrophages coincided with an elevated number of uterine natural killer cells or plasma cells. Patients with endometriosis also showed a higher endothelial expression of VEGF-A. Furthermore, absence of stromal expression of SDC-1 was associated with an elevated level of uNK in general. Therefore, our study links endometriosis to an altered immune cell population in the eutopic endometrium, which might be a new approach to diagnosing endometriosis in infertility patients.
... CXCL1, also a chemokine, is secreted by trophoblasts and has been shown to play a role in the recruitment of regulatory T-cells needed for maternal tolerance of the fetus [36], as well as having an angiogenic role [28]. CXCL1 expression was also shown to be induced by IL1B and to promote trophoblast invasion [37]. ...
... HTR8/SVneo cells transfected with miR-210-3p mimics ( Figure 4A) showed a significant decrease in key markers, ITGA1 and PECAM1, but no significant change in CDH5 and HLA-G was observed. Moreover, miR-210-3p also significantly decreased mRNA levels of the proinflammatory cytokine IL1B and chemokines CXCL8 and CXCL1, all of which have been shown to be important for trophoblast invasion and in the recruitment of immune cells to remodeling spiral arteries [27,34,37,38]. However, downregulation of endogenous miR-210-3p by anti-miR-210-3p showed no significant effects on the mRNA level of all of these markers ( Figure 4B). ...
... HTR8/SVneo cells transfected with miR-210-3p mimics ( Figure 4A) showed a significant decrease in key markers, ITGA1 and PECAM1, but no significant change in CDH5 and HLA-G was observed. Moreover, miR-210-3p also significantly decreased mRNA levels of the pro-inflammatory cytokine IL1B and chemokines CXCL8 and CXCL1, all of which have been shown to be important for trophoblast invasion and in the recruitment of immune cells to remodeling spiral arteries [27,34,37,38]. However, downregulation of endogenous miR-210-3p by anti-miR-210-3p showed no significant effects on the mRNA level of all of these markers ( Figure 4B). ...
Hsa-miR-210-3p has been reported to be upregulated in preeclampsia (PE); however, the functions of miR-210-3p in placental development are not fully understood, and, consequently, miR-210-3p’s role in the pathogenesis of PE is still under investigation. In this study, we found that overexpression of miR-210-3p reduced trophoblast migration and invasion, extravillous trophoblast (EVT) outgrowth in first trimester explants, expression of endovascular trophoblast (enEVT) markers and the ability of trophoblast to form endothelial-like networks. In addition, miR-210-3p overexpression significantly downregulated the mRNA levels of interleukin-1B and -8, as well as CXC motif ligand 1. These cytokines have been suggested to play a role in EVT invasion and the recruitment of immune cells to the spiral artery remodeling sites. We also showed that caudal-related homeobox transcription factor 2 (CDX2) is targeted by miR-210-3p and that CDX2 downregulation mimicked the observed effects of miR-210-3p upregulation in trophoblasts. These findings suggest that miR-210-3p may play a role in regulating events associated with enEVT functions and its overexpression could impair spiral artery remodeling, thereby contributing to PE.
... Por otra parte, los Sdcs se expresan en la superficie de células adherentes y no adherentes, sirviendo como correceptores para diversos ligandos, como factores de crecimiento, proteasas, inhibidores de proteasa, quimiocinas y citoquinas que intervienen en múltiples procesos fisiológicos y/o patológicos, incluída la regulación de proteínas del citoesqueleto. Todo esto le otorga un papel importante en la invasión celular, por lo que Sdc-1 podría actuar como un marcador de diagnóstico para la falla o trastorno de la implantación (Baston-Buest et al., 2017). ...
