scholarly journals Mouse Model of Abortion Induced by Brucella abortus Infection

2012 ◽  
Vol 7 (3) ◽  
pp. 313-318
Author(s):  
Masahisa Watarai ◽  
Keyword(s):  
Bacterial Infection ◽  
Brucella Abortus ◽  
Bacterial Colonization ◽  
Giant Cells ◽  
Placental Development ◽  
Pregnant Mice ◽  
Ifn Γ ◽  
Bacterial Replication ◽  
And Function ◽  
Trophoblast Giant Cells

The mechanisms of abortion induced by bacterial infection are largely unknown. We found that Brucella abortus, a causative agent of brucellosis and a facultative intracellular pathogen, caused abortion in pregnant mice. High rates of abortion are observed for bacterial infection on day 4.5 of gestation, but not for other days. Regardless of whether fetuses are aborted or not, the transmission of bacteria to the fetus and bacterial replication in the placenta are observed. There is a higher degree of bacterial colonization in the placenta than in other organs and many bacteria are detected in trophoblast giant cells in the placenta. The intracellular growth-defective virB4 mutant and attenuated vaccine strain S19 do not induce abortion. In the case of abortion, the induction of IFN-γ and RANTES production is observed at day 7.5 of gestation – the placental development period – for infection by the wild type strain but not by the virB4 mutant or S19. B. abortus-infected pregnant IFN-γ knockoutmice die within 15 days of infection, but nonpregnant IFN-γ knockout mice remain alive. The neutralization of IFN-γ or RANTES, in which production is induced by infection with B. abortus serves to prevent abortion. These results indicate that abortion induced by B. abortus infection is regulated by IFN-γ during the period of placental development, and the production and function of RANTES are correlated with IFN-γ.

Placental Pathology of the Pregnant Mouse Inoculated with Brucella abortus Strain 2308

1993 ◽  
Vol 30 (2) ◽  
pp. 119-129 ◽  
Author(s):  
L. Tobias ◽  
D. O. Cordes ◽  
G. G. Schurig
Keyword(s):  
Brucella Abortus ◽  
Fetal Death ◽  
Virulent Strain ◽  
Giant Cells ◽  
Pregnant Mouse ◽  
Post Inoculation ◽  
Intracellular Replication ◽  
Visceral Yolk Sac ◽  
Pregnant Mice ◽  
Trophoblast Giant Cells

Fifty-five pregnant BALB/c mice received various doses of Brucella abortus virulent strain 2308 intraperitoneally on day 9 of gestation, and uteri and spleens were examined at 3, 5, 7, and 9 days post-inoculation to study the pathogenesis of infection. A dose of 105.7 B. abortus organisms produced a severe, necrosuppurative placentitis. Bacteria multiplied preferentially within the placenta and were identified within the rough endoplasmic reticulum of trophoblast giant cells and within the visceral yolk sac endoderm. Abortions did not occur, but infarction of the labyrinth region of severely affected placentas occasionally resulted in fetal death. The severity of infection in the spleens of nonpregnant mice receiving the same challenge dose was not significantly different from that in the spleens of challenged pregnant mice. These results suggest that the sensitivity of the pregnant mouse to placental brucellosis is not due to a generalized immunosuppression but rather may involve a combination of local suppression of the immune response and a susceptible cell population suitable for Brucella colonization and replication. Experimental murine brucellosis resembles ruminant brucellosis and provides a model to study the intracellular replication of B. abortus in trophoblasts.

scholarly journals 016.Role of cited genes in placental morphogenesis: studies in null mutant mice

2004 ◽  
Vol 16 (9) ◽  
pp. 16
Author(s):  
S. L. Dunwoodie ◽  
S. L. Withington ◽  
D. B. Sparrow ◽  
A. N. Scott ◽  
J. I. Preis ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Giant Cells ◽  
Maternal Blood ◽  
Postnatal Period ◽  
Null Mutant ◽  
Placental Development ◽  
Null Mutant Mice ◽  
And Function ◽  
Trophoblast Giant Cells ◽  
Null Mutants

Cited1 and Cited2 interact with CBP and p300. CBP/p300 bind numerous proteins and evidence exists, for Cited2 at least, that Cited binding prevents the binding of other proteins to CBP/p300. Since CBP/p300 interact with many proteins, can acetylate protein and DNA, and act as a ubiquitin ligase, it is likely that Cited1 and Cited2 function at a number of sites during development. We have generated mice that carry a null mutant allele for each of these genes. Analysis of null mutant embryos demonstrates that both Cited1 and Cited2 are required for normal embryonic development and survival. Although both Cited1 and Cited2 are expressed in the developing embryo and placenta, it appears that abnormal placental development and function is the cause of embryonic death. The defect that develops in the placentas of Cited1 null mutants is not apparent until late in gestation (16.5dpc). Cited1 null mutants are smaller than controls at birth and die during the early postnatal period. The placentas of these mutants are disorganised, with spongiotrophoblasts projecting in to the labyrinthine layer. In addition, resin casts of the maternal blood spaces within these placentas revealed extremely enlarged blood sinuses. We are searching for factors that could result in the increased size of the maternal blood sinuses. Cited2 null placentas and embryos are significantly smaller than controls; mutants die 3/4 the way through gestation (15.5dpc). The null mutant placentas have proportionally fewer spongiotrophoblasts, trophoblast giant cells and invasive trophoblasts. In addition, resin casts of fetal vasculature of the placenta reveal that the capillary network is underdeveloped. Through the isolation of trophoblast stem (TS) cells we are exploring the possibility that TS cell proliferation and/or differentiation is impaired due to a lack of Cited2. We suspect that the development of the phenotype may relate to the Hypoxia Inducible Factor-1a (HIF1a) transcription factor as Cited2 expression is induced by HIF1 and it acts to negatively regulate its activity.

scholarly journals Phosphoinositide 3-Kinase (PI3K) Subunit p110δ Is Essential for Trophoblast Cell Differentiation and Placental Development in Mouse

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiwen Hu ◽  
Jiangchao Li ◽  
Qianqian Zhang ◽  
Lingyun Zheng ◽  
Guang Wang ◽  
...  
Keyword(s):  
Fetal Death ◽  
Underlying Mechanism ◽  
Giant Cells ◽  
Placental Development ◽  
Genetic Inactivation ◽  
Chorioallantoic Placenta ◽  
Phosphoinositide 3 Kinase ◽  
Trophoblast Giant Cells ◽  
Mammalian Embryonic Development

Abstract Maternal PI3K p110δ has been implicated in smaller litter sizes in mice, but its underlying mechanism remains unclear. The placenta is an indispensable chimeric organ that supports mammalian embryonic development. Using a mouse model of genetic inactivation of PI3K p110δ (p110δD910A/D910A), we show that fetuses carried by p110δD910A/D910A females were growth retarded and showed increased mortality in utero mainly during placentation. The placentas in p110δD910A/D910A females were anomalously anemic, exhibited thinner spongiotrophoblast layer and looser labyrinth zone, which indicate defective placental vasculogenesis. In addition, p110δ was detected in primary trophoblast giant cells (P-TGC) at early placentation. Maternal PI3K p110δ inactivation affected normal TGCs generation and expansion, impeded the branching of chorioallantoic placenta but enhanced the expression of matrix metalloproteinases (MMP-2, MMP-12). Poor vasculature support for the developing fetoplacental unit resulted in fetal death or gross growth retardation. These data, taken together, provide the first in vivo evidence that p110δ may play an important role in placental vascularization through manipulating trophoblast giant cell.

211. Expression and cellular localization of HTRA3 protease during placental development in mice

2005 ◽  
Vol 17 (9) ◽  
pp. 81
Author(s):  
Y. Li ◽  
L. A. Salamonsen ◽  
G. Nie
Keyword(s):  
Blot Analysis ◽  
Cellular Localization ◽  
Giant Cells ◽  
Binding Domain ◽  
Placental Development ◽  
Mouse Uterus ◽  
Decidual Cells ◽  
Igf Binding ◽  
Near Term ◽  
And Function

Placental development in mice involves highly regulated interactions between fetal- and maternal-derived cells. We have previously cloned a novel serine protease (HtrA3) containing an insulin-like growth factor (IGF) binding domain, which was upregulated during pregnancy, especially post-implantation in the mouse uterus.1 The present study examined HtrA3 regulation during placental development in mice, in particular, its expression in the different compartments of the placenta. Expression of mRNA was determined by Northern blot analysis in implantation units containing the decidua, placenta and fetus (day 8.5 to near-term). A specific HtrA3 antibody was generated, affinity-purified and used for Western blot analysis and immunohistochemistry. Both mRNA and protein of HtrA3 were identified specifically in the maternal decidua. In contrast, HtrA3 expression was below detection in trophoblasts, including the giant cells that are in direct contact with the decidua. This pattern persisted from the early stages of placentation to near term. The level of decidual HtrA3 mRNA and its protein gradually decreased as the placenta matured. In the decidua, only the maternal decidual cells, but not blood vessels or uterine NK cells that are present in large numbers, were positive for HtrA3. The specific localization of HtrA3, a protease possessing an IGF binding domain at the maternal–fetal interface, suggests that this protein plays an important role in mediating maternal decidual remodelling and maintenance, probably in association with the IGF system, in placental development and function. (1)Nie et al. (2003). Mol. Hum. Reprod.

scholarly journals Developmental expression of the homeobox protein Distal-less 3 and its relationship to progesterone production in mouse placenta

2005 ◽  
Vol 186 (2) ◽  
pp. 315-323 ◽  
Author(s):  
K A Berghorn ◽  
P A Clark ◽  
B Encarnacion ◽  
C J DeRegis ◽  
J K Folger ◽  
...  
Keyword(s):  
Giant Cells ◽  
Late Gestation ◽  
Developmental Expression ◽  
Placental Development ◽  
Progesterone Production ◽  
Mouse Placenta ◽  
Homeobox Protein ◽  
Trophoblast Stem Cell ◽  
Trophoblast Giant Cells

Distal-less 3 (Dlx3) is a homeobox factor that functions as a placental-specific transcriptional regulator. Dlx3 null mice (−/−) have compromised placental development and do not survive in utero past embryonic day (E) 9.5. The current studies were undertaken to examine the expression of Dlx3 in mouse placenta during gestation, and to determine whether Dlx3 was involved in placental progesterone production. Dlx3 was not detectable at E8.5 but was detected in E9.5 placenta with continuing but diminished expression through E15.5. Dlx3 immuno-localization was restricted to the labyrinth, was nuclear and was found in cytokeratin-positive cells. Previous studies in choriocarcinoma cell lines support the conclusion that Dlx3 is required for expression of 3′-hydroxysteroid dehydrogenase VI (3βHSD VI), an obligate enzyme in the production of progesterone by trophoblast giant cells. In a rat trophoblast stem cell line (Rcho-1), Dlx3 expression was non-detectable in Rcho-1 cells induced to differ-entiate using mitogen withdrawal. In vitro progesterone production in placental cultures and 3βHSD VI mRNA from Dlx3 (+/+), (+/−) and (−/−) mice were equivalent. In situ hybridization for 3βHSD VI revealed mRNA expression restricted to trophoblast giants cells with no detectable expression in the labyrinth suggesting that Dlx3 and 3βHSD VI were not colocalized within the placenta. These studies support the conclusion that Dlx3 protein expression is restricted to the labyrinth region of the murine placenta into late gestation and that Dlx3 does not appear to be expressed in trophoblast giant cells. Further, loss of Dlx3 was not correlated with synthesis of progesterone from E9.5 mouse placentas.

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.

71 WHAT IS THE UTERINE RESPONSE IN A CLONED BOVINE PREGNANCY?

2006 ◽  
Vol 18 (2) ◽  
pp. 144 ◽  
Author(s):  
T. C. Santos ◽  
F. T. V. Pereira ◽  
A. C. Assis Neto ◽  
C. E. Ambrósio ◽  
F. V. Meirelles ◽  
...  
Keyword(s):  
Cell Cycle ◽  
First Trimester ◽  
Giant Cells ◽  
Differential Analysis ◽  
Placental Development ◽  
Trophoblastic Cells ◽  
M Phase ◽  
Cell Cycle Phases ◽  
Cloned Bovine ◽  
Trophoblast Giant Cells

Bovine has a synepitheliochorial placenta and characteristically there is no invasion of the trophoblast, but there is migration of the binucleate trophoblast giant cells into the maternal endometrium. The feto-maternal interface occurs in placentome where a tridimensional organization permits interactions between maternal epithelium and trophoblast, and in the intercaruncular area it is possible to observe a few mini-placentomes and the uterine glands opening. The objective of the present investigation was to study the morphological aspects of the uterus in bovine that had a cloned cattle gestations to understand the differences with natural gestation. The uterus and fetal membranes from natural and cloned cattle gestations were collected, fixed in 10% formaldehyde, processed, and stained for light microscopy and immunohistochemistry. The morphological differences observed in the surrogate uterus were: extensive areas without placentome, hemorrhagic uterine areas, caruncular fusion giving a reduced number of caruncules, increase in size and weight (megacaruncules), and a significant number of mini-caruncules giving miniplacentomes (diameter < 1 cm). In particular the mini-placentome showed functional trophoblastic cells with PAS+ granules in the binucleate trophoblast giant cells and an intense subepithelial capillary organization in maternal and fetal sides. The normal and clone placentomal cell populations were analyzed throughout pregnancy. The population of tetraploid and diploid trophoblastic cells was stained; detached cell cycle and DNA content was measured in FL2 using a FACscalibur flow cytometric system. We determined the percentage of cells in apoptosis (sub-G1), quiescent cells (G0/G1), synthesis (S), and proliferative cells (G2/M) with the aid of ModFit software. In addition, a cell cycle differential analysis was performed, and the tetraploid population presented statistical differences in cell cycle phases and populations relative to the apoptosis rate for the first (7.5 � 3.1%), second (15.2 � 5.0%) and third (17.3 � 4.3%) trimesters. The number of apoptotic cells increased significantly during pregnancy stages. The results showed that first trimester presented the majority of its cells in the G0-G1 phase, starting the cell cycle. On the other hand, the second and third trimesters presented the majority of their cells in the G2-M phase, ending the cell cycle. The relationship between cell cycle phases/rate of apoptosis in mononucleate cells, days of normal and cloned pregnancy, the number of binucleate cells, and their metabolic activity as well as their developmental kinetics could be important data in several studies that involve placental development in natural pregnancy or that derived from laboratory-manipulated embryos. This work was supported by FAPESP and CNPq.

Mrj encodes a DnaJ-related co-chaperone that is essential for murine placental development

Development ◽  
1999 ◽  
Vol 126 (6) ◽  
pp. 1247-1258 ◽  
Author(s):  
P.J. Hunter ◽  
B.J. Swanson ◽  
M.A. Haendel ◽  
G.E. Lyons ◽  
J.C. Cross
Keyword(s):  
Protein Function ◽  
Cell Types ◽  
Giant Cells ◽  
Gene Trap ◽  
Developmental Defect ◽  
Placental Development ◽  
E Coli ◽  
Mouse Tissues ◽  
Transcription Factor Genes ◽  
Trophoblast Giant Cells

We have identified a novel gene in a gene trap screen that encodes a protein related to the DnaJ co-chaperone in E. coli. The gene, named Mrj (mammalian relative of DnaJ) was expressed throughout development in both the embryo and placenta. Within the placenta, expression was particularly high in trophoblast giant cells but moderate levels were also observed in trophoblast cells of the chorion at embryonic day 8.5, and later in the labyrinth which arises from the attachment of the chorion to the allantois (a process called chorioallantoic fusion). Insertion of the ROSAbetageo gene trap vector into the Mrj gene created a null allele. Homozygous Mrj mutants died at mid-gestation due to a failure of chorioallantoic fusion at embryonic day 8.5, which precluded formation of the mature placenta. At embryonic day 8.5, the chorion in mutants was morphologically normal and expressed the cell adhesion molecule beta4 integrin that is known to be required for chorioallantoic fusion. However, expression of the chorionic trophoblast-specific transcription factor genes Err2 and Gcm1 was significantly reduced. The mutants showed no abnormal phenotypes in other trophoblast cell types or in the embryo proper. This study indicates a previously unsuspected role for chaperone proteins in placental development and represents the first genetic analysis of DnaJ-related protein function in higher eukaryotes. Based on a survey of EST databases representing different mouse tissues and embryonic stages, there are 40 or more DnaJ-related genes in mammals. In addition to Mrj, at least two of these genes are also expressed in the developing mouse placenta. The specificity of the developmental defect in Mrj mutants suggests that each of these genes may have unique tissue and cellular activities.

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