Effects of anti β2-GPI antibody on the expression and function of TLR in choriocarcinoma cell and first trimester trophoblast

2012 ◽  
Vol 94 (1) ◽  
pp. 104
Author(s):  
A. Nakamura ◽  
T. Yamamoto ◽  
H. Azuma ◽  
E. Kato ◽  
G. Ichikawa ◽  
...  
Keyword(s):  
Placenta ◽  
2011 ◽  
Vol 32 ◽  
pp. S333-S334
Author(s):  
L. Ermini ◽  
A. Spagnoletti ◽  
N. Bechi ◽  
S. Aldi ◽  
J. Bhattacharjee ◽  
...  

2007 ◽  
Vol 57 (1) ◽  
pp. 67-80 ◽  
Author(s):  
Melissa J. Costello ◽  
Shawna K. Joyce ◽  
Vikki M. Abrahams

2016 ◽  
Vol 64 (12) ◽  
pp. 769-784 ◽  
Author(s):  
Tina Storm ◽  
Erik I. Christensen ◽  
Julie Nelly Christensen ◽  
Tine Kjaergaard ◽  
Niels Uldbjerg ◽  
...  

The membrane receptor megalin is crucial for normal fetal development. Besides its expression in the developing fetus, megalin is also expressed in the human placenta. Similar to its established function in the kidney proximal tubules, placental megalin has been proposed to mediate uptake of vital nutrients. However, details of megalin expression, subcellular localization, and function in the human placenta remain to be established. By immunohistochemical analyses of first trimester and term human placenta, we showed that megalin is predominantly expressed in cytotrophoblasts, the highly proliferative cells in placenta. Only limited amounts of megalin could be detected in syncytiotrophoblasts and least in term placenta syncytiotrophoblasts. Immunocytochemical analyses furthermore showed that placental megalin associates with structures of the endolysosomal apparatus. Combined, our results clearly place placental megalin in the context of endocytosis and trafficking of ligands. However, due to the limited expression of megalin in syncytiotrophoblasts, especially in term placenta, it appears that the main role for placental megalin is not to mediate uptake of nutrients from the maternal bloodstream, as previously proposed. In contrast, our results point toward novel and complex functions for megalin in the cytotrophoblasts. Thus, we propose that the perception of placental megalin localization and function should be revised.


1998 ◽  
pp. 536-542 ◽  
Author(s):  
A Berghout ◽  
W Wiersinga

An analysis of all available studies of thyroid size and function in pregnancy reveals that thyroid size, estimated by inspection and palpation or measured more accurately by ultrasonography, increases in pregnancy in areas of iodine deficiency but not in those with sufficient iodine. The increase in average thyroid size is within the normal range, and can partly be prevented by treatment with extra iodine or thyroxine. There is a slight transient increase in free thyroxine in the first trimester, probably as a result of physiological stimulation of thyroid function by human choriogonadotrophin. These levels then decrease by about 30% to low normal values in the second and third trimesters of pregnancy in both iodine-depleted and -replete areas. These changes resemble those of non-thyroidal illness and may well play a role in reducing energy expenditure during pregnancy. The increase in thyroid size in iodine-deficient areas is probably due to autoregulatory mechanisms of iodine on thyroid growth. The hypothesis is supported by the fact that, during pregnancy, thyroid volume and thyroid function adapt in a physiological way to meet the increased demands for iodine and energy.


2021 ◽  
Author(s):  
Matthew Shannon ◽  
Jennet Baltayeva ◽  
Barbara Castellana ◽  
Jasmin Wachter ◽  
Samantha Yoon ◽  
...  

The establishment and function of the human placenta is dependent on specialized cells called trophoblasts. Progenitor cytotrophoblasts (CTBs) differentiate along one of two cellular trajectories: the villous or extravillous pathways. CTBs committed to the villous pathway fuse with neighboring CTBs forming the outer multinucleated syncytiotrophoblast layer (SCT), while CTBs committed to the extravillous pathway develop into multi-layered cell columns that anchor the placenta to uterine tissue. At distal column sites, column CTBs differentiate into invasive extravillous trophoblasts (EVT) that facilitate uterine remodeling of spiral arteries and modulate the maternal immune response to fetal antigen. Unfortunately, little is known about the cellular and molecular processes controlling human trophoblast stem cell maintenance and differentiation into these critical trophoblast sub-lineages. To address this, our laboratory established a single cell RNA sequencing (scRNA-seq) dataset from first trimester placentas to identify molecular programs and cell states important in trophoblast progenitor establishment, renewal, and differentiation. Using this dataset, eight distinct trophoblast states were identified, representing progenitor cytotrophoblasts, intermediate column CTBs, syncytiotrophoblast progenitors, and terminally differentiated EVT. Lineage trajectory analysis identified a CTB origin that was reproduced in human trophoblast stem cell organoids. Heightened expression of basal cell adhesion molecule (BCAM) defined this primitive state, where CTBs selected for high levels of surface BCAM expression generated larger clonally-derived organoids than did CTB counterparts expressing lower levels of BCAM. Together, this work resolves complex gene networks within human trophoblast progenitor cells, and identifies BCAM as marker that defines an up-stream progenitor origin.