PRIETO, G. R.; VIDAL, S. N. E.; LIZAMA, P. R. A.; MIRANDA, K. R. E.; NAHUELCURA, M. N. E.; ORTEGA, S. M. E.; OTTONE, N. E. & DEPPE, A. M. Interacción endometrio trofoblasto, en la implantación humana: Revisión de la literatura. Int. J. Morphol., 37(2):397-405, 2019. RESUMEN: Un embarazo exitoso requiere de una serie de interacciones mediadas por factores hormonales, moleculares y fenómenos de inmunomodulación. Una de estas interacciones es la que ocurre entre el endometrio y el blastocito, previo y durante el proceso de implantación. El objetivo de esta revisión bibliográfica es complementar lo descrito en la literatura clásica de embriología humana sobre interacción de endometrio-blastocito. La búsqueda bibliográfica se realizó en la base de datos MEDLINE usando los términos en inglés "implantation", "endometrium" y "embryo"; además se realizó una búsqueda manual, que incluyó artículos de revis-tas no indexadas, libros de texto y atlas. Se consideraron criterios de inclusión y exclusión para la selección de los artículos y otros recursos bibliográficos. Entre los criterios de inclusión se consideraron estudios realizados en humanos, artículos de revisión y experi-mentación, publicados en los últimos 5 años. Como criterios de exclusión se consideraron artículos que utilizaran animales, estudios sobre fertilidad in vitro, patologías asociadas y artículos no relacionados al tema. Una vez completada la selección, se examinaron los textos completos, en los cuales se aplicaron nuevamente los criterios de exclusión. La búsqueda arrojó un total de 560 artículos, cuyo análisis de los títulos y resúmenes resultó en 475 trabajos excluidos, a partir de los diferentes criterios de exclusión antes descritos. Por lo tanto, se obtuvieron 85 artículos, en los cuales se realizó el análisis del texto completo. De estos artículos, se obtuvieron un total de 34 estudios y los contenidos seleccionados en esta revisión fueron: Endometrio, Interacción endometrio trofoblasto, Aposición, Adhesión y Migración-Invasión. Durante la implantación se genera una interacción entre el endometrio y el trofoblasto, con la participación de moléculas reguladoras de proliferación y diferenciación, como factores hormonales, moleculares y de expresión génica. Sin embargo, los mecanismos específicos de acción e interacción deben continuar siendo investigados, para responder interrogantes en el ámbito del crecimiento y desarrollo humano.
... Por otra parte, los Sdcs se expresan en la superficie de células adherentes y no adherentes, sirviendo como correceptores para diversos ligandos, como factores de crecimiento, proteasas, inhibidores de proteasa, quimiocinas y citoquinas que intervienen en múltiples procesos fisiológicos y/o patológicos, incluída la regulación de proteínas del citoesqueleto. Todo esto le otorga un papel importante en la invasión celular, por lo que Sdc-1 podría actuar como un marcador de diagnóstico para la falla o trastorno de la implantación (Baston-Buest et al., 2017). ...
A successful pregnancy requires a series of interactions, mediated by hormonal, molecular and immunomodulation phenomena. One of these interactions is between the endometrium and the blastocyst, before and during the implantation process. The objective of this literature review is to complement what is described in the classic human embryology literature on endometrial-blastocyst interaction. The bibliographic search was carried out in the MEDLINE database using the terms "implantation", "endometrium" and "embryo", and a manual search was carried out, which included articles from non-indexed journals, textbooks and atlases. Inclusion and exclusion criteria were considered for the selection of articles and other bibliographic resources, including human studies, review and experimentation articles, published in the last 5 years. Articles with animals as experimental subjects, in vitro fertility studies, associated pathologies and articles not related to the subject were excluded. When the selection was completed, the complete texts were examined, in which the exclusion criteria were applied again The search yielded a total of 560 articles, whose analysis of titles and abstracts resulted in 475 excluded works, in relation to different exclusion criteria described above. Therefore, 85 articles were obtained, in which the complete text analysis was performed. From these articles, a total of 34 studies were obtained and the contents selected in this review were: Endometrium, Endometrium trophoblast, Aposition, Adhesion and Migration-Invasion. During the implantation, aninteraction between the endometrium and the trophoblast is generated, with the participation of regulatory molecules of proliferation and differentiation, such as hormonal, molecular and gene expression factors. However, the specific mechanisms of action and interaction must continue to be investigated, to answer questions in the field of human growth and development.
