Oxygen governs Galβ1–3GalNAc epitope in human placenta

2013 ◽  
Vol 305 (9) ◽  
pp. C931-C940 ◽  
Author(s):  
Leonardo Ermini ◽  
Jayonta Bhattacharjee ◽  
Antonella Spagnoletti ◽  
Nicoletta Bechi ◽  
Silvia Aldi ◽  
...  
Keyword(s):  
Oxygen Tension ◽  
Human Placenta ◽  
Physiological State ◽  
First Trimester ◽  
Signal Molecules ◽  
Control Mechanisms ◽  
Low Oxygen ◽  
Placental Development ◽  
Human Trophoblast ◽  
Cell Functions

It is becoming increasingly apparent that the dynamics of glycans reflect the physiological state of cells involved in several cell functions including growth, response to signal molecules, migration, as well as adhesion to, interaction with, and recognition of other cells. The presence of glycoconjugates in human placenta suggests their major role in maternal-fetal exchanges, intercellular adhesion, cellular metabolism, and villous vessel branching. Although several studies have described glycoconjugate distribution in the human placenta descriptions of their physiological function and control mechanisms during placental development are lacking. In this study we investigated the developmental distribution and regulation of placental core 1 O- and N-glycans focusing on early and late first trimester human pregnancy. To define the control mechanisms of the oligosaccharide chains during early placentation process, chorionic villous explants and human trophoblast cell lines were exposed to various oxygen levels. We found that oxygen tension regulates changes in core-1 O-glycan (the disaccharide Galβ1–3GalNAc) epitope expression levels. Moreover, by double affinity chromatography and subsequent analysis with mass spectrometry, we identified in the heat shock protein 90-α (HSP90α) a good candidate as carrier of the Galβ1–3GalNAc epitope at low oxygen tension. Our results support a fundamental role of oxygen tension in modulating glycosylation of proteins during placental development.

scholarly journals Trophoblast lineage specification, differentiation and their regulation by oxygen tension

2018 ◽  
Vol 236 (1) ◽  
pp. R43-R56 ◽  
Author(s):  
Ching-Wen Chang ◽  
Anna K Wakeland ◽  
Mana M Parast
Keyword(s):  
Oxygen Tension ◽  
First Trimester ◽  
Arterial Blood Flow ◽  
Extravillous Trophoblast ◽  
Low Oxygen ◽  
Epithelial Stem Cells ◽  
Placental Development ◽  
Trophoblast Differentiation ◽  
Arterial Blood ◽  
Low Oxygen Tension

Development of the early embryo takes place under low oxygen tension. Under such conditions, the embryo implants and the trophectoderm, the outer layer of blastocyst, proliferate, forming the cytotrophoblastic shell, the early placenta. The cytotrophoblasts (CTBs) are the so-called epithelial ‘stem cells’ of the placenta, which, depending on the signals they receive, can differentiate into either extravillous trophoblast (EVT) or syncytiotrophoblast (STB). EVTs anchor the placenta to the uterine wall and remodel maternal spiral arterioles in order to provide ample blood supply to the growing fetus. STBs arise through CTB fusion, secrete hormones necessary for pregnancy maintenance and form a barrier across which nutrient and gas exchange can take place. The bulk of EVT differentiation occurs during the first trimester, before the onset of maternal arterial blood flow into the intervillous space of the placenta, and thus under low oxygen tension. These conditions affect numerous signaling pathways, including those acting through hypoxia-inducible factor, the nutrient sensor mTOR and the endoplasmic reticulum stress-induced unfolded protein response pathway. These pathways are known to be involved in placental development and disease, and specific components have even been identified as directly involved in lineage-specific trophoblast differentiation. Nevertheless, much controversy surrounds the role of hypoxia in trophoblast differentiation, particularly with EVT. This review summarizes previous studies on this topic, with the intent of integrating these results and synthesizing conclusions that resolve some of the controversy, but then also pointing to remaining areas, which require further investigation.

scholarly journals Proteome Profiling of Human Placenta Reveals Developmental Stage-Dependent Alterations in Protein Signature

