scholarly journals One-Cell Zygote Transfer from Diabetic to Nondiabetic Mouse Results in Congenital Malformations and Growth Retardation in Offspring

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 466-469 ◽  
Author(s):  
Amanda Wyman ◽  
Anil B. Pinto ◽  
Rachael Sheridan ◽  
Kelle H. Moley
Keyword(s):  
Morphological Changes ◽  
Maternal Diabetes ◽  
First Trimester ◽  
Blastocyst Stage ◽  
Neural Tube Closure ◽  
Limb Deformities ◽  
Mouse Zygotes ◽  
The One ◽  
Zygote Stage

Fetuses of type 1 and 2 diabetic women experience higher incidences of malformations and fetal death as compared with nondiabetics, even when they achieve adequate glycemic control during the first trimester. We hypothesize that maternal diabetes adversely affects the earliest embryonic stage after fertilization and programs the fetus to experience these complications. To test this hypothesis, we transferred either one-cell mouse zygotes or blastocysts from either streptozotocin-induced diabetic or control mice into nondiabetic pseudopregnant female recipients. We then evaluated the fetuses at embryonic d 14.5 to assess fetal growth and the presence or absence of malformations. We found that fetuses from the diabetic mice transferred at the blastocyst stage but also as early as the one-cell zygote stage displayed significantly higher rates of malformations consistent with neural tube closure problems and abdominal wall and limb deformities. In addition, both these groups of fetuses were significantly growth retarded. To determine if this phenomenon was due to high glucose concentrations, two-cell embryos were cultured to a blastocyst stage in 52 mmd-glucose or l-glucose as an osmotic control, transferred into nondiabetic pseudopregnant mice, and examined at embryonic d 14.5. These embryos did not demonstrate any evidence of malformations, however, they did experience significantly higher rates of resorptions, lower implantation rates, and they were significantly smaller at embryonic d 14.5. In summary, exposure to maternal diabetes during oogenesis, fertilization, and the first 24 h was enough to program permanently the fetus to develop significant morphological changes.

scholarly journals Maternal Diabetes Causes Mitochondrial Dysfunction and Meiotic Defects in Murine Oocytes

2009 ◽  
Vol 94 (9) ◽  
pp. 3618-3618
Author(s):  
Qiang Wang ◽  
Ann M. Ratchford ◽  
Maggie M.-Y. Chi ◽  
Erica Schoeller ◽  
Antonina Frolova ◽  
...  
Keyword(s):  
Tricarboxylic Acid Cycle ◽  
Maternal Diabetes ◽  
Meiotic Spindle ◽  
Metabolic Dysfunction ◽  
Diabetic Mice ◽  
Abnormal Distribution ◽  
Mitochondrial Dna Copy Number ◽  
Transmission Electron ◽  
The One ◽  
Zygote Stage

The adverse effects of maternal diabetes on embryo development and pregnancy outcomes have recently been shown to occur as early as the one-cell zygote stage. The hypothesis of this study was that maternally inherited mitochondria in oocytes from diabetic mice are abnormal and thus responsible in part for this latency of developmental compromise. In ovulated oocytes from diabetic mice, transmission electron microscopy revealed an alteration in mitochondrial ultrastructure, and the quantitative analysis of mitochondrial DNA copy number demonstrated an increase. The levels of ATP and tricarboxylic acid cycle metabolites in diabetic oocytes were markedly reduced compared with controls, suggesting a mitochondrial metabolic dysfunction. Abnormal distribution of mitochondria within maturing oocytes also was seen in diabetic mice. Furthermore, oocytes from diabetic mice displayed a higher frequency of spindle defects and chromosome misalignment in meiosis, resulting in increased aneuploidy rates in ovulated oocytes. Collectively, our results suggest that maternal diabetes results in oocyte defects that are transmitted to the fetus by two routes: first, meiotic spindle and chromatin defects result in nondisjunction leading to embryonic aneuploidy; second, structural and functional abnormalities of oocyte mitochondria, through maternal transmission, provide the embryo with a dysfunctional complement of mitochondria that may be propagated during embryogenesis.

scholarly journals Maternal Diabetes Causes Mitochondrial Dysfunction and Meiotic Defects in Murine Oocytes