... The present study focuses on the reproductive phenotype of heterozygous Sdc1 +/− mice, as studies from our group previously showed the involvement of SDC1 at the embryo-maternal interface in vitro regulating the secretion of chemokines and angiogenic factors during decidualization, implantation and implantation-associated apoptosis in human endometrial epithelial and stromal cells [5][6][7]. SDC1 has been shown to be expressed in the human endometrium throughout the menstrual cycle [8] and could be associated with numerous human pregnancy pathologies based upon an insufficient implantation process. The reduced placental expression of SDC1 could be correlated with intrauterine growth restriction [9], preeclampsia [10], and hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome [11], whereas elevated placental SDC1 expression reduced the risk for preterm birth [12]. ...
Background
Syndecan-1 is a heparan sulfate proteoglycan acting as a co-receptor for cytokines and growth factors mediating developmental, immunological and angiogenic processes. In human, the uteroplacental localization of Syndecan-1 and its reduced expression in pregnancy-associated pathologies, such as the intrauterine growth restriction, suggests an influence of Syndecan-1 in embryo-maternal interactions. The aim of the present study was to identify the effect of a reduced expression of Syndecan-1 on the reproductive phenotype of mice and their progenies.
Methods
Reproductive characteristics have been investigated using animals with reduced Syndecan-1 and their wildtype controls after normal mating and after vice versa embryo transfers. Female mice were used to measure the estrus cycle length and the weight gain during pregnancy, as well as for histological examination of ovaries. Male mice were examined for the concentration, motility, viability and morphology of spermatozoa. Organs like heart, lung, liver, kidney, spleen, brain and ovaries or testes and epididymis of 6-month-old animals were isolated and weighed. Statistical analyses were performed using two-tailed students t-test with P < .05 and P < .02, chi square test (P < .05) and Fisher’s Exact Test (P < .05). A linear and a non-linear mixed-effects model were generated to analyze the weight gain of pregnant females and of the progenies.
Results
Focusing on the pregnancy outcome, the Syndecan-1 reduced females gave birth to larger litters. However, regarding the survival of the offspring, a higher percentage of pups with less Syndecan-1 died during the first postnatal days. Even though the ovaries and the testes of Syndecan-1 reduced mice showed no histological differences and the ovaries showed a similar number of primary and secondary follicles and corpora lutea, the spermatozoa of Syndecan-1 reduced males showed more tail and midpiece deficiencies. Concerning the postnatal and juvenile development the pups with reduced Syndecan-1 expression remained lighter and smaller regardless whether carried by mothers with reduced Syndecan-1 or wildtype foster mothers. With respect to anatomical differences kidneys of both genders as well as testes and epididymis of male mice with reduced syndecan-1 expression weighed less compared to controls.
Conclusions
These data reveal that the effects of Syndecan-1 reduction are rather genotype- than parental-dependent.
... MMP-14 can also participate in the proteolytic processing of other embryonic transmembrane factors including membrane-bound pro-TGF-β, EphA2 receptor (Sugiyama et al., 2013), cell surface tissue transglutaminase (Belkin et al., 2001) and heparin sulfate proteoglycan syndecan-1 (Endo et al., 2003), whose importance in trophoblast implantation and maternal-fetal interaction has been previously suggested (Baston-Buest et al., 2017;Kabir-Salmani et al., 2005;Yang & Min, 2011). However, due to insufficient information about their expression in the trophoblast cells of preimplantation embryo as well as their exact roles in the implantation process, the effect of exosomal MMP-14 on implantation through their shedding is not currently known. ...
During embryo implantation, crosstalk between the endometrial epithelium and the blastocyst, especially the trophoblasts, is a prerequisite for successful implantation. During this crosstalk, various molecular and functional changes occur to promote synchrony between the embryo and the endometrium as well as the uterine cavity microenvironment. In the past few years, growing evidence has shown that endometrium-derived exosomes play pivotal roles in the embryonic-maternal crosstalk during implantation, although the exact mechanism of this crosstalk has yet to be determined. The presence of metalloproteinases has been reported in endometrium-derived exosomes, implying the importance of these enzymes in exosome-based crosstalk. Thus, in this review, we describe the potential roles of the metalloproteinases of endometrium-derived exosomes in promoting embryo attachment and implantation. This study could provide a better understanding of the potential roles of exosomal metalloproteinases in embryo implantation and pave the way for developing novel exosome-based regulatory agents to support early pregnancy. This article is protected by copyright. All rights reserved
