Expression and function of galectins in the endometrium and at the human feto-maternal interface

Jeschke, Udo; Hutter, Stefan; Heublein, Sabine; Vrekoussis, Thomas; Andergassen, Ulrich; Unverdorben, Laura; Papadakis, George; Makrigiannakis, Antonis

doi:10.1016/j.placenta.2013.07.005

Cited by 35 publications

(33 citation statements)

References 161 publications

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“…Supports MUC16-dependent cell adhesion and mesothelial colonization Gubbels et al ( 2006 ) galectins in embryo implantation and placentation, notably galectin-1 [Jeschke et al ( 2013 ) for review]. In addition, elevated galectin-7 expression is associated with uterine repair after menstruation (Evans et al 2014 ), miscarriage (Menkhorst et al 2014b ), and preeclampsia (Menkhorst et al 2014a ).…”

Section: Galectinsmentioning

confidence: 94%

“…Galectins are a family of small (14-39 kDa), soluble, β-galactoside binding proteins that occur both intracellularly and on the cell surface (Jeschke et al 2013 ). Galectins do not have canonical signal sequences or transmembrane domains and reach the cell surface by nonclassical pathways.…”

Section: Galectinsmentioning

confidence: 99%

“…While the presence of β-galactose is required for galectin recognition, other aspects of oligosaccharide structure, e.g., sialylation, presence of lactosamine repeats, create differences in recognition by different galectins changing binding affi nities up to 100-fold (Stowell et al 2008 ;Zhuo et al 2008 ). Multiple galectins have been detected in human endometrium and placental tissues with a wider variety found in placental tissues (Jeschke et al 2013 ). Several galectins can bind to TMs, including MUC1, MUC4, and MUC16 (Bancalari et al 1989 ;Seelenmeyer et al 2003 ;Yu et al 2007 ;Argueso et al 2009 ;Senapati et al 2011 ).…”

Section: Galectinsmentioning

confidence: 99%

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Transmembrane Mucin Expression and Function in Embryo Implantation and Placentation

Constantinou

Morgado

Carson

2015

Advances in Anatomy, Embryology and Cell Biology

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Transmembrane mucins (TMs) are extremely large, complex glycoproteins that line the apical surfaces of simple epithelia including those of the female reproductive tract. TMs provide a physical barrier consistent with their role as part of the innate immune system. This barrier function must be overcome in the context of embryo implantation to permit blastocyst attachment. Three major TMs have been identified in uterine epithelia of multiple species: MUC1, MUC4, and MUC16. MUC1 has been found in all species studied to date, whereas expression of MUC4 and MUC16 have been less well studied and may be species specific. The strategies for removing mucins to permit embryo attachment also vary in a species-specific way and include both hormonal suppression of TM gene expression and membrane clearance via cell surface proteases. Studies emerging from the cancer literature indicate that TMs can modulate a surprisingly wide variety of signal transduction processes. Furthermore, various cell surface proteins have been identified that bind either the oligosaccharide or protein motifs of TMs suggesting that these molecules may support cell attachment in some contexts, including trophoblast interactions with cells of the immune system. The intimate association of TMs at sites of embryo-maternal interaction and the varied functions these complex molecules can play make them key players in embryo implantation and placentation processes.

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Section: Galectinsmentioning

confidence: 94%

Section: Galectinsmentioning

confidence: 99%

Section: Galectinsmentioning

confidence: 99%

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Transmembrane Mucin Expression and Function in Embryo Implantation and Placentation

Constantinou

Morgado

Carson

2015

Advances in Anatomy, Embryology and Cell Biology

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“…396,397,398,399 Whereas exosomes are found in the circulation of pregnant women, little is known about trophoblastic exosomes, and many studies on extracellular vesicles in pregnancy have associated a mixture of vesicles (exosomes, MVs, ABs) with disorders of pregnancy, thus blurring some the distinct properties of these vesicles. 400,401,402,403,404 Placental exosomes have been implicated in several discrete functions, such as immune modulation, 405,406,407 where exosomal cargo proteins, such as galectin-3 408 and HLA-G 409 , may perform an immune modulatory function. 410 Other exosomal cargo molecules, such as Wnt/β-catenin, fibronectin, and prostaglandins, may play a role in supporting homeostasis throughout pregnancy.…”

