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Tamara Tilburgs, Torsten B Meissner, Leonardo M R Ferreira, Arend Mulder, Kiran Musunuru, Junqiang Ye, Jack L Strominger
During human pregnancy, fetal extravillous trophoblasts (EVT) play a key role in the regulation of maternal T cell and NK cell responses. EVT display a unique combination of Human Leukocyte Antigens (HLA); EVT do not express HLA-A and HLA-B, but do express HLA-C, HLA-E and HLA-G. The mechanisms establishing this unique HLA expression pattern have not been fully elucidated. The MHC class I and class II transcriptional activators NLRC5 and CIITA are expressed neither by EVT nor by the EVT model cell line JEG3, which has an MHC expression pattern identical to that of EVT...
March 7, 2017: Biology of Reproduction
Katie L Togher, Louise C Kenny, Gerard W O'Keeffe
Exposure to maternal cortisol plays a crucial role in fetal organogenesis. However, fetal overexposure to cortisol has been linked to a range of short- and long-term adverse outcomes. Normally, this is prevented by the expression of an enzyme in the placenta called 11-beta hydroxysteroid dehydrogenase type 2 (11β-HSD2) which converts active cortisol to its inactive metabolite cortisone. Placental 11β-HSD2 is known to be reduced in a number of adverse pregnancy complications, possibly through an epigenetic mechanism...
2017: International Journal of Cell Biology
Liane Jennifer Bailey, Sruthi Alahari, Andrea Tagliaferro, Martin Post, Isabella Caniggia
Preeclampsia, a serious hypertensive disorder of pregnancy, is characterized by elevated ceramide (CER) content that is responsible for heightened trophoblast cell death rates via apoptosis and autophagy. Whether trophoblast cells undergo necroptosis, a newly characterized form of regulated necrosis, and the potential role of CER in this process remain to be established. Herein, we report that exposure of both JEG3 cells and primary isolated cytotrophoblasts to C16:0 CER in conjunction with a caspase-8 inhibitor (Q-VD-OPh) promoted necroptotic cell death, as evidenced by increased expression and association of receptor-interacting protein kinases RIP1 and RIP3, as well as phosphorylation of mixed lineage kinase domain-like (MLKL) protein...
February 2, 2017: Cell Death & Disease
Jinhui Wu, Dongshuang Wang
Chemotherapy is typically used to treat choriocarcinoma. However, a small proportion of this malignancy develops resistance to common chemotherapeutic drugs such as methotrexate (MTX) and floxuridine (FUDR). This study aimed to investigate the role and its potential mechanisms of chloride intracellular channel protein 1 (CLIC1) in the development of chemoresistance in choriocarcinoma JeG3 cells. Two chemoresistant sublines were induced from their parental cell line JeG3 through intermittent exposure to MTX (named JeG3/MTX) or FUDR (named JeG3/FUDR)...
October 26, 2016: Oncology Research
Naveen K Neradugomma, Michael Z Liao, Qingcheng Mao
Opioid dependence during pregnancy is a rising concern. Maintaining addicted pregnant women on long-acting opioid receptor agonist is the most common strategy to manage drug abuse in pregnant women. Methadone (MET) and buprenorphine (BUP) are widely prescribed for opiate maintenance therapy. Norbuprenorphine (NBUP) is the primary active metabolite of BUP. These medications can cross the placenta to the fetus, leading to postpartum neonatal abstinence syndrome. Despite their use during pregnancy, little is known about the cellular changes in the placenta brought about by these drugs...
March 2017: Molecular Pharmacology
Whasun Lim, Changwon Yang, Sunwoo Park, Fuller W Bazer, Gwonhwa Song
As a major dietary flavonol, quercetin mitigates proliferation and progression of cancer due to its anti-angiogenic, anti-inflammatory, anti-oxidant, and apoptotic biological effects on cells. Although its apoptotic effects have been reported for various cancers, little is known of the functional role of quercetin in gestational choriocarcinoma. Results of the present study indicated that quercetin reduced proliferation and induced cell death in two choriocarcinoma cell lines, JAR and JEG3 cells, with an increase in the sub-G1 phase of the cell cycle...
June 2017: Journal of Cellular Physiology
M Massimiani, S Salvi, D Piccirilli, L Vecchione, S Moresi, S Ferrazzani, H Stuhlmann, L Campagnolo
INTRODUCTION: Placental development requires invasion and differentiation of trophoblast cells, together with coordinated fetal vasculogenesis and maternal vascular remodeling. During placental development, extravillous cytotrophoblasts invade the uterine spiral arteries of the decidua and myometrium. These invasive cytotrophoblasts replace the endothelial layer of the maternal spiral arteries, transforming them from high-resistance vessels into large-caliber capacitance vessels capable of adequately nourishing the fetus...
