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International Journal of Molecular... Dec 2021Galectins are a family of conserved soluble proteins defined by an affinity for β-galactoside structures present on various glycoconjugates. Over the past few decades,... (Review)
Review
Galectins are a family of conserved soluble proteins defined by an affinity for β-galactoside structures present on various glycoconjugates. Over the past few decades, galectins have been recognized as important factors for successful implantation and maintenance of pregnancy. An increasing number of studies have demonstrated their involvement in trophoblast cell function and placental development. In addition, several lines of evidence suggest their important roles in feto-maternal immune tolerance regulation and angiogenesis. Changed or dysregulated galectin expression is also described in pregnancy-related disorders. Although the data regarding galectins' clinical relevance are still at an early stage, evidence suggests that some galectin family members are promising candidates for better understanding pregnancy-related pathologies, as well as predicting biomarkers. In this review, we aim to summarize current knowledge of galectins in early pregnancy as well as in pregnancy-related pathologies.
Topics: Animals; Female; Galectins; Humans; Placenta; Placentation; Pregnancy; Pregnancy Complications; Trophoblasts
PubMed: 35008499
DOI: 10.3390/ijms23010069 -
Prostaglandins, Leukotrienes, and... Apr 2020Fatty acids are essential for feto-placental growth and development. Maternal fatty acids and their metabolites are involved in every stage of pregnancy by supporting... (Review)
Review
Fatty acids are essential for feto-placental growth and development. Maternal fatty acids and their metabolites are involved in every stage of pregnancy by supporting cell growth and development, cell signaling, and modulating other critical aspects of structural and functional processes. Early placentation process is critical for placental growth and function. Several fatty acids modulate angiogenesis as observed by increased tube formation and secretion of angiogenic growth factors in first-trimester human placental trophoblasts. Long-chain fatty acids stimulate angiogenesis in these cells via vascular endothelium growth factor (VEGF), angiopoietin-like protein 4 (ANGPTL4), fatty acid-binding proteins (FABPs), or eicosanoids. Inadequate placental angiogenesis and trophoblast invasion of the maternal decidua and uterine spiral arterioles leads to structural and functional deficiency of placenta, which contributes to preeclampsia, pre-term intrauterine growth restriction, and spontaneous abortion and also affects overall fetal growth and development. During the third trimester of pregnancy, placental preferential transport of maternal plasma long-chain polyunsaturated fatty acids is of critical importance for fetal growth and development. Fatty acids cross the placental microvillous and basal membranes by mainly via plasma membrane fatty acid transport system (FAT, FATP, p-FABPpm, & FFARs) and cytoplasmic FABPs. Besides, a member of the major facilitator superfamily-MFSD2a, present in the placenta is involved in the supply of DHA to the fetus. Maternal factors such as diet, obesity, endocrine, inflammation can modulate the expression and activity of the placental fatty acid transport activity and thereby impact feto-placental growth and development. In this review, we discuss the maternal dietary fatty acids, and placental transport and metabolism, and their roles in placental growth and development.
Topics: Angiopoietin-Like Protein 4; Cell Membrane; Dietary Fats; Fatty Acid-Binding Proteins; Fatty Acids; Female; Fetal Development; Humans; Neovascularization, Physiologic; Placenta; Placentation; Pregnancy; Pregnancy Trimesters; Trophoblasts; Vascular Endothelial Growth Factor A
PubMed: 32120190
DOI: 10.1016/j.plefa.2020.102080 -
Scientific Reports Mar 2022Placental function requires organized growth, transmission of nutrients, and an anti-inflammatory milieu between the maternal and fetal interface, but placental factors...
Placental function requires organized growth, transmission of nutrients, and an anti-inflammatory milieu between the maternal and fetal interface, but placental factors important for its function remain unclear. Renalase is a pro-survival, anti-inflammatory flavoprotein found to be critical in other tissues. We examined the potential role of renalase in placental development. PCR, bulk RNA sequencing, immunohistochemistry, and immunofluorescence for renalase and its binding partners, PMCA4b and PZP, were performed on human placental tissue from second-trimester and full-term placentas separated into decidua, placental villi and chorionic plates. Quantification of immunohistochemistry was used to localize renalase across time course from 17 weeks to term. Endogenous production of renalase was examined in placental tissue and organoids. Renalase and its receptor PMCA4b transcripts and proteins were present in all layers of the placenta. Estimated RNLS protein levels did not change with gestation in the decidual samples. However, placental villi contained more renalase immunoreactive cells in fetal than full-term placental samples. RNLS co-labeled with markers for Hofbauer cells and trophoblasts within the placental villi. Endogenous production of RNLS, PMCA4b, and PZP by trophoblasts was validated in placental organoids. Renalase is endogenously expressed throughout placental tissue and specifically within Hofbauer cells and trophoblasts, suggesting a potential role for renalase in placental development and function. Future studies should assess renalase's role in normal and diseased human placenta.
Topics: Chorionic Villi; Decidua; Female; Humans; Monoamine Oxidase; Placenta; Placentation; Plasma Membrane Calcium-Transporting ATPases; Pregnancy; Trophoblasts
PubMed: 35322081
DOI: 10.1038/s41598-022-08817-6 -
Open Biology Jun 2018The development of metastatic cancer is a multistage process, which often requires decades to complete. Impairments in DNA damage control and DNA repair in cancer cell... (Review)
Review
The development of metastatic cancer is a multistage process, which often requires decades to complete. Impairments in DNA damage control and DNA repair in cancer cell precursors generate genetically heterogeneous cell populations. However, despite heterogeneity most solid cancers have stereotypical behaviours, including invasiveness and suppression of immune responses that can be unleashed with immunotherapy targeting lymphocyte checkpoints. The mechanisms leading to the acquisition of stereotypical properties remain poorly understood. Reactivation of embryonic development processes in cells with unstable genomes might contribute to tumour expansion and metastasis formation. However, it is unclear whether these events are linked to immune response modulation. Tumours and embryos have non-self-components and need to avoid immune responses in their microenvironment. In mammalian embryos, neo-antigens are of paternal origin, while in tumour cells DNA mismatch repair and replication defects generate them. Inactivation of the maternal immune response towards the embryo, which occurs at the placental-maternal interface, is key to ensuring embryonic development. This regulation is accomplished by the trophoblast, which mimics several malignant cell features, including the ability to invade normal tissues and to avoid host immune responses, often adopting the same cancer immunoediting strategies. A better understanding as to whether and how genotoxic stress promotes cancer development through reactivation of programmes occurring during early stages of mammalian placentation could help to clarify resistance to drugs targeting immune checkpoint and DNA damage responses and to develop new therapeutic strategies to eradicate cancer.
Topics: Animals; Cellular Microenvironment; Cellular Reprogramming; Female; Humans; Neoplasms; Placenta; Placentation; Pregnancy; Trophoblasts
PubMed: 29950452
DOI: 10.1098/rsob.180081 -
Placenta Dec 2017In normal human placentation, uterine invasion by trophoblast cells and subsequent spiral artery remodeling depend on cooperation among fetal trophoblasts and maternal... (Review)
Review
In normal human placentation, uterine invasion by trophoblast cells and subsequent spiral artery remodeling depend on cooperation among fetal trophoblasts and maternal decidual, myometrial, immune and vascular cells in the uterine wall. Therefore, aberrant function of anyone or several of these cell-types could theoretically impair placentation leading to the development of preeclampsia. Because trophoblast invasion and spiral artery remodeling occur during the first half of pregnancy, the molecular pathology of fetal placental and maternal decidual tissues following delivery may not be informative about the genesis of impaired placentation, which transpired months earlier. Therefore, in this review, we focus on the emerging prospective evidence supporting the concept that deficient or defective endometrial maturation in the late secretory phase and during early pregnancy, i.e., pre-decidualization and decidualization, respectively, may contribute to the genesis of preeclampsia. The first prospectively-acquired data directly supporting this concept were unexpectedly revealed in transcriptomic analyses of chorionic villous samples (CVS) obtained during the first trimester of women who developed preeclampsia 5 months later. Additional supportive evidence arose from investigations of Natural Killer cells in first trimester decidua from elective terminations of women with high resistance uterine artery indices, a surrogate for deficient trophoblast invasion. Last, circulating insulin growth factor binding protein-1, which is secreted by decidual stromal cells was decreased during early pregnancy in women who developed preeclampsia. We conclude this review by making recommendations for further prospectively-designed studies to corroborate the concept of endometrial antecedents of preeclampsia. These studies could also enable identification of women at increased risk for developing preeclampsia, unveil the molecular mechanisms of deficient or defective (pre)decidualization, and lead to preventative strategies designed to improve (pre)decidualization, thereby reducing risk for preeclampsia development.