Section: Evolving Technologies For Placental Specific Therapeuticmentioning

confidence: 99%

Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

Ilekis

Tsilou

Fisher

et al. 2016

American Journal of Obstetrics and Gynecology

237

167

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Although much progress is being made in understanding the molecular pathways in the placenta involved in the pathophysiology of pregnancy related disorders, a significant gap exists in utilizing this information for developing new drug therapies to improve pregnancy outcome. On March 5–6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a two day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given in the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of this workshop. A broad number of topics were covered ranging from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and non-infectious agents. Research findings in these areas will be critical for formulating developing future treatments and developing therapies for the prevention of a number of pregnancy disorders of placental origin including preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented summarizing ongoing clinical efforts in the U.S. and in Europe testing novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy using virally-delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by enhancing nutrient transport to the fetus by modulating their placental transporters, as well as targeting placental mitochondrial dysfunction and oxidative stress to improve placental health. The roles of microRNAs and placental-derived exosomes, as well as messenger RNAs, were also discussed in the context of their use for diagnostics and as drug targets. The workshop discussed the aspect of safety and pharmacokinetic profiles of potential existing and new therapeutics that will need to be determined especially in the context of the unique pharmacokinetic properties of pregnancy, as well as the hurdles and pitfalls of translating research findings into practice. The workshop also discussed novel methods of drug delivery and targeting during pregnancy using macromolecular carriers, such as nanoparticles and biopolymers, to minimize placental drug transfer and hence fetal drug exposure. In closing, a major theme that developed from the workshop was that the scientific community needs to change their thinking of the pregnant women and her fetus as a vulnerable patient population for which drug development should be avoided, but rather thought of as a deprived population in need of more effective therapeutic interventions.

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“…Galectin-13 and placental Chr19 cluster galectins are predominantly expressed by the syncytiotrophoblast [30,31,33–35,44–46], a multinucleated syncytium that is in direct contact with maternal immune cells in maternal blood [30,31,34,35,43–45,47]. This cell layer is generated by the categorical reprogramming of the trophoblastic transcriptional program mainly governed by cAMP, and the consequent biochemical and morphological differentiation and fusion of the underlining villous cytotrophoblasts into this syncytium [45,47–54].…”

Section: Introductionmentioning

confidence: 99%

Evolutionary origins of the placental expression of chromosome 19 cluster galectins and their complex dysregulation in preeclampsia

Than¹,

Romero²,

Xu³

et al. 2014

Placenta

135

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Introduction The dysregulation of maternal-fetal immune tolerance is one of the proposed mechanisms leading to preeclampsia. Galectins are key regulator proteins of the immune response in vertebrates and maternal-fetal immune tolerance in eutherian mammals. Previously we found that three genes in a Chr19 cluster encoding for human placental galectin-13 (PP13), galectin-14 and galectin-16 emerged during primate evolution and may confer immune tolerance to the semi-allogeneic fetus. Materials and Methods This study involved various methodologies for gene and protein expression profiling, genomic DNA methylation analyses, functional assays on differentiating trophoblasts including gene silencing, luciferase reporter and methylation assays. These methods were applied on placental specimens, umbilical cord blood cells, primary trophoblasts and BeWo cells. Genomic DNA sequences were analyzed for transposable elements, transcription factor binding sites and evolutionary conservation. Results and Discussion The villous trophoblastic expression of Chr19 cluster galectin genes is developmentally regulated by DNA methylation and induced by key transcription factors of villous placental development during trophoblast fusion and differentiation. This latter mechanism arose via the co-option of binding sites for these transcription factors through promoter evolution and the insertion of an anthropoid-specific L1PREC2 transposable element into the 5’ untranslated region of an ancestral gene followed by gene duplication events. Among placental Chr19 cluster galectin genes, the expression of LGALS13 and LGALS14 is down-regulated in preterm severe preeclampsia associated with SGA. We reveal that this phenomenon is partly originated from the dysregulated expression of key transcription factors controlling trophoblastic functions and galectin gene expression. In addition, the differential DNA methylation of these genes was also observed in preterm preeclampsia irrespective of SGA. Conclusions These findings reveal the evolutionary origins of the placental expression of Chr19 cluster galectins. The complex dysregulation of these genes in preeclampsia may alter immune tolerance mechanisms at the maternal-fetal interface.

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Expression and function of galectins in the endometrium and at the human feto-maternal interface

Cited by 35 publications

References 161 publications

Transmembrane Mucin Expression and Function in Embryo Implantation and Placentation

Transmembrane Mucin Expression and Function in Embryo Implantation and Placentation

Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

Evolutionary origins of the placental expression of chromosome 19 cluster galectins and their complex dysregulation in preeclampsia

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