Insulinotropic nucleobindin-2/nesfatin-1 is dynamically expressed in the haemochorial mouse and human placenta

2018 ◽  
Vol 30 (3) ◽  
pp. 519 ◽  
Author(s):  
Crystalyn B. Legg-St Pierre ◽  
Martina Mackova ◽  
Ewa I. Miskiewicz ◽  
Denise G. Hemmings ◽  
Suraj Unniappan ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
Energy Homeostasis ◽  
Hormone Secretion ◽  
Giant Cells ◽  
Nutrient Sensing ◽  
Trophoblast Cells ◽  
Chorionic Villi ◽  
Capillary Endothelial Cells ◽  
A Site ◽  
Trophoblast Giant Cells

The placenta is the physiological bridge between mother and fetus and has life-sustaining functions during pregnancy, including metabolic regulation, fetal protection and hormone secretion. Nucleobindin-2 (NUCB2) is a calcium- and DNA-binding protein and precursor of nesfatin-1, a signalling peptide with multiple functions, including regulation of energy homeostasis and glucose transport. These are also key functions of the placenta, yet NUCB2/nesfatin-1 expression has never been comprehensively studied in this organ. In the present study, mouse placental samples from Embryonic Day (E) 7.5 to E17.5 and human chorionic villi from the first and second trimester, as well as term pregnancy, were analysed for NUCB2/nesfatin-1 expression by immunohistochemistry with an antiserum that recognised both NUCB2 and nesfatin-1. From E7.5 to E9.5, NUCB2/nesfatin-1 was expressed in the ectoplacental cone, then parietal trophoblast giant cells and early spongiotrophoblast. At E10.5–12.5, NUCB2/nesfatin-1 expression became detectable in the developing labyrinth. From E12.5 and onwards, NUCB2/nesfatin-1 was expressed in the glycogen trophoblast cells, as well as highly expressed in syncytiotrophoblast, sinusoidal trophoblast giant cells and fetal capillary endothelial cells of the labyrinth. In all trimesters of human pregnancy, NUCB2/nesfatin-1 was highly expressed in syncytiotrophoblast. In addition, there was a significant increase in NUCB2 expression in human primary trophoblast cells induced to syncytialise. Thus, the haemochorial mammalian placenta is a novel source of NUCB2/nesfatin-1 and likely a site of its action, with potential roles in glucose homeostasis and/or nutrient sensing.

Metalloproteinases mediate extracellular matrix degradation by cells from mouse blastocyst outgrowths

Development ◽  
1992 ◽  
Vol 114 (2) ◽  
pp. 447-456 ◽  
Author(s):  
O. Behrendtsen ◽  
C.M. Alexander ◽  
Z. Werb
Keyword(s):  
Extracellular Matrix ◽  
Giant Cells ◽  
Matrix Degradation ◽  
Trophoblast Cells ◽  
Type Iv Collagenase ◽  
Type Iv ◽  
The Matrix ◽  
Remodeling Of Extracellular Matrix ◽  
Trophoblast Giant Cells ◽  
Blocking Antibodies

The maintenance and developmental remodeling of extracellular matrix is crucial to such processes as uterine implantation and the cell migratory events of morphogenesis. When mouse blastocysts are placed in culture they adhere to extracellular matrix, and trophoblast giant cells migrate out onto the matrix and degrade it. The secretion of functional proteinases by developing mouse embryos increases dramatically at the time of implantation. By zymography we identified the major secreted gelatin-degrading proteinase, also known as type IV collagenase, as one migrating at 92 × 10(3) Mr. Several casein-degrading proteinases were also secreted. The tissue inhibitor of metalloproteinases (TIMP) inhibited all of the embryo-derived proteinases detected by gelatin gel zymography, indicating that they are metalloproteinases, whereas TIMP did not inhibit all of the caseinases. Urokinase was also secreted. Addition of TIMP at 5–500 nM effectively inhibited the degradation of matrix by the trophoblast outgrowths. Blocking antibodies directed against 92 × 10(3) Mr gelatinase abolished matrix degradation by the trophoblast cells. These observations suggest that several metalloproteinases are regulated in early development and that 92 × 10(3) Mr gelatinase, in particular, has a rate-limiting function in degradation of the maternal extracellular matrix by trophoblast cells.