2011 ◽  
Vol 85 (Suppl_1) ◽  
pp. 281-281
Author(s):  
Francesca Mossa ◽  
Siobhan W. Walsh ◽  
Thomas B. Hildebrandt ◽  
David A. Kenny ◽  
Pat Lonergan ◽  
...  

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1723-1731 ◽  
Author(s):  
Karen Forbes ◽  
Benoit Souquet ◽  
Rebecca Garside ◽  
John D. Aplin ◽  
Melissa Westwood

Maternal IGFs regulate cytotrophoblast proliferation and, thereby, placental growth and function. IGF bioavailability is controlled by IGF-binding proteins (IGFBPs); in placenta, IGFBP-3 is particularly abundant. In other systems, IGFBP-3 can regulate cellular events independently of IGFs; these effects are thought to be mediated by TGFβ receptors (TβR). We have examined IGFBP-3 regulation of IGF-dependent and -independent cytotrophoblast proliferation in first-trimester placental explants and the role of TβRII in mediating these effects. In the presence of IGFBP-3 (50 nm), IGF-induced (10 nm) proliferation (monitored by immunohistochemical analysis of Ki67 expression and bromodeoxyuridine incorporation) was significantly reduced (P < 0.05). IGFBP-3 also reduced basal proliferation independently of IGF receptor signaling. Immunohistochemical analysis demonstrated that TGFβ signaling molecules [TGFβ receptor I (TβRI), TβRII, TβRV, Smad-2, and ERK] are expressed in syncytium and/or cytotrophoblast. TGFβ1 (10 ng/ml) enhanced cytotrophoblast proliferation and activated both Smad-2 and ERK-1/2, whereas IGFBP-3 activated only Smad-2. The function of both TGFβ1 and IGFBP-3 was attenuated by a TβRII function-blocking antibody and by small interfering RNA-mediated knockdown of TβRII (P < 0.05); this was accompanied by a reduction in Smad-2 activation. This study demonstrates that both TGFβ1 and IGFBP-3 signal through TβRI/II to influence human cytotrophoblast proliferation. However, downstream pathways are distinct, because IGFBP-3 acts only through Smad-2, whereas TGFβ1 also phosphorylates ERK, resulting in opposite effects on cytotrophoblast proliferation. The effects of maternal growth signals on placental growth and function therefore depend on the balance of ligands, receptors, and signaling molecules at the syncytiotrophoblast surface. Therapeutic manipulation of this balance might offer a strategy to optimize placental development and pregnancy outcome.


2019 ◽  
Vol 294 (46) ◽  
pp. 17301-17313 ◽  
Author(s):  
Jessica Milano-Foster ◽  
Soma Ray ◽  
Pratik Home ◽  
Avishek Ganguly ◽  
Bhaswati Bhattacharya ◽  
...  

A successful pregnancy is critically dependent upon proper placental development and function. During human placentation, villous cytotrophoblast (CTB) progenitors differentiate to form syncytiotrophoblasts (SynTBs), which provide the exchange surface between the mother and fetus and secrete hormones to ensure proper progression of pregnancy. However, epigenetic mechanisms that regulate SynTB differentiation from CTB progenitors are incompletely understood. Here, we show that lysine-specific demethylase 1 (LSD1; also known as KDM1A), a histone demethylase, is essential to this process. LSD1 is expressed both in CTB progenitors and differentiated SynTBs in first-trimester placental villi; accordingly, expression in SynTBs is maintained throughout gestation. Impairment of LSD1 function in trophoblast progenitors inhibits induction of endogenous retrovirally encoded genes SYNCYTIN1/endogenous retrovirus group W member 1, envelope (ERVW1) and SYNCYTIN2/endogenous retrovirus group FRD member 1, envelope (ERVFRD1), encoding fusogenic proteins critical to human trophoblast syncytialization. Loss of LSD1 also impairs induction of chorionic gonadotropin α (CGA) and chorionic gonadotropin β (CGB) genes, which encode α and β subunits of human chorionic gonadotrophin (hCG), a hormone essential to modulate maternal physiology during pregnancy. Mechanistic analyses at the endogenous ERVW1, CGA, and CGB loci revealed a regulatory axis in which LSD1 induces demethylation of repressive histone H3 lysine 9 dimethylation (H3K9Me2) and interacts with transcription factor GATA2 to promote RNA polymerase II (RNA-POL-II) recruitment and activate gene transcription. Our study reveals a novel LSD1–GATA2 axis, which regulates human trophoblast syncytialization.


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