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Gcm1 placental

Dongmei Zhu, Xia Gong, Liyun Miao, Junshun Fang, Jian Zhang
The syncytiotrophoblast layer is the most critical and prominent tissue in placenta. SynT cells are differentiated from trophoblast stem cells (TSCs) during early embryogenesis. Mouse TSCs can spontaneously differentiate into cells of mixed lineages in vitro upon withdrawal of stemness-maintaining factors. However, differentiation into defined placental cell lineages remains challenging. We report here that canonical Wnt signaling activation robustly induces expression of SynT-II lineage-specific genes Gcm1 and SynB and suppresses markers of other placental lineages...
December 12, 2017: Stem Cell Reports
Xiaoyin Lu, Rui Wang, Cheng Zhu, Haibin Wang, Hai-Yan Lin, Yan Gu, James C Cross, Hongmei Wang
Many types of multinucleated cells (syncytia) generated by cell-cell fusion are post-mitotic, but it remains unclear how this state is maintained and why. Here, we utilized the fluorescent ubiquitination-based cell-cycle indicator (Fucci) reporter system to show that human placental trophoblast cells were all in the G0 phase before they fuse. Expression of the fusogenic protein (fusogen) Syncytin-2 was confined to G0 cells. Overexpression of Syncytin-2 in cycling cells overrode the cell-cycle restriction and enabled fusion of cells in the S/G2/M phases but resulted in the unstable syncytia retaining mitotic features...
October 31, 2017: Cell Reports
Maya A Deyssenroth, Qian Li, Marina Lacasaña, Yoko Nomura, Carmen Marsit, Jia Chen
The placenta is the principal organ regulating respiratory, nutritional, endocrine and metabolic functions on behalf of the developing fetus. Changes in gene expression patterns of placenta-specific genes may influence fetal growth. We profiled the expression of 17 genes related to placenta functioning in term placentas (n=677) to identify genes differentially expressed across birth weight categories [small (SGA), appropriate (AGA) and large (LGA) for gestational age]. ABCG2, CEBPB, CRH, GCM1, GPC3, INSL4, PGF and PLAC1 were inversely associated with LGA status, with odds ratios (ORs) and 95% confidence intervals (CI) ranging from GCM1 (OR=0...
October 26, 2017: Journal of Perinatal Medicine
Lauretta A Lacko, Romulo Hurtado, Samantha Hinds, Michael G Poulos, Jason M Butler, Heidi Stuhlmann
EGFL7 is a secreted angiogenic factor produced by embryonic endothelial cells. To understand its role in placental development, we established a novel Egfl7 knockout mouse. The mutant mice have gross defects in chorioallantoic branching morphogenesis and placental vascular patterning. Microangiography and 3D imaging revealed patchy perfusion of Egfl7-/- placentas marked by impeded blood conductance through sites of narrowed vessels. Consistent with poor feto-placental perfusion, Egfl7 knockout resulted in reduced placental weight and fetal growth restriction...
July 1, 2017: Development
Sha Li, Mark S Roberson
The placental transcription factors Distal-less 3 (DLX3) and Glial cell missing-1 (GCM1) have been shown to coordinate the specific regulation of PGF in human trophoblast cell lines. While both factors independently have a positive effect on PGF gene expression, when combined, DLX3 acts as an antagonist to GCM. Despite this understanding, potential mechanisms accounting for this regulatory interaction remain unexplored. We identify physical and functional interactions between specific domains of DLX3 and GCM1 in human trophoblast-derived cells by performing immunoprecipitation and mammalian one hybrid assays...
May 17, 2017: Scientific Reports
Shrey Kohli, Juliane Hoffmann, Franziska Lochmann, Paulina Markmeyer, Hanna Huebner, Fabian B Fahlbusch, Moh'd Mohanad Al-Dabet, Ihsan Gadi, Jayakumar Manoharan, Michael Löttge, Ana C Zenclussen, Anat Aharon, Benjamin Brenner, Khurrum Shahzad, Matthias Ruebner, Berend Isermann
Placental insufficiency jeopardizes prenatal development, potentially leading to intrauterine growth restriction (IUGR) and stillbirth. Surviving fetuses are at an increased risk for chronic diseases later in life. IUGR is closely linked with altered trophoblast and placental differentiation. However, due to a paucity of mechanistic insights, suitable biomarkers and specific therapies for IUGR are lacking. The transcription factor p45 NF-E2 (nuclear factor erythroid derived 2) has been recently found to regulate trophoblast differentiation in mice...
April 6, 2017: Cell Death & Disease
Sha Li, Mark S Roberson
Placental growth factor (PGF) is abundantly expressed by trophoblast cells within human placentae and is important for trophoblast development and placental vascularization. Circulating maternal serum levels of PGF are dynamically upregulated across gestation in normal pregnancies, whereas low circulating levels and placental production of PGF have been implicated in the pathogenesis of preeclampsia and other gestational diseases. However, the underlying molecular mechanism of regulating PGF expression in the human placenta remains poorly understood...
October 2017: Journal of Cellular Physiology
Hsiao-Fan Lo, Ching-Yen Tsai, Chie-Pein Chen, Liang-Jie Wang, Yun-Shien Lee, Chia-Yu Chen, Chung-Tiang Liang, Mei-Leng Cheong, Hungwen Chen
The transcription factor glial cells missing 1 (GCM1) regulates trophoblast differentiation and function during placentation. Decreased GCM1 expression is associated with pre-eclampsia, suggesting that abnormal expression of GCM1 target genes may contribute to the pathogenesis of pregnancy complications. Here we identified a novel GCM1 target gene, synapse defective 1 (SYDE1), which encodes a RhoGAP that is highly expressed in human placenta, and demonstrated that SYDE1 promotes cytoskeletal remodelling and cell migration and invasion...
February 2017: Journal of Pathology
Yixin Lin, Kristin M Bircsak, Ludwik Gorczyca, Xia Wen, Lauren M Aleksunes
Identifying regulators of placental breast cancer resistance protein (BCRP) expression is critical as downregulation of this transporter may increase exposure of the fetus to xenobiotics. Here, we sought to test whether the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) regulates BCRP expression in the placenta. To test this, human BeWo placental choriocarcinoma cells were cultured with the PPARγ agonist rosiglitazone or the PPARγ antagonist T0070907 for 24 h. Messenger RNA (mRNA) expression of syncytialization markers, GCM1 and hCGβ, as well as BCRP increased with PPARγ agonist treatment...
May 2017: Journal of Biochemical and Molecular Toxicology
Wenyang Hou, Didem P Sarikaya, Loydie A Jerome-Majewska
INTRODUCTION: Chorioallantoic fusion is essential for development of the labyrinth layer of the mouse placenta. However, events that occur after chorioallantoic attachment remain poorly described, partly due to difficulties of conducting ex vivo analysis of the placenta. Herein, we report conditions for ex vivo culture of the developing murine placenta. METHODS: Mesometrial halves of decidua containing pre-attachment chorions were cultured alone or with explants of allantoides from stage-matched controls and analyzed by confocal and immunofluorescence microscopy...
November 2016: Placenta
Baosheng Chen, Mark S Longtine, Maria Laura Costa, D Michael Nelson
Poor differentiation of trophoblasts is associated with placental dysfunction, predisposing women to multiple pregnancy disorders. Punicalagin, a prominent ellagitannin in pomegranate juice has been shown to exert anti-apoptosis and anti-oxidative effects in human trophoblasts. We hypothesized that punicalagin modulates trophoblast differentiation. We found that punicalagin-treated primary trophoblast showed reduced E-cadherin, higher Syncytin 1, more β-hCG, and increased GCM1, an upstream regulator of β-hCG...
August 2016: Placenta
Xiaoyin Lu, Yuxia He, Cheng Zhu, Hongmei Wang, Shiling Chen, Hai-Yan Lin
INTRODUCTION: The multinucleated syncytiotrophoblast (STB) is maintained and regenerated by the fusion of underlying cytotrophoblast cells (CTBs) and is responsible for a number of functions in the human placenta. Deficiencies in this structure may result in pregnancy-associated diseases. However, the detailed mechanisms underlying trophoblast syncytialization await further investigation. METHODS: The location of the transcription factor Twist1 in human placental tissues was identified by immunohistochemistry...
March 2016: Placenta
Yueh Ho Chiu, Hungwen Chen
Development of human placenta involves the invasion of trophoblast cells from anchoring villi into the maternal decidua. Placental transcription factor GCM1 regulates trophoblast cell invasion via transcriptional activation of HtrA4 gene, which encodes a serine protease enzyme. The GATA3 transcription factor regulates trophoblast cell differentiation and is highly expressed in invasive murine trophoblast giant cells. The regulation of trophoblastic invasion by GCM1 may involve novel cellular factors. Here we show that GATA3 interacts with GCM1 and inhibits its activity to suppress trophoblastic invasion...
February 22, 2016: Scientific Reports
Mei-Leng Cheong, Liang-Jie Wang, Pei-Yun Chuang, Ching-Wen Chang, Yun-Shien Lee, Hsiao-Fan Lo, Ming-Song Tsai, Hungwen Chen
Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation...
January 1, 2016: Molecular and Cellular Biology
Priyadarsini Kumar, Twanda L Thirkill, Jennifer Ji, Louise H Monte, Gordon C Douglas
Trophoblast differentiation during early placental development is critical for successful pregnancy and aberrant differentiation causes preeclampsia and early pregnancy loss. During the first trimester, cytotrophoblasts are exposed to low oxygen tension (equivalent to~2%-3% O2) and differentiation proceeds along an extravillous pathway (giving rise to invasive extravillous cytotrophoblasts) and a villous pathway (giving rise to multinucleated syncytiotrophoblast). Interstitial extravillous cytotrophoblasts invade the decidua, while endovascular extravillous cytotrophoblasts are involved in re-modelling uterine spiral arteries...
2015: PloS One
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
Szilvia Szabo, Meera Mody, Roberto Romero, Yi Xu, Katalin Karaszi, Noemi Mihalik, Zhonghui Xu, Gaurav Bhatti, Tibor Fule, Petronella Hupuczi, Tibor Krenacs, Janos Rigo, Adi L Tarca, Sonia S Hassan, Tinnakorn Chaiworapongsa, Ilona Kovalszky, Zoltan Papp, Nandor Gabor Than
Preterm preeclampsia is associated with the failure of trophoblast invasion, placental hypoxic/ischemic injury and the release of toxic substances, which promote the terminal pathway of preeclampsia. In term preeclampsia, factors yet unknown trigger the placenta to induce the terminal pathway. The contribution of the villous trophoblast to these pathologic events has not been fully elucidated. Here we aimed to study how stress and signaling pathways influence trophoblastic functions in various subforms of preeclampsia...
July 2015: Pathology Oncology Research: POR
Xi Tian, Kate Anthony, Thomas Neuberger, Francisco J Diaz
Zinc is an essential nutrient for optimal fertility, but the effects of preconception zinc deficiency on postimplantation development are not known. Female mice were fed a control or a zinc-deficient diet (ZDD) for 4-5 days before ovulation (preconception). Embryonic and/or placental development were evaluated on Days 3.5, 6.5, 10.5, 12.5, and 16.5 of pregnancy. The findings show a decrease in embryo length (31%, Day 10.5; 13%, Day 12.5; 10%, Day 16.5) and weight (23%, Day 16.5) in embryos from mothers fed a ZDD preconception...
April 2014: Biology of Reproduction
A C Holloway, A Salomon, M J Soares, V Garnier, S Raha, F Sergent, C J Nicholson, J J Feige, M Benharouga, N Alfaidy
In utero exposure to nicotine is associated with increased risk of numerous adverse fetal and neonatal outcomes, which suggests that it acts directly to affect placental development and the establishment of the fetomaternal circulation (FC). This study used both in vivo [Wistar rats treated with 1 mg/kg nicotine from 2 wk prior to mating until gestational day (GD) 15] and in vitro (RCHO-1 cell line; treated with 10(-9) to 10(-3)M nicotine) models to examine the effects of nicotine on these pathways. At GD 15, control and treated placentas were examined for the impact of nicotine on 1) trophoblast invasion, proliferation, and degree of hypoxia, 2) labyrinth vascularization, 3) expression of key genes of placental development, and 4) expression of placental angiogenic factors...
February 15, 2014: American Journal of Physiology. Endocrinology and Metabolism
Ching-Wen Chang, Mei-Leng Cheong, Geen-Dong Chang, Ming-Song Tsai, Hungwen Chen
The placental transcription factor glial cell missing 1 (GCM1) and its target gene syncytin-1 are involved in cAMP-stimulated trophoblastic fusion for syncytiotrophoblast formation. GCM1 DNA-binding activity is inhibited by sumoylation, whereas GCM1 stability is decreased by deacetylation. cAMP enhances GCM1 desumoylation through the Epac1/Rap1/CaMKI signaling cascade and CaMKI is known to down-regulate class IIa HDAC activity. In this paper, we study whether the Epac1/Rap1/CaMKI signaling cascade regulates GCM1 activity and placental cell fusion through class IIa HDACs...
November 2013: Molecular Human Reproduction
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