scholarly journals Placental lactogen-I gene activation in differentiating trophoblast cells: extrinsic and intrinsic regulation involving mitogen-activated protein kinase signaling pathways

2000 ◽  
Vol 165 (2) ◽  
pp. 443-456 ◽  
Author(s):  
TJ Peters ◽  
BM Chapman ◽  
MW Wolfe ◽  
MJ Soares
Keyword(s):  
Growth Factor ◽  
Gene Activation ◽  
Growth Factor Receptor ◽  
Giant Cells ◽  
Mitogen Activated Protein Kinase ◽  
Placental Lactogen ◽  
Trophoblast Cells ◽  
Mitogen Activated Protein ◽  
Trophoblast Giant Cells ◽  
I Gene

Trophoblast giant cells are one of the primary endocrine cell types of the rodent placenta. Placental lactogen-I (PL-I) is the initial prolactin (PRL) family member expressed as trophoblast giant cells differentiate. In this report, we use the Rcho-1 trophoblast cell line as a model for studying the regulation of PL-I gene expression during trophoblast giant cell differentiation. Evidence is provided for trophoblast cell expression of epidermal growth factor receptor (EGFR), ErbB2, fibroblast growth factor receptor 1 (FGFR1), transforming growth factor-alpha, and heparin-binding EGF. EGF and FGF-2 stimulated PL-I mRNA and protein accumulation and PL-I promoter activity in a concentration-dependent manner. These latter growth factor actions on PL-I promoter activities were specifically inhibited by cotransfection with dominant negative constructs for EGFR and FGFRs respectively. Utilization of the mitogen-activated protein kinase (MAPK) pathway by EGF and FGF-2 in trophoblast cells was demonstrated by growth factor stimulation of a Gal4 DNA binding/Elk1 transactivational domain fusion construct, and more specifically by activation of extracellular signal regulated kinase and p38 MAPK. PL-I gene activation was also sensitive to disruption of MAPK and activation protein-1 (AP-1) signaling pathways. In conclusion, autocrine/paracrine pathways involving EGFR and FGFR1, MAPK and AP-1 are shown to participate in the regulation of the PL-I gene in differentiating trophoblast cells.

scholarly journals Localization of paternal H-2K antigens on murine trophoblast cells in vivo.

1982 ◽  
Vol 155 (6) ◽  
pp. 1679-1689 ◽  
Author(s):  
S Chatterjee-Hasrouni ◽  
P K Lala
Keyword(s):  
Uterine Artery ◽  
Giant Cells ◽  
Capillary Endothelium ◽  
Trophoblast Cells ◽  
In Vivo Expression ◽  
Trophoblast Giant Cells ◽  
Negative Controls

We have previously shown the presence of H-2K and D antigens of both parental haplotypes on dispersed murine trophoblast cells. The question still remained whether such antigens are sequestered away from the sinusoidal face of these cells making them inert as allografts. The in vivo expression of H-2 antigens on these cells was therefore examined radioautographically after perfusion of 125I-labeled monoclonal and anti-H-2Kk (anti-paternal) antibody directly into individual placental branches of the uterine artery suppling 15-d-old (C57BL/6J female) X CBA/J male) placentae. Syngeneic C57BL/6J placentae served as negative controls. A radioautographic examination of 0.5-micrometer-thick sections revealed specific labeling of labyrinthine trophoblasts lining the sinusoids of allogeneic placentae. Most of this labeling was localized to the sinusoidal face of the cells as opposed to a weak labeling of the intracellular aspect. Spongiotrophoblasts and trophoblast giant cells did not label, but specific labeling of fetal capillary endothelium and some macrophages was also noted.

scholarly journals Trophoblast differentiation in vitro: establishment and characterisation of a serum-free culture model for murine secondary trophoblast giant cells

Reproduction ◽  
2004 ◽  
Vol 128 (1) ◽  
pp. 53-71 ◽  
Author(s):  
A H K El-Hashash ◽  
S J Kimber
Keyword(s):  
Giant Cells ◽  
Placental Lactogen ◽  
Blood Group Antigens ◽  
Trophoblast Cells ◽  
Trophoblast Differentiation ◽  
Serum Free ◽  
Activator Protein ◽  
Trophoblast Giant Cells ◽  
Giant Nuclei

Differentiation of trophoblast giant cells is an early event during the process of murine embryo implantation. However, differentiation of secondary trophoblast giant cells in the rodent is still only partially understood, probably because of the lack of suitablein vitromodels and cell markers. In order to advance our understanding of trophoblast differentiation, suitablein vitromodels and markers are required to study their development. The objectives of this study were to establish and characterise a serum-freein vitromodel for murine secondary trophoblast cells. Secondary trophoblast giant cells growingin vitroand paraffin sections of day 8.5 postcoitum mouse embryos were processed for immunostaining to establish the expression of potential markers using antibodies to blood group antigens, E-cadherin, α7integrins and activator protein-γ, as well as placental lactogen-II. Within 3 days in serum-free culture, ectoplacental cone-derived secondary trophoblast cells underwent simultaneous induction of both morphological and functional differentiation. Secondary trophoblasts grewin vitroas a monolayer of cells with giant nuclei and expressed B and Le-b/Le-y blood group antigens, α7integrins and placental lactogen-II, as well as activator protein-γ. Transcripts for activator protein-γ and placental lactogen-II were detected in cultures by RT-PCR and for placental lactogen-II byin situhybridisation. At later time-points apoptosis increased. A fibronectin substrate significantly increased secondary trophoblast cell numbers and surface area of outgrowth. The increase in cells with giant nuclei coincided with induction of placental lactogen-II expression. A relationship was found between the nuclear area of secondary trophoblast cells and expression of placental lactogen-II.

scholarly journals DYNAMIC REGULATION OF AP-1 TRANSCRIPTIONAL COMPLEXES DIRECTS TROPHOBLAST DIFFERENTIATION

2015 ◽  
pp. MCB.00118-15 ◽  
Author(s):  
Kaiyu Kubota ◽  
Lindsey N. Kent ◽  
M.A Karim Rumi ◽  
Katherine F. Roby ◽  
Michael J. Soares
Keyword(s):  
Transcriptome Profiling ◽  
Giant Cells ◽  
Trophoblast Cells ◽  
Placental Development ◽  
Dynamic Regulation ◽  
In Vivo Experiments ◽  
Lineage Differentiation ◽  
Transcriptional Complexes ◽  
Trophoblast Giant Cells

Placentation is a process that establishes the maternal-fetal interface and is required for successful pregnancy. The epithelial component of the placenta consists of trophoblast cells, which possess the capacity for multi-lineage differentiation and are responsible for placental-specific functions. FOS like antigen 1 (FOSL1), a component of AP-1 transcription factor complexes, contributes to the regulation of placental development. FOSL1 expression is restricted to trophoblast giant cells and invasive trophoblast cells. In the present study, we characterized the FOSL1 regulatory pathway in rat trophoblast cells. Transcriptome profiling in control and FOSL1 knockdown cells identified FOSL1 dependent gene sets linked to endocrine and invasive functions. FOSL1 was shown to occupy AP-1 binding sites within these gene loci, determined by chromatin immunoprecipitation (ChIP). Complementary in vivo experiments using trophoblast specific-lentiviral delivery of FOSL1 shRNAs provided an in vivo validation of FOSL1 targets. FOSL1 actions require a dimerization partner. Co-immunoprecipitation, co-immunolocalization, and ChIP analyses showed that FOSL1 interacts with JUNB and to a lesser extent JUN in differentiating trophoblast cells. Knockdown of FOSL1 and JUNB expression inhibited both endocrine and invasive properties of trophoblast cells. In summary, FOSL1 recruits JUNB to form AP-1 transcriptional complexes that specifically regulate the endocrine and invasive trophoblast phenotype.

scholarly journals Phagocytosis as a potential mechanism for microbial defense of mouse placental trophoblast cells

Reproduction ◽  
2004 ◽  
Vol 128 (2) ◽  
pp. 207-218 ◽  
Author(s):  
A Amarante-Paffaro ◽  
G S Queiroz ◽  
S T Corrêa ◽  
B Spira ◽  
E Bevilacqua
Keyword(s):  
Giant Cells ◽  
Interferon Γ ◽  
Immune Defense ◽  
Trophoblast Cells ◽  
Histological Techniques ◽  
Complement Component C3 ◽  
Microbial Defense ◽  
Trophoblast Giant Cells

Trophoblast giant cells are active phagocytes during implantation and post-implantation. Phagocytosis decreases during placental maturation as the phagocytic function of nutrition is gradually replaced by the direct uptake of nutrients by the labyrinth zone trophoblast. We hypothesize that, after placental maturation, trophoblast cells maintain phagocytic functions for purposes other than nutrition. This study employs histological techniques to examine the ability of trophoblast cells to phagocytose microorganisms (yeast or bacteria)–in vivoin females receiving thioglycolate to activate macrophages andin vitroin the presence of phagocytic promoters such as interferon-γ and complement component C3. Placental trophoblast cells from the second half of gestation show basal phagocytosis that can be dramatically up-regulated by these promoters when microorganisms are inoculated into pregnant animals or introduced into culture systems. Stimulated trophoblast cells phagocytosed organisms more rapidly and in greater numbers than non-stimulated trophoblast exposed to the same numbers of organisms. Taken together, our results indicate that trophoblast cells do not lose their ability to phagocytose during the placentation process, which may imply that trophoblast cells participate in embryonic and fetal innate immune defense through elimination of microorganisms present at the maternal–fetal interface.

Metabolic Regulation of Hippocampal Neuronal Development and Its Inhibition After Irradiation

2021 ◽  
Vol 80 (5) ◽  
pp. 467-475
Author(s):  
Yu-Qing Li ◽  
C Shun Wong
Keyword(s):  
Cell Fate ◽  
Metabolic Regulation ◽  
Energy Homeostasis ◽  
Neuronal Development ◽  
Adenosine Monophosphate ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Wild Type ◽  
Newborn Neuron ◽  
Negative Effect

Abstract 5′-Adenosine monophosphate-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, plays a role in cell fate determination. Whether AMPK regulates hippocampal neuronal development remains unclear. Hippocampal neurogenesis is abrogated after DNA damage. Here, we asked whether AMPK regulates adult hippocampal neurogenesis and its inhibition following irradiation. Adult Cre-lox mice deficient in AMPK in brain, and wild-type mice were used in a birth-dating study using bromodeoxyuridine to evaluate hippocampal neurogenesis. There was no evidence of AMPK or phospho-AMPK immunoreactivity in hippocampus. Increase in p-AMPK but not AMPK expression was observed in granule neurons and subgranular neuroprogenitor cells (NPCs) in the dentate gyrus within 24 hours and persisted up to 9 weeks after irradiation. AMPK deficiency in Cre-lox mice did not alter neuroblast and newborn neuron numbers but resulted in decreased newborn and proliferating NPCs. Inhibition of neurogenesis was observed after irradiation regardless of genotypes. In Cre-lox mice, there was further loss of newborn early NPCs and neuroblasts but not newborn neurons after irradiation compared with wild-type mice. These results are consistent with differential negative effect of AMPK on hippocampal neuronal development and its inhibition after irradiation.

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