Topics: Decidua; Female; Gene Expression; Humans; Placenta; Placentation; Pre-Eclampsia; Pregnancy
PubMed: 28693893
DOI: 10.1016/j.placenta.2017.06.005 -
Biology of Reproduction May 2013MicroRNAs are a class of noncoding small RNAs that regulate the expression of nearly 30% of all the human genes and participate in all fundamental cell processes.... (Review)
Review
MicroRNAs are a class of noncoding small RNAs that regulate the expression of nearly 30% of all the human genes and participate in all fundamental cell processes. Genome-wide analysis has revealed that human placenta expresses more than 600 miRNA species, including placenta-specific ones with high levels of expression. Comparative analysis also has revealed many differentially expressed miRNAs with either high or low levels of expression in human placentas from normal versus preeclamptic pregnancies, indicating an important role of miRNAs in normal and pathological placental physiology. Although limited information is currently available as to how miRNA regulates human placental development and function, there are studies suggesting that preeclampsia-associated differentially expressed miRNAs possess critical roles in regulating placental development and function via targeting specific genes with diverse known functions. Herein we summarize the current findings regarding the expression of placental miRNAs and their function, especially in the trophoblast cells. We have recently found that the angiogenesis-associated miR-17-family miRNAs are upregulated in preeclamptic compared with normotensive placentas and they target the ephrin-B2/Eph receptor B4 (EPHB4) system. Because ephrin-B2 and EPHB4 has been previously shown to play a crucial role in trophoblast invasion into maternal spiral artery and vascular patterning during early human placental development, the miR-17-ephrin-B2/EPHB4 pathway seems to be a novel miRNA pathway for regulating normal and aberrant placental development during preeclampsia.
Topics: Female; Humans; MicroRNAs; Placenta; Placentation; Pre-Eclampsia; Pregnancy
PubMed: 23575145
DOI: 10.1095/biolreprod.113.107805 -
The Journal of Reproduction and... Feb 2007In cattle, the mechanisms underlying implantation and placental development are still unclear. Synepitheliochorial placentation in cattle is noninvasive, and thus... (Review)
Review
In cattle, the mechanisms underlying implantation and placental development are still unclear. Synepitheliochorial placentation in cattle is noninvasive, and thus generates limited interest in terms of degradation and remodeling of endometrial tissues. The overall purpose of this study was three-fold: (1) to examine the gene circuitry around the implantation window, (2) to understand development of the placenta during the peri-implantation period by using a uteroplacental cDNA microarray, and (3) to study the roles of molecules involved in endometrial remodeling. Bovine trophoblastic binucleate cell-specific molecules, such as pregnancy-associated glycoproteins (PAGs), placental lactogen (PL), and prolactin-related proteins (PRPs), were markedly expressed in binucleate cells (BNCs) around implantation. The expression of PRP-1 was specific to the caruncular (CAR) area of the gravid uterine horn. Gelatinases (MMP-2 and -9) in association with heparanase may be central to endometrial remodeling. In situ hybridization analyses of PAGs, PRPs, PL, and heparanase suggested that BNCs expressed these molecules simultaneously. Future studies will further investigate the specific roles of these molecules in placentogenesis. The uteroplacental cDNA microarray presented cascades of molecular signatures not only for the endometrium but also for the intricate dialogue at the level of the feto-maternal interface in cattle. Placentome morphogenesis potentially parallels the dynamic multigenic circuitry and regulates the cell cycle in the endometrium. The roles of BNCs and their secreted molecules remain an enigma, particularly with regard to the adhesion process and endometrial remodeling, which is the focus of this study.
Topics: Animals; Cattle; Embryo Implantation; Female; Gelatinases; Gene Expression Profiling; Hormones; Placenta; Placentation; Pregnancy; Uterus
PubMed: 17332695
DOI: 10.1262/jrd.18123 -
Romanian Journal of Morphology and... 2009Placental morphology and vascularization are important stages in the evolution of pregnancies. Placental morphogenesis and angiogenesis processes are studied by... (Review)
Review
Placental morphology and vascularization are important stages in the evolution of pregnancies. Placental morphogenesis and angiogenesis processes are studied by two-dimensional, three-dimensional and Doppler ultrasound. Ultrasound methods provide important data on the physiology and pathophysiology of fetal-placental exchange. The macroscopic and microscopic study of the placenta brings valuable information on the possible structural changes and implicitly allows assessing fetal-placental circulation. The ultrasound and microscopic evaluation of the placenta are complementary means of examination for the assessment of fetal-maternal exchange. These methods of investigation can be applied in the context of a strict knowledge of placental morphogenesis and angiogenesis.
Topics: Chorionic Villi; Female; Humans; Maternal-Fetal Exchange; Morphogenesis; Neovascularization, Physiologic; Placenta; Placental Circulation; Placentation; Pregnancy; Ultrasonography, Doppler
PubMed: 19942949
DOI: No ID Found -
Reproduction (Cambridge, England) Jul 2023Healthy development of the placenta is dependent on trophoblast cell migration and reduced oxidative stress presence. This article describes how a phytoestrogen found in...
IN BRIEF
Healthy development of the placenta is dependent on trophoblast cell migration and reduced oxidative stress presence. This article describes how a phytoestrogen found in spinach and soy causes impaired placental development during pregnancy.
ABSTRACT
Although vegetarianism has grown in popularity, especially among pregnant women, the effects of phytoestrogens in placentation lack understanding. Factors such as cellular oxidative stress and hypoxia and external factors including cigarette smoke, phytoestrogens, and dietary supplements can regulate placental development. The isoflavone phytoestrogen coumestrol was identified in spinach and soy and was found to not cross the fetal-placental barrier. Since coumestrol could be a valuable supplement or potent toxin during pregnancy, we sought to examine its role in trophoblast cell function and placentation in murine pregnancy. After treating trophoblast cells (HTR8/SVneo) with coumestrol and performing an RNA microarray, we determined 3079 genes were significantly changed with the top differentially changed pathways related to the oxidative stress response, cell cycle regulation, cell migration, and angiogenesis. Upon treatment with coumestrol, trophoblast cells exhibited reduced migration and proliferation. Additionally, we observed increased reactive oxygen species accumulation with coumestrol administration. We then examined the role of coumestrol within an in vivo pregnancy by treating wildtype pregnant mice with coumestrol or vehicle from day 0 to 12.5 of gestation. Upon euthanasia, fetal and placental weights were significantly decreased in coumestrol-treated animals with the placenta exhibiting a proportional decrease with no obvious changes in morphology. Therefore, we conclude that coumestrol impairs trophoblast cell migration and proliferation, causes accumulation of reactive oxygen species, and reduces fetal and placental weights in murine pregnancy.
Topics: Pregnancy; Female; Mice; Humans; Animals; Placenta; Coumestrol; Phytoestrogens; Reactive Oxygen Species; Cell Line; Placentation; Trophoblasts; Oxidative Stress
PubMed: 37078791
DOI: 10.1530/REP-23-0017 -
Scientific Reports Jul 2023Trophectoderm cells of the blastocyst are the precursor of the placenta that is comprised of trophoblast, endothelial and smooth muscle cells. Since trophoectoderm cells...
Trophectoderm cells of the blastocyst are the precursor of the placenta that is comprised of trophoblast, endothelial and smooth muscle cells. Since trophoectoderm cells are epithelial in nature, epithelial mesenchymal transition (EMT) of trophoblast stem (TS) cells might play pivotal role in placental morphogenesis. However, the molecular regulation of EMT during placental development and trophoblast differentiation still remained elusive. In this report, we sought to identify the molecular signature that regulates EMT during placental development and TS cell differentiation in mice. On E7.5 onwards the TS cells, located in the ectoplacental cone (EPC), rapidly divide and differentiate leading to formation of placenta proper. Using a real time PCR based array of functional EMT transcriptome with RNA from mouse implantation sites (IS) on E7.5 and E9.5, it was observed that there was an overall reduction of EMT gene expression in the IS as gestation progressed from E7.5 to E9.5 albeit the levels of EMT gene expression were substantial on both days. Further validation of array results using real time PCR and western blot analysis showed significant decrease in EMT-associated genes that included (a) transcription factors (Snai2, Zeb1, Stat3 and Foxc2), (b) extracellular matrix and cell adhesion related genes (Bmp1, Itga5, Vcan and Col3A1), (c) migration and motility- associated genes (Vim, Msn and FN1) and (d) differentiation and development related genes (Wnt5b, Jag1 and Cleaved Notch-1) on E9.5. To understand whether EMT is an ongoing process during placentation, the EMT-associated signatures genes, prevalent on E 7.5 and 9.5, were analysed on E12.5, E14.5 and E17.5 of mouse placenta. Interestingly, expression of these EMT-signature proteins were significantly higher at E12.5 though substantial expressions was observed in placenta with progression of gestation from mid- to late. To evaluate whether TS cells have the potential to undergo EMT ex vivo, TS cells were subjected to EMT induction, which was confirmed using morphological analysis and marker gene expression. Induction of EMT in TS cells showed similar gene expression profile of placental EMT. These results have broad biological implications, as inadequate mesenchymal transition leading to improper trophoblast-vasculogenic mimicry leads to placental pathophysiology and pregnancy failure.
Topics: Pregnancy; Female; Animals; Mice; Trophoblasts; Placenta; Epithelial-Mesenchymal Transition; Placentation; Cell Differentiation; Stem Cells
PubMed: 37414855
DOI: 10.1038/s41598-023-37977-2