August 2016: Journal of Maternal-fetal & Neonatal Medicine
Whasun Lim, Muhah Jeong, Fuller W Bazer, Gwonhwa Song
Curcumin, a natural pigment for yellow color that originates from turmeric, is a diarylheptanoid widely studied for its anti-inflammatory, anti-angiogenic, anti-oxidant and anti-cancer effects on cells. In placental diseases including preeclampsia and preterm birth, curcumin reduces pro-inflammatory cytokines. Even though curcumin is regarded as a novel chemotherapeutic agent with strong apoptotic effects based on phenolic structure, little is known about its functional effects on choriocarcinoma. Therefore, in the present study, we investigated the chemotherapeutic effects of curcumin on choriocarcinoma cells (JAR and JEG3), which are valuable placental models...
August 31, 2016: Biology of Reproduction
Hong Cui, Jing Chen, Quan Na
Mother-to-infant transmission of hepatitis B virus (HBV) plays an important role in the chronic carrier state in China. In our studies, the response of trophoblast cell and choriocarcinoma cell to HBV infection regarding the expression of CD133-2 (AC141) was evaluated. Western blot and RT-PCR showed that a high level of CD133-2 protein and mRNA in HTR-8/SVneo cells, but a low level in JEG-3 cells. Lower proliferation and mobility, and higher apoptosis were observed in HTR-8/SVneo cells and JEG-3-CD133-2(+) cells after HBV infection than those in HTR-8-CD133-2(-) cells and JEG-3 cells...
2016: American Journal of Translational Research
Alies A van Mullem, Anja L M van Gucht, W Edward Visser, Marcel E Meima, Robin P Peeters, Theo J Visser
Transport of thyroid hormone (TH) across the plasma membrane is necessary for the genomic action of T3 mediated by its nuclear T3 receptor. MCT8 and MCT10 have been identified as important TH transporters. Mutations in MCT8 result in severe psychomotor retardation. In addition to TH transport into the cell, MCT8 and MCT10 also facilitate TH efflux from cells. Therefore, the aim of this study was to examine if MCT8 and MCT10 increase the availability of T3 for its nuclear receptor rather than generate a rapid equilibrium between cellular and serum T3...
December 5, 2016: Molecular and Cellular Endocrinology
K Kusama, R Bai, T Sakurai, H Bai, A Ideta, Y Aoyagi, K Imakawa
Interferon tau (IFNT) is the pregnancy recognition protein in all ruminants, and its expression is restricted to trophoblast cells. Interferon tau production increases as the conceptus elongates; however, its expression is downregulated soon after the initiation of conceptus attachment to the uterine epithelium. Our previous study identified that among 8 bovine IFNT genes, only 2 forms of IFNTs, IFNT2 and IFN-tau-c1, were expressed by the conceptuses during the periattachment period. To characterize whether Hippo signaling including a transcription cofactor yes-associated protein (YAP) was involved in the IFNT regulation, we examined the expression and effects of YAP and/or TEAD in human choriocarcinoma JEG3 and bovine trophoblast CT-1 cells, and in bovine conceptuses obtained from day 17, 20 or 22 pregnant animals (pregnant day 19...
October 2016: Domestic Animal Endocrinology
Leonardo M R Ferreira, Torsten B Meissner, Tarjei S Mikkelsen, William Mallard, Charles W O'Donnell, Tamara Tilburgs, Hannah A B Gomes, Raymond Camahort, Richard I Sherwood, David K Gifford, John L Rinn, Chad A Cowan, Jack L Strominger
HLA-G, a nonclassical HLA molecule uniquely expressed in the placenta, is a central component of fetus-induced immune tolerance during pregnancy. The tissue-specific expression of HLA-G, however, remains poorly understood. Here, systematic interrogation of the HLA-G locus using massively parallel reporter assay (MPRA) uncovered a previously unidentified cis-regulatory element 12 kb upstream of HLA-G with enhancer activity, Enhancer L Strikingly, clustered regularly-interspaced short palindromic repeats (CRISPR)/Cas9-mediated deletion of this enhancer resulted in ablation of HLA-G expression in JEG3 cells and in primary human trophoblasts isolated from placenta...
May 10, 2016: Proceedings of the National Academy of Sciences of the United States of America
Nele M A Bourgeois, Stijn L J Van Herck, Pieter Vancamp, Joke Delbaere, Chantal Zevenbergen, Simone Kersseboom, Veerle M Darras, Theo J Visser
Thyroid hormone (TH) transmembrane transporters are key regulators of TH availability in target cells where correct TH signaling is essential for normal development. Although the chicken embryo is a valuable model for developmental studies, the only functionally characterized chicken TH transporter so far is the organic anion transporting polypeptide 1C1 (OATP1C1). We therefore cloned the chicken L-type amino acid transporter 1 (LAT1) and the monocarboxylate transporters 8 (MCT8) and 10 (MCT10), and functionally characterized them, together with OATP1C1, in JEG3, COS1, and DF-1 cells...
June 2016: Endocrinology
Jayonta Bhattacharjee, Sruthi Alahari, Julien Sallais, Andrea Tagliaferro, Martin Post, Isabella Caniggia
INTRODUCTION: Hypoxia-inducible factor 1A (HIF1A) stability is tightly regulated by hydroxylation and ubiquitination. Emerging evidence indicates that HIF1A is also controlled by the interplay between SUMO-specific ligases, which execute protein SUMOylation, and Sentrin/SUMO-specific proteases that de-SUMOylate target proteins. Given the significance of HIF1A in the human placenta, we investigated whether placental HIF1A is subject to SUMOylation in physiological and pathological conditions...
April 2016: Placenta
Whasun Lim, Sunwoo Park, Fuller W Bazer, Gwonhwa Song
Apigenin is a flavonoid found in parsley, onions, oranges, tea, chamomile, wheat, and sprouts. It has a variety of biological properties including anti-oxidant, anti-mutagenic, anti-carcinogenic, anti-inflammatory, anti-proliferative, and anti-spasmodic effects. Based on epidemiological and case-control studies, apigenin is regarded as a novel chemotherapeutic agent against various cancer types. However, little is known about the effects of apigenin on choriocarcinoma cells. Therefore, we investigated the anti-cancer effects of apigenin on choriocarcinoma cells (JAR and JEG3) in the present study...
December 2016: Journal of Cellular Physiology
Jing Xu, Tharini Sivasubramaniyam, Yoav Yinon, Andrea Tagliaferro, Jocelyn Ray, Ori Nevo, Martin Post, Isabella Caniggia
TGFβ has been implicated in preeclampsia, but its intracellular signaling via phosphorylated mothers against decapentaplegic (SMADs) and SMAD-independent proteins in the placenta remains elusive. Here we show that TGFβ receptor-regulated SMAD2 was activated (Ser(465/467) phosphorylation) in syncytiotrophoblast and proliferating extravillous trophoblast cells of first-trimester placenta, whereas inhibitory SMAD7 located primarily to cytotrophoblast cells. SMAD2 phosphorylation decreased with advancing gestation, whereas SMAD7 expression increased and shifted to syncytiotrophoblasts toward term...
February 2016: Endocrinology
Christine M Armour, Simone Kersseboom, Grace Yoon, Theo J Visser
BACKGROUND: Mutations in the thyroid hormone (TH) transporter MCT8 have been identified as the cause for Allan-Herndon-Dudley Syndrome (AHDS), characterized by severe psychomotor retardation and altered TH serum levels. Here we report a novel MCT8 mutation identified in 4 generations of one family, and its functional characterization. METHODS: Proband and family members were screened for 60 genes involved in X-linked cognitive impairment and the MCT8 mutation was confirmed...
2015: PloS One
Zhuo Miao, Min Sun, Feng Jiang, Yuanqing Yao, Yi Li
Progesterone withdrawal signals labor in mammals. Elevated intracellular metabolism contributes to progesterone functional withdrawal through unknown mechanism, which is thought to act via progesterone receptor (PR). This study aims to investigate molecular mechanisms underlying progesterone withdrawal during pregnancy and labor. We investigated the role of 5α-reductase type I (SRD5A1) in enzymatic catalysis of progesterone and loss of PR function in a human trophoblast choriocarcinoma cell line JEG3. The PR isoform B (PR-B) was robustly expressed in JEG3 cells...
February 2016: Reproductive Sciences
Mariko Horii, Matteo Moretto-Zita, Katharine K Nelson, Yingchun Li, Mana M Parast
INTRODUCTION: Early placental development depends on the correct balance of cytotrophoblast (CTB) proliferation and differentiation, into either syncytiotrophoblast (STB) involved in nutrient/gas exchange, or invasive extravillous trophoblast (EVT) involved in establishment of blood flow to the placenta. Metastasis associated protein-3 (MTA3) is a transcriptional co-repressor known to regulate cell migration. In addition, MTA3 is reportedly decreased in preeclampsia. We set out to investigate the role of MTA3 in human trophoblast differentiation...
September 2015: Placenta
Santosh Philips, Jing Zhou, Zhigao Li, Todd C Skaar, Lang Li
INTRODUCTION: One major challenge in personalized medicine research is to identify the environmental factors that can alter drug response, and to investigate their molecular mechanisms. These environmental factors include co-medications, food, and nutrition or dietary supplements. The increasing use of dietary supplements and their potential interactions with cytochrome P450 (CYP450) enzymes is a highly significant personalized medicine research domain, because most of the drugs on the market are metabolized through CYP450 enzymes...
2015: BMC Genomics
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