2021 ◽  
Author(s):  
Sara Khorami Sarvestani ◽  
Sorour Shojaeian ◽  
Negar Vanaki ◽  
Behrouz Gharesi-Fard ◽  
Mehdi Amini ◽  
...  
Keyword(s):  
Human Placenta ◽  
First Trimester ◽  
Full Term ◽  
Chemical Stimulus ◽  
Health It ◽  
Low Oxygen ◽  
Placental Development ◽  
Liquid Chromatography Tandem Mass ◽  
Complex Organ ◽  
Protein Signature

Abstract Introduction Placenta is a complex organ that plays a significant role in the maintenance of pregnancy health. It is a dynamic organ that undergoes dramatic changes in growth and development at different stages of gestation. In the first-trimester, the conceptus develops in a low oxygen environment that favors organogenesis in the embryo and cell proliferation and angiogenesis in the placenta; later in pregnancy, higher oxygen concentration is required to support the rapid growth of the fetus. This transition, which appears unique to the human placenta, must be finely tuned through successive rounds of protein signature alterations. This study compares placental proteome in normal first-trimester (FT) and term human placentas (TP). MethodsNormal human first-trimester and term placental samples were collected and differentially expressed proteins were identified using two-dimensional liquid chromatography-tandem mass spectrometry.ResultsDespite the overall similarities, 120 proteins were differently expressed in first and term placentas. Out of these, 120 proteins, expression of 72 was up-regulated and that of 48 was down-regulated in the first when compared with the full term placentas. Twenty out of 120 differently expressed proteins were sequenced, among them seven showed increased (GRP78, PDIA3, ENOA, ECH1, PRDX4, ERP29, ECHM), eleven decreased (TRFE, ALBU, K2C1, ACTG, CSH2, PRDX2, FABP5, HBG1, FABP4, K2C8, K1C9) expression in first-trimester compared to the full-term placentas and two proteins exclusively expressed in first-trimester placentas (MESD, MYDGF). DiscussionAccording to Reactome and PANTHER softwares, these proteins were mostly involved in response to chemical stimulus and stress, regulation of biological quality, programmed cell death, hemostatic and catabolic processes, protein folding, cellular oxidant detoxification, coagulation and retina homeostasis. Elucidation of alteration in protein signature during placental development would provide researchers with a better understanding of the critical biological processes of placentogenesis and delineate proteins involved in regulation of placental function during development.

scholarly journals Proteome profiling of human placenta reveals developmental stage-dependent alterations in protein signature

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Sara Khorami Sarvestani ◽  
Sorour Shojaeian ◽  
Negar Vanaki ◽  
Behrouz Ghresi-Fard ◽  
Mehdi Amini ◽  
...  
Keyword(s):  
Human Placenta ◽  
First Trimester ◽  
Full Term ◽  
Chemical Stimulus ◽  
Health It ◽  
Low Oxygen ◽  
Placental Development ◽  
Liquid Chromatography Tandem Mass ◽  
Normal Human ◽  
Protein Signature

Abstract Introduction Placenta is a complex organ that plays a significant role in the maintenance of pregnancy health. It is a dynamic organ that undergoes dramatic changes in growth and development at different stages of gestation. In the first-trimester, the conceptus develops in a low oxygen environment that favors organogenesis in the embryo and cell proliferation and angiogenesis in the placenta; later in pregnancy, higher oxygen concentration is required to support the rapid growth of the fetus. This oxygen transition, which appears unique to the human placenta, must be finely tuned through successive rounds of protein signature alterations. This study compares placental proteome in normal first-trimester (FT) and term human placentas (TP). Methods Normal human first-trimester and term placental samples were collected and differentially expressed proteins were identified using two-dimensional liquid chromatography-tandem mass spectrometry. Results Despite the overall similarities, 120 proteins were differently expressed in first and term placentas. Out of these, 72 were up-regulated and 48 were down-regulated in the first when compared with the full term placentas. Twenty out of 120 differently expressed proteins were sequenced, among them seven showed increased (GRP78, PDIA3, ENOA, ECH1, PRDX4, ERP29, ECHM), eleven decreased (TRFE, ALBU, K2C1, ACTG, CSH2, PRDX2, FABP5, HBG1, FABP4, K2C8, K1C9) expression in first-trimester compared to the full-term placentas and two proteins exclusively expressed in first-trimester placentas (MESD, MYDGF). Conclusion According to Reactome and PANTHER softwares, these proteins were mostly involved in response to chemical stimulus and stress, regulation of biological quality, programmed cell death, hemostatic and catabolic processes, protein folding, cellular oxidant detoxification, coagulation and retina homeostasis. Elucidation of alteration in protein signature during placental development would provide researchers with a better understanding of the critical biological processes of placentogenesis and delineate proteins involved in regulation of placental function during development.