2009 ◽  
Vol 23 (10) ◽  
pp. 1603-1612 ◽  
Author(s):  
Qiang Wang ◽  
Ann M. Ratchford ◽  
Maggie M.-Y. Chi ◽  
Erica Schoeller ◽  
Antonina Frolova ◽  
...  
Keyword(s):  
Tricarboxylic Acid Cycle ◽  
Maternal Diabetes ◽  
Meiotic Spindle ◽  
Metabolic Dysfunction ◽  
Diabetic Mice ◽  
Abnormal Distribution ◽  
Mitochondrial Dna Copy Number ◽  
Transmission Electron ◽  
The One ◽  
Zygote Stage

Abstract The adverse effects of maternal diabetes on embryo development and pregnancy outcomes have recently been shown to occur as early as the one-cell zygote stage. The hypothesis of this study was that maternally inherited mitochondria in oocytes from diabetic mice are abnormal and thus responsible in part for this latency of developmental compromise. In ovulated oocytes from diabetic mice, transmission electron microscopy revealed an alteration in mitochondrial ultrastructure, and the quantitative analysis of mitochondrial DNA copy number demonstrated an increase. The levels of ATP and tricarboxylic acid cycle metabolites in diabetic oocytes were markedly reduced compared with controls, suggesting a mitochondrial metabolic dysfunction. Abnormal distribution of mitochondria within maturing oocytes also was seen in diabetic mice. Furthermore, oocytes from diabetic mice displayed a higher frequency of spindle defects and chromosome misalignment in meiosis, resulting in increased aneuploidy rates in ovulated oocytes. Collectively, our results suggest that maternal diabetes results in oocyte defects that are transmitted to the fetus by two routes: first, meiotic spindle and chromatin defects result in nondisjunction leading to embryonic aneuploidy; second, structural and functional abnormalities of oocyte mitochondria, through maternal transmission, provide the embryo with a dysfunctional complement of mitochondria that may be propagated during embryogenesis.

scholarly journals Quotienting the delay monad by weak bisimilarity

2017 ◽  
Vol 29 (1) ◽  
pp. 67-92 ◽  
Author(s):  
JAMES CHAPMAN ◽  
TARMO UUSTALU ◽  
NICCOLÒ VELTRI
Keyword(s):  
Computer Science ◽  
Equivalence Relation ◽  
Type Theory ◽  
Partial Functions ◽  
Homotopy Type Theory ◽  
Inductive Type ◽  
Alternative Approach ◽  
The One ◽  
Axiom Of Countable Choice

The delay datatype was introduced by Capretta (Logical Methods in Computer Science, 1(2), article 1, 2005) as a means to deal with partial functions (as in computability theory) in Martin-Löf type theory. The delay datatype is a monad. It is often desirable to consider two delayed computations equal, if they terminate with equal values, whenever one of them terminates. The equivalence relation underlying this identification is called weak bisimilarity. In type theory, one commonly replaces quotients with setoids. In this approach, the delay datatype quotiented by weak bisimilarity is still a monad–a constructive alternative to the maybe monad. In this paper, we consider the alternative approach of Hofmann (Extensional Constructs in Intensional Type Theory, Springer, London, 1997) of extending type theory with inductive-like quotient types. In this setting, it is difficult to define the intended monad multiplication for the quotiented datatype. We give a solution where we postulate some principles, crucially proposition extensionality and the (semi-classical) axiom of countable choice. With the aid of these principles, we also prove that the quotiented delay datatype delivers free ω-complete pointed partial orders (ωcppos).Altenkirch et al. (Lecture Notes in Computer Science, vol. 10203, Springer, Heidelberg, 534–549, 2017) demonstrated that, in homotopy type theory, a certain higher inductive–inductive type is the free ωcppo on a type X essentially by definition; this allowed them to obtain a monad of free ωcppos without recourse to a choice principle. We notice that, by a similar construction, a simpler ordinary higher inductive type gives the free countably complete join semilattice on the unit type 1. This type suffices for constructing a monad, which is isomorphic to the one of Altenkirch et al. We have fully formalized our results in the Agda dependently typed programming language.

scholarly journals Estrogens and Spermiogenesis: New Insights from Type 1 Cannabinoid Receptor Knockout Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Giovanna Cacciola ◽  
Teresa Chioccarelli ◽  
Silvia Fasano ◽  
Riccardo Pierantoni ◽  
Gilda Cobellis
Keyword(s):  
Cannabinoid Receptor ◽  
Morphological Changes ◽  
Terminal Differentiation ◽  
Environmental Chemicals ◽  
Complex Mechanism ◽  
Autocrine Factors ◽  
Estrogenic Effects ◽  
Male Gametes ◽  
Type 1 Cannabinoid Receptor

Spermatogenesis is a complex mechanism which allows the production of male gametes; it consists of mitotic, meiotic, and differentiation phases. Spermiogenesis is the terminal differentiation process during which haploid round spermatids undergo several biochemical and morphological changes, including extensive remodelling of chromatin and nuclear shape. Spermiogenesis is under control of endocrine, paracrine, and autocrine factors, like gonadotropins and testosterone. More recently, emerging pieces of evidence are suggesting that, among these factors, estrogens may have a role. To date, this is a matter of debate and concern because of the agonistic and antagonistic estrogenic effects that environmental chemicals may have on animal and human with damaging outcome on fertility. In this review, we summarize data which fuel this debate, with a particular attention to our recent results, obtained using type 1 cannabinoid receptor knockout male mice as animal model.

Capillary Microscopic and Rheological Dimensions for the Diagnosis of von Willebrand Disease in Comparison to other Haemorrhagic Diatheses

2000 ◽  
Vol 84 (12) ◽  
pp. 981-988 ◽  
Author(s):  
Reinhard Latza ◽  
Stefan Mürsdorf ◽  
Christof Mrowietz ◽  
Holger Kiesewetter ◽  
Ernst Wenzel ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Dynamic Change ◽  
Plasma Viscosity ◽  
Von Willebrand Disease ◽  
Severe Haemophilia ◽  
Capillary Microscopy ◽  
Haemorrhagic Diathesis ◽  
High Specifity ◽  
Von Willebrand

SummaryIt is known that angiodysplasia influence macrocirculation as well as microcirculation in patients with vWD. In the present study it was examined if intravital capillary microscopic dimensions (morphologic and dynamic) in skin (nailfold) in combination with rheologic parameters could give indications for the presence of vWD in patients with haemorrhagic diathesis.Patients with vWD (n = 100; 92 type 1: definite type 1:78 and possible type 1:14; 8 type 2A) have in comparison to patients with other haemorrhagic diathesis [thrombocytopathy (n = 122), thrombocytopenia (n = 101), severe haemophilia A (n = 50) and severe haemophilia B (n = 20), congenital dysfibrinogenaemia (n = 22), oral anticoagulation with phenprocoumone (n = 112)] and to apparently healthy subjects (n = 100) a significantly increased capillary torquation (median index: 3.5), a venolar and an arteriolar capillary dilatation (median: 16.5 µm; median: 15.1 µm) and the highest part of microscopic bleedings (extravasates) with 40% in the video capillary microscopy as morphological changes. Only the congenital dysfibrinogenaemia appears with a larger dilatation in venolar capillaries (median: 14.5 µm). Microscopic bleedings are much less common in other haemorrhagic diatheses with a frequency between 4% and 13%.In the vWD a significantly reduced duration of reactive hyperaemia (median: 150 sec). This is the only dynamic change that can be taken as a possible hint for a loss of flexibility within the precapillary vessels. A significantly reduced plasma viscosity (< 1.25 mPas) is typical for the vWD due to the increase of the shear stress in blood plasma because of the reduction of vWF-activities. Changes of the capillary morphology (dilatation, extravasates, capillary torquation) and the hypoplasmaviscosity are most sensitive for the vWD (75%, 65%, 40%, 80%) with a fairly high specifity (up to 93%) and a positive predictive value of 99%.As a conclusion it seems reasonable to discuss the introduction of video capillary microscopy as a screening test for haemostasiological and angiological centers.

Mouse one-cell embryos undergoing a radiation-induced G2 arrest may re-enter S-phase in the absence of cytokinesis

2002 ◽  
Vol 80 (7) ◽  
pp. 618-624 ◽  
Author(s):  
P Jacquet ◽  
J Buset ◽  
J Vankerkom ◽  
S Baatout ◽  
L de Saint-Georges ◽  
...  
Keyword(s):  
Calyculin A ◽  
Embryonic Cells ◽  
G2 Arrest ◽  
Cell Stage ◽  
Chromosome Fragments ◽  
X Irradiation ◽  
Radiation Induced ◽  
Mouse Zygotes ◽  
The One

PCC (premature chromosome condensation) can be used for visualizing and scoring damage induced by radiation in the chromatin of cells undergoing a G1 or G2 arrest. A method involving the fusion of irradiated single embryonic cells with single MI oocytes was used to induce PCC in mouse zygotes of the BALB/c strain, which suffer a drastic G2 arrest after X-irradiation (dose used 2.5 Gy). Other G2-arrested embryos were exposed in vitro to the phosphatase inhibitor calyculin A. