102 EVIDENCE FOR PRE-IMPLANTATION ORIGIN OF PLACENTAL FAILURE IN BOVINE CLONE PREGNANCIES

2009 ◽  
Vol 21 (1) ◽  
pp. 151
Author(s):  
S. Bauersachs ◽  
V. Zakhartchenko ◽  
S. E. Ulbrich ◽  
F. Sinowatz ◽  
H.-D. Reichenbach ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Donor Cell ◽  
Transcriptome Profiling ◽  
High Rate ◽  
Orphan Nuclear Receptor ◽  
Interesting Candidate ◽  
Placental Failure ◽  
Maternal Communication ◽  
And Function ◽  
Implantation Period

Placental abnormalities account for a high proportion of pregnancy loss after transfer of cloned (SCNT) bovine embryos. The high rate of pregnancy failure has been linked to the finding of abnormal placental formation and function. Because bovine SCNT embryos were shown to exhibit altered trophoblast differentiation (Arnold DR et al. 2006 Reproduction 132, 279–290), we hypothesized that placental abnormalities in bovine clone pregnancies may originate from disturbed embryo-maternal communication in the pre-implantation period. To test this hypothesis, we evaluated the response of the endometrium to SCNT v. IVF embryos. The SCNT embryos were produced from fibroblast cultures derived from 4 different fetuses to exclude specific effects of a particular donor cell culture. After SCNT or IVF, embryos were cultured under identical conditions. Two SCNT or IVF blastocysts (grade 1) were transferred per recipient heifer (Day 8 of estrous cycle). Ten days later the recipients were slaughtered, the uteri were recovered, and pregnancy was verified by the presence of at least one normally developed embryo. Endometrium samples of 9 SCNT and 10 IVF pregnancies were used for transcriptome profiling with a custom cDNA microarray (BOE array; Bauersachs S et al. 2007 J. Dairy Sci. 90, 4420–4423). In total, 58 transcripts were found to be differently abundant between endometrium samples from SCNT v. IVF pregnancies (SAM, FDR 5.24%). Interestingly, for some of them an important role in implantation and/or placentation has already been shown. NR2F2, encoding the orphan nuclear receptor superfamily member NR2F2 (COUP-TFII), was downregulated in endometrium from SCNT pregnancies (1.5-fold; P < 0.01). Uterine-specific Nr2f2 mutant mice are infertile due to implantation failure (Kurihara I et al. 2007 PLoS Genetics 3, e102). Another interesting candidate is GJA1, encoding connexin 43 (Cx43), with 1.8-fold (P < 0.001) downregulated transcript levels in SCNT pregnancies. A striking increase of stromal Cx43 has been observed in the ovine intercaruncular and caruncular endometrium during intensification of the feto-maternal contact (Gabriel et al. 2005 Placenta 25, 287–296), suggesting that reduced GJA1 mRNA expression in bovine clone pregnancies may negatively affect placentation. In view of the well-orchestrated spectrum of transcriptome changes in endometrium during the peri-attachment period (Bauersachs S et al. 2006 Reproduction 132, 319–331), these findings suggest that placental failure in bovine clone pregnancies may originate from abnormal embryo-maternal communication already in the pre- or peri-implantation period. This study was supported by the Deutsche Forschungsgemeinschaft (FOR 478).

scholarly journals Inhibition of connexin 43 expression and function in cultured rat dental pulp cells by antisense oligonucleotide

2007 ◽  
Vol 329 (2) ◽  
pp. 295-300 ◽  
Author(s):  
Chul-Kyun Chung ◽  
Takashi Muramatsu ◽  
Tomoko Uekusa ◽  
Hodaka Sasaki ◽  
Masaki Shimono
Keyword(s):  
Antisense Oligonucleotide ◽  
Dental Pulp ◽  
Connexin 43 ◽  
Dental Pulp Cells ◽  
Pulp Cells ◽  
And Function

scholarly journals Two-Step Regulation of Ad4BP/SF-1 Gene Transcription during Fetal Adrenal Development: Initiation by a Hox-Pbx1-Prep1 Complex and Maintenance via Autoregulation by Ad4BP/SF-1

2006 ◽  
Vol 26 (11) ◽  
pp. 4111-4121 ◽  
Author(s):  
Mohamad Zubair ◽  
Satoru Ishihara ◽  
Sanae Oka ◽  
Katsuzumi Okumura ◽  
Ken-ichirou Morohashi
Keyword(s):  
Adrenal Cortex ◽  
Binding Sites ◽  
Orphan Nuclear Receptor ◽  
Specific Expression ◽  
Steroidogenic Factor 1 ◽  
Tissue Specific ◽  
Adrenal Cells ◽  
Tissue Specific Expression ◽  
And Function ◽  
Intron 4

ABSTRACT The orphan nuclear receptor Ad4BP/SF-1 (adrenal 4 binding protein/steroidogenic factor 1) is essential for the proper development and function of reproductive and steroidogenic tissues. Although the expression of Ad4BP/SF-1 is specific for those tissues, the mechanisms underlying this tissue-specific expression remain unknown. In this study, we used transgenic mouse assays to examine the regulation of the tissue-specific expression of Ad4BP/SF-1. An investigation of the entire Ad4BP/SF-1 gene locus revealed a fetal adrenal enhancer (FAdE) in intron 4 containing highly conserved binding sites for Pbx-Prep, Pbx-Hox, and Ad4BP/SF-1. Transgenic assays revealed that the Ad4 sites, together with Ad4BP/SF-1, develop an autoregulatory loop and thereby maintain transcription, while the Pbx/Prep and Pbx/Hox sites initiate transcription prior to the establishment of the autoregulatory loop. Indeed, a limited number of Hox family members were found to be expressed in the adrenal primordia. Whether a true fetal-type adrenal cortex is present in mice remained controversial, and this argument was complicated by the postnatal development of the so-called X zone. Using transgenic mice with lacZ driven by the FAdE, we clearly identified a fetal adrenal cortex in mice, and the X zone is the fetal adrenal cells accumulated at the juxtamedullary region after birth.

scholarly journals Estrogen-related Receptor β (ERRβ) – Renaissance Receptor or Receptor Renaissance?

2016 ◽  
Vol 14 (1) ◽  
pp. nrs.14002 ◽  
Author(s):  
Shailaja D. Divekar ◽  
Deanna M. Tiek ◽  
Aileen Fernandez ◽  
Rebecca B. Riggins
Keyword(s):  
Alternative Splicing ◽  
Nuclear Receptor ◽  
Family Members ◽  
Structure And Function ◽  
The Other ◽  
Orphan Nuclear Receptor ◽  
Nuclear Receptor Superfamily ◽  
And Function ◽  
The Impact ◽  
Estrogen Related Receptor

Estrogen-related receptors (ERRs) are founding members of the orphan nuclear receptor (ONR) subgroup of the nuclear receptor superfamily. Twenty-seven years of study have yet to identify cognate ligands for the ERRs, though they have firmly placed ERRα (ESRRA) and ERRγ (ESRRG) at the intersection of cellular metabolism and oncogenesis. The pace of discovery for novel functions of ERRβ (ESRRB), however, has until recently been somewhat slower than that of its family members. ERRβ has also been largely ignored in summaries and perspectives of the ONR literature. Here, we provide an overview of established and emerging knowledge of ERRβ in mouse, man, and other species, highlighting unique aspects of ERRβ biology that set it apart from the other two estrogen-related receptors, with a focus on the impact of alternative splicing on the structure and function of this receptor.

Inhibitory Effects of Indomethacin on Implantation and its Related Phenomena

1996 ◽  
Vol 24 (4) ◽  
pp. 358-362 ◽  
Author(s):  
K Kanayama ◽  
H Osada ◽  
K Nariai ◽  
T Endo
Keyword(s):  
Birth Rate ◽  
Inhibitory Effect ◽  
High Rate ◽  
Control Group ◽  
Corpora Lutea ◽  
Response Relationship ◽  
Inhibitory Effects ◽  
Dose Response Relationship ◽  
Dose Dependent ◽  
Implantation Period

The dose-response relationship for the inhibitory effect of indomethacin on implantation and continuance of pregnancy was examined in four groups of rabbits administered with indomethacin (2.5, 5.0, 7.5 and 10.0 mg/kg) during the implantation period and compared with a control group. Implanted fetuses and corpora lutea were counted by laparotomy, and the number of offspring born was noted. The inhibitory effect of indomethacin on implantation was found to be dose–dependent, and the birth rate decreased in the indomethacin groups compared with the control group. As a result, even where implantation had been achieved, death of the implanted fetuses occurred at a high rate in rabbits administered with indomethacin during the implantation period.

scholarly journals Cardiomyocyte Expression of ZO-1 Is Essential for Normal Atrioventricular Conduction but Does Not Alter Ventricular Function

2020 ◽  
Vol 127 (2) ◽  
pp. 284-297 ◽  
Author(s):  
Jianlin Zhang ◽  
Kevin P. Vincent ◽  
Angela K. Peter ◽  
Matthew Klos ◽  
Hongqiang Cheng ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Optical Mapping ◽  
Physiological Role ◽  
Cardiac Conduction ◽  
Scaffolding Protein ◽  
Surface Ecg ◽  
Associated Proteins ◽  
And Function ◽  
Nodal Tissue ◽  
Intact Heart

Rationale: ZO-1 (Zonula occludens-1), a plasma membrane-associated scaffolding protein regulates signal transduction, transcription, and cellular communication. Global deletion of ZO-1 in the mouse is lethal by embryonic day 11.5. The function of ZO-1 in cardiac myocytes (CM) is largely unknown. Objective: To determine the function of CM ZO-1 in the intact heart, given its binding to other CM proteins that have been shown instrumental in normal cardiac conduction and function. Methods and Results: We generated ZO-1 CM-specific knockout (KO) mice using α-Myosin Heavy Chain-nuclear Cre (ZO-1cKO) and investigated physiological and electrophysiological function by echocardiography, surface ECG and conscious telemetry, intracardiac electrograms and pacing, and optical mapping studies. ZO-1cKO mice were viable, had normal Mendelian ratios, and had a normal lifespan. Ventricular morphometry and function were not significantly different between the ZO-1cKO versus control (CTL) mice, basally in young or aged mice, or even when hearts were subjected to hemodynamic loading. Atrial mass was increased in ZO-1cKO. Electrophysiological and optical mapping studies indicated high-grade atrioventricular (A-V) block in ZO-1cKO comparing to CTL hearts. While ZO-1-associated proteins such as vinculin, connexin 43, N-cadherin, and α-catenin showed no significant change with the loss of ZO-1, Connexin-45 and Coxsackie-adenovirus (CAR) proteins were reduced in atria of ZO-1cKO. Further, with loss of ZO-1, ZO-2 protein was increased significantly in ventricular CM in a presumed compensatory manner but was still not detected in the AV nodal myocytes. Importantly, the expression of the sodium channel protein NaV1.5 was altered in AV nodal cells of the ZO-1cKO versus CTL. Conclusions: ZO-1 protein has a unique physiological role in cardiac nodal tissue. This is in alignment with its known interaction with CAR and Cx45, and a new function in regulating the expression of NaV1.5 in AV node. Uniquely, ZO-1 is dispensable for function of the working myocardium.

scholarly journals Percutaneous Oblique Distal Osteotomy of the Fifth Metatarsal for Bunionette Correction: A Prospective Cohort Study

2020 ◽  
Vol 5 (4) ◽  
pp. 2473011420S0003
Author(s):  
Gabriel F. Ferraz ◽  
Tatiana F. Santos ◽  
Daniel Oksman ◽  
Miguel V. Pereira Filho
Keyword(s):  
Statistical Tests ◽  
High Capacity ◽  
High Rate ◽  
Personal Satisfaction ◽  
Superficial Infection ◽  
Tailor’S Bunion ◽  
Distal Osteotomy ◽  
Low Incidence ◽  
And Function ◽  
Suitable Area

Category: Lesser Toes; Midfoot/Forefoot Introduction/Purpose: Bunionette is a very common foot disorder, and several kinds of corrective surgery have been described. With the popularization of minimally invasive surgeries, the forefoot region became a suitable area for this kind of technique. The aim of this study was to evaluate the results of oblique distal osteotomy of the fifth metatarsal adapted for the percutaneous approach. Methods: We prospectively evaluated 31 consecutive tailor’s bunion patients who underwent surgical correction after failure of conservative treatment between 2016 and 2019, totaling 42 feet. Clinical outcomes such as pain (VAS), function (AOFAS), criteria of personal satisfaction, and complications were evaluated. Radiographic aspects were also included. The Shapiro and Mann- Whitney statistical tests were run in the Stats package within the R environment. Results: The average age of the patients was 69.54 years, and the average follow-up was 13.14 months. There was a decrease of 6.67 points in the VAS for pain (p<0.001) and an increase of 34.94 in AOFAS (p<0.001) after the surgical procedure. Radiographic correction was achieved at both the fifth metatarsophalangeal angle (p<0.001) and intermetatarsal angle (p<0.001), which showed decreased values. There was one case of superficial infection and two cases of nonconsolidation (asymptomatic). A large majority of patients considered the procedure outcome satisfactory. Conclusion: The percutaneous oblique distal osteotomy of the fifth metatarsal for bunionette deformity showed improvement in pain and function and a high rate of personal satisfaction with a low incidence of complications and high capacity to correct the deformity.

47 DIFFERENTIAL DEVELOPMENTAL ABILITY OF EMBRYOS CLONED FROM TISSUE-SPECIFIC STEM CELLS

2007 ◽  
Vol 19 (1) ◽  
pp. 142
Author(s):  
K. Inoue ◽  
N. Ogonuki ◽  
H. Miki ◽  
S. Noda ◽  
S. Inoue ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nuclear Transfer ◽  
Embryonic Stem ◽  
Donor Cell ◽  
Fibroblast Cell ◽  
High Rate ◽  
Full Potential ◽  
Cell Nuclei ◽  
Cell Stage

Although cloning animals by somatic cell nuclear transfer is generally an inefficient process, use of appropriate donor cell types may improve the cloning outcome significantly. Among the donor cells tested so far, mouse embryonic stem cells have given the best efficiency in terms of the development of reconstructed embryos into offspring. In this study, we examined whether 2 in vitro-produced pluripotent stem cells—neural stem cells (NSCs) and mesenchymal stem cells (MSCs)—could be better nuclear donors than other differentiated cells. Embryos were reconstructed by transfer of nuclei from NSCs or MSCs with full potential for differentiation in vitro. Most (76%) of the 2-cell NCS embryos developed to the 4-cell stage; 43% implanted and 1.6% developed to term after transfer to pseudopregnant recipients. These rates were very similar to those of embryos cloned from fibroblast cell nuclei. Interestingly, in the patterns of zygotic gene expression, NSC embryos were more similar to in vitro-fertilized embryos than fibroblast cloned embryos. By contrast, embryos reconstructed using MSC nuclei showed lower developmental ability and no implantation was obtained after embryo transfer. Chromosomal analysis of the donor MSCs revealed very high frequencies of monosomy and trisomy, which might have caused the very poor post-implantation development of embryos following nuclear transfer. Thus, in vitro-produced pluripotent cells can serve as donors of nuclei for cloning mice, but may be prone to chromosomal aberrations leading to a high rate of cloned embryo death.

scholarly journals Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation

2020 ◽  
Vol 9 (1) ◽  
pp. 266 ◽  
Author(s):  
Marsida Hutka ◽  
Lee B. Smith ◽  
Ellen Goossens ◽  
W. Hamish B. Wallace ◽  
Jan-Bernd Stukenborg ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Connexin 43 ◽  
Xenograft Model ◽  
Cell Maturation ◽  
Human Testis ◽  
Testicular Development ◽  
Future Fertility ◽  
And Function ◽  
Testis Tissue

The future fertility of prepubertal boys with cancer may be irreversibly compromised by chemotherapy and/or radiotherapy. Successful spermatogenesis has not been achieved following the xenotransplantation of prepubertal human testis tissue, which is likely due to the failure of somatic cell maturation and function. We used a validated xenograft model to identify the factors required for Leydig and Sertoli cell development and function in immature human testis. Importantly, we compared the maturation status of Sertoli cells in xenografts with that of human testis tissues (n = 9, 1 year-adult). Human fetal testis (n = 6; 14–21 gestational weeks) tissue, which models many aspects of prepubertal testicular development, was transplanted subcutaneously into castrated immunocompromised mice for ~12 months. The mice received exogenous human chorionic gonadotropin (hCG; 20IU, 3×/week). In xenografts exposed continuously to hCG, we demonstrate the maintenance of Leydig cell steroidogenesis, the acquisition of features of Sertoli cell maturation (androgen receptor, lumen development), and the formation of the blood–testis barrier (connexin 43), none of which were present prior to the transplantation or in xenografts in which hCG was withdrawn after 7 months. These studies provide evidence that hCG plays a role in Sertoli cell maturation, which is relevant for future investigations, helping them generate functional gametes from immature testis tissue for clinical application.

scholarly journals NR4A Expression by Human Marginal Zone B-Cells

Antibodies ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 50
Author(s):  
Kim Doyon-Laliberté ◽  
Josiane Chagnon-Choquet ◽  
Michelle Byrns ◽  
Matheus Aranguren ◽  
Meriam Memmi ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Population ◽  
Human Blood ◽  
Marginal Zone ◽  
Ex Vivo ◽  
Transcriptome Profiling ◽  
Marginal Zone B Cells ◽  
Healthy Donors ◽  
And Function

We have previously characterized a human blood CD19+CD1c+IgM+CD27+CD21loCD10+ innate-like B-cell population, which presents features shared by both transitional immature and marginal zone (MZ) B-cells, named herein “precursor-like” MZ B-cells. B-cells with similar attributes have been associated with regulatory potential (Breg). In order to clarify this issue and better characterize this population, we have proceeded to RNA-Seq transcriptome profiling of mature MZ and precursor-like MZ B-cells taken from the blood of healthy donors. We report that ex vivo mature MZ and precursor-like MZ B-cells express transcripts for the immunoregulatory marker CD83 and nuclear receptors NR4A1, 2, and 3, known to be associated with T-cell regulatory (Treg) maintenance and function. Breg associated markers such as CD39 and CD73 were also expressed by both populations. We also show that human blood and tonsillar precursor-like MZ B-cells were the main B-cell population to express elevated levels of CD83 and NR4A1-3 proteins ex vivo and without stimulation. Sorted tonsillar precursor-like MZ B-cells exerted regulatory activity on autologous activated CD4+ T-cells, and this was affected by a CD83 blocking reagent. We believe these observations shed light on the Breg potential of MZ populations, and identify NR4A1-3 as potential Breg markers, which as for Tregs, may be involved in stabilization of a regulatory status. Since expression and activity of these molecules can be modulated therapeutically, our findings may be useful in strategies aiming at modulation of Breg responses.

New functions for old factors: the role of polyamines during the establishment of pregnancy

2019 ◽  
Vol 31 (7) ◽  
pp. 1228
Author(s):  
Jane C. Fenelon ◽  
Bruce D. Murphy
Keyword(s):  
Molecular Mechanisms ◽  
New Technologies ◽  
Alternative Pathway ◽  
Rapid Expansion ◽  
Polyamine Synthesis ◽  
Recent Developments ◽  
And Function ◽  
Implantation Period ◽  
Synthesis Regulation

Implantation is essential for the establishment of a successful pregnancy, and the preimplantation period plays a significant role in ensuring implantation occurs in a timely and coordinated manner. This requires effective maternal–embryonic signalling, established during the preimplantation period, to synchronise development. Although multiple factors have been identified as present during this time, the exact molecular mechanisms involved are unknown. Polyamines are small cationic molecules that are ubiquitously expressed from prokaryotes to eukaryotes. Despite being first identified over 300 years ago, their essential roles in cell proliferation and growth, including cancer, have only been recently recognised, with new technologies and interest resulting in rapid expansion of the polyamine field. This review provides a summary of our current understanding of polyamine synthesis, regulation and function with a focus on recent developments demonstrating the requirements for polyamines during the establishment of pregnancy up to the implantation stage, in particular the role of polyamines in the control of embryonic diapause and the identification of an alternative pathway for their synthesis in sheep pregnancy. This, along with other novel discoveries, provides new insights into the control of the peri-implantation period in mammals and highlights the complexities that exist in regulating this critical period of pregnancy.

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