scholarly journals HYPOXIA AND REPRODUCTIVE HEALTH: Oxygen and development of the human placenta

Reproduction ◽  
2021 ◽  
Vol 161 (1) ◽  
pp. F53-F65 ◽  
Author(s):  
Graham J Burton ◽  
Tereza Cindrova-Davies ◽  
Hong wa Yung ◽  
Eric Jauniaux
Keyword(s):  
Oxidative Stress ◽  
Human Placenta ◽  
Epithelial Mesenchymal Transition ◽  
First Trimester ◽  
Extravillous Trophoblast ◽  
Low Oxygen ◽  
Placental Development ◽  
Mesenchymal Transition ◽  
Oxygen Concentrations

Development of the human placenta takes place in contrasting oxygen concentrations at different stages of gestation, from ~20 mmHg during the first trimester rising to ~60 mmHg at the start of the second trimester before gradually declining to ~40 mmHg at term. In view of these changes, the early placenta has been described as ‘hypoxic’. However, placental metabolism is heavily glycolytic, supported by the rich supply of glucose from the endometrial glands, and there is no evidence of energy compromise. On the contrary, the trophoblast is highly proliferative, with the physiological low-oxygen environment promoting maintenance of stemness in progenitor populations. These conditions favour the formation of the cytotrophoblastic shell that encapsulates the conceptus and interfaces with the endometrium. Extravillous trophoblast cells on the outer surface of the shell undergo an epithelial-mesenchymal transition and acquire invasive potential. Experimental evidence suggests that these changes may be mediated by the higher oxygen concentration present within the placental bed. Interpreting in vitro data is often difficult, however, due to the use of non-physiological oxygen concentrations and trophoblast-like cell lines or explant models. Trophoblast is more vulnerable to hyperoxia or fluctuating levels of oxygen than to hypoxia, and some degree of placental oxidative stress likely occurs in all pregnancies towards term. In complications of pregnancy, such as early-onset pre-eclampsia, malperfusion generates high levels of oxidative stress, causing release of factors that precipitate the maternal syndrome. Further experiments are required using genuine trophoblast progenitor cells and physiological concentrations to fully elucidate the pathways by which oxygen regulates placental development.

scholarly journals Effects of adiponectin on human trophoblast invasion

2010 ◽  
Vol 207 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Delphine Benaitreau ◽  
Esther Dos Santos ◽  
Marie-Christine Leneveu ◽  
Nadia Alfaidy ◽  
Jean-Jacques Feige ◽  
...  
Keyword(s):  
First Trimester ◽  
Extravillous Trophoblast ◽  
Trophoblast Invasion ◽  
Placental Development ◽  
Independent Manner ◽  
Human Trophoblast ◽  
Pathological Conditions ◽  
First Trimester Of Pregnancy ◽  
Insight Into

Adiponectin is an adipokine with insulin-sensitizing, anti-inflammatory, anti-atherogenic, and anti-proliferative effects. The expression of specific adiponectin receptors in the placenta and in the endometrium suggests a role for this cytokine in placental development, but this role has not yet been elucidated. The invasion of trophoblast cells during the first trimester of pregnancy being crucial to placentation process, we have studied adiponectin effects on human trophoblast invasive capacities. We found that adiponectin stimulated human trophoblast cell migration in HTR-8/SVneo cells in a dose-independent manner. In addition, adiponectin also significantly enhanced invasion of HTR-8/SVneo cells and of human extravillous trophoblast from first trimester placenta. These pro-invasive effects of adiponectin in human trophoblasts seem to be mediated in part via increased matrix metalloproteinases (MMP2 and MMP9) activities and via repression of TIMP2 mRNA expression. Our results suggest that adiponectin could be a positive regulator of the early invasion process by modulating the MMP/TIMP balance. Moreover, these results provide an insight into the role of adiponectin in pathological conditions characterized by insufficient or excessive trophoblast invasion.

Different regulation of IRE1α and eIF2α pathways by oxygen and insulin in ACH-3P trophoblast model

Reproduction ◽  
2021 ◽  
Author(s):  
Veronika Tandl ◽  
Denise Hoch ◽  
Julia Bandres-Meriz ◽  
Sanela Nikodijevic ◽  
Gernot Desoye ◽  
...  
Keyword(s):  
Er Stress ◽  
Early Pregnancy ◽  
Physiological Role ◽  
Brefeldin A ◽  
First Trimester ◽  
Fold Change ◽  
Low Oxygen ◽  
Placental Development ◽  
Eif2α Phosphorylation ◽  
The Unfolded Protein Response

Endoplasmic reticulum (ER)-stress activates the unfolded protein response (UPR), which plays a (patho)physiological role in the placenta. Oxygen and hyperinsulinemia are major regulators of placental development. Thus, we hypothesized that oxygen, insulin and their interplay modulate ER-stress in early pregnancy. Using the human first trimester trophoblast cell line ACH-3P, we quantified mRNA and protein of several members of UPR by RT-qPCR and Western blotting, respectively. ER-stress induction using tunicamycin and brefeldin A resulted in increased CHOP (4.6-fold change; P ≤ 0.001), XBP1 expression (1.7- and 1.3-fold change, respectively; P ≤ 0.001 and P < 0.05) and XBP1 splicing (7.9- and 12.8-fold change, respectively; P ≤ 0.001). We subsequently analyzed the effect of oxygen (6.5%, 2.5%), insulin (0.1-10 nM) and their interaction using ANCOVA adjusted for cell passage as co-variate. Although GRP78 protein remained unaffected, low oxygen (2.5% O2) increased IRE1α phosphorylation (+52%; P < 0.05) and XBP1 splicing (1.8-fold change; P ≤ 0.001) after 24h, while eIF2α protein and CHOP expression were downregulated (–28%; P < 0.05 and –24%; P ≤ 0.001; respectively). eIF2α phosphorylation was also reduced after 48h by low oxygen (–61%; P < 0.05), but increased in the presence of insulin (+46%; P ≤ 0.01). These changes were not PERK-mediated, since PERK phosphorylation and total protein were not altered. Overall, our results suggest that IRE1α and eIF2α UPR-pathways are differentially regulated by oxygen and insulin in early pregnancy.

Microvillous membrane potential (E m) in villi from first trimester human placenta: comparison toE m at term

1997 ◽  
Vol 273 (4) ◽  
pp. R1519-R1528 ◽  
Author(s):  
T. J. Birdsey ◽  
R. D. H. Boyd ◽  
C. P. Sibley ◽  
S. L. Greenwood
Keyword(s):  
Membrane Potential ◽  
Human Placenta ◽  
First Trimester ◽  
Major Contributor ◽  
Placental Development ◽  
Ion Conductance ◽  
Placental Villi

The microvillous membrane (MVM) potential ( E m) of first trimester human placental villi was measured and compared with that in villi from term human placentas. The median E m in first trimester villi (−28 mV) was significantly more negative than that at term (−21 mV; P < 0.001). The median E m measured in villi from early ( weeks 6–11) first trimester (−32 mV) was significantly more negative than that in late ( weeks 12 and 13) first trimester villi (−24 mV; P < 0.001). Elevating extracellular KCl concentration induced a significant depolarization of E m in both first trimester and term villi ( P < 0.05 and P < 0.001, respectively). The magnitude of this depolarization was greater in first trimester than at term, indicating that the ion conductance of the MVM changes with gestation. Exposure to ouabain induced a significant depolarization of E m (3 mV: P < 0.05) in first trimester villi but had little effect at term. These results suggest that microvillous membrane electrophysiology changes with placental development. An alteration in the relative K+:Cl−conductance of the MVM is likely to be a major contributor to the change in the magnitude of E m.

scholarly journals Tubulin detyrosination promotes human trophoblast syncytium formation

2019 ◽  
Vol 11 (11) ◽  
pp. 967-978 ◽  
Author(s):  
Rui Wang ◽  
Ruoxuan Yu ◽  
Cheng Zhu ◽  
Hai-Yan Lin ◽  
Xiaoyin Lu ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Syncytium Formation ◽  
First Trimester ◽  
Trophoblast Cells ◽  
Placental Development ◽  
Human Trophoblast ◽  
Junction Protein ◽  
Elevated Expression ◽  
Surface Localization ◽  
Cytotrophoblast Cells

Abstract Human trophoblast syncytialization is one of the most important yet least understood events during placental development. In this study, we found that detyrosinated α-tubulin (detyr-α-tub), which is negatively regulated by tubulin tyrosine ligase (TTL), was elevated during human placental cytotrophoblast fusion. Correspondingly, relatively high expression of TTL protein was observed in first-trimester human placental cytotrophoblast cells, but fusing trophoblast cells exhibited much lower levels of TTL. Notably, fusion of preeclamptic cytotrophoblast cells was compromised but could be partially rescued by knockdown of TTL levels. Mechanistically, chronic downregulation of TTL in trophoblast cells resulted in significantly elevated expression of detyr-α-tub. Restoration of detyr-α-tub thus contributed to the cell surface localization of the fusogenic protein Syncytin-2 and the gap junction protein Connexin 43 (Cx43), which in turn promoted successful fusion between trophoblast cells. Taken together, the results suggest that tubulin detyrosination plays an essential role in human trophoblast fusogenic protein aggregation and syncytialization. Insufficient tubulin detyrosination leads to defects in syncytialization and potentially to the onset of preeclampsia.

scholarly journals Cytological localization of chorionic gonadotropin alpha and placental lactogen mRNAs during development of the human placenta.

1982 ◽  
Vol 93 (1) ◽  
pp. 190-198 ◽  
Author(s):  
M Hoshina ◽  
M Boothby ◽  
I Boime
Keyword(s):  
Chorionic Gonadotropin ◽  
Human Placenta ◽  
First Trimester ◽  
Placental Lactogen ◽  
Mrna Synthesis ◽  
Placental Development ◽  
Trophoblast Differentiation ◽  
Constant Rate ◽  
Alpha Gene ◽  
Cytological Localization

Probes derived from clones bearing cDNAs corresponding to the alpha subunit of human chorionic gonadotropin (hCG) and human placental lactogen (hPL) were used to localize their respective mRNAs cytologically in sections of first trimester and term human placenta. hPL mRNA was exclusively localized to the syncytial layer, hCG alpha mRNA was found in the syncytial layer and also in some differentiating cytotrophoblasts. Hybridization was specific because no signal was observed when labeled pBR322 was hybridized to placental sections or when the placental probes were hybridized to sections of human tonsils. In addition, RNA in placental interstitial cells did not hybridize with hCG alpha and hPL probes. Hybridization with the hCG alpha probe was much greater in first trimester than in term sections, whereas hPL signals were comparable in both first trimester and term placentae. Syncytial formation proceeds through cellular intermediates of cytotrophoblastic origin, and the data suggest that transcription of the hCG alpha gene is initiated before the completion of syncytial formation. In contrast, hPL mRNA synthesis starts later in trophoblast differentiation, likely after the stage of syncytial formation. The data also suggested that hCG alpha mRNA synthesis becomes attenuated but that hPL is transcribed at a rather constant rate during placental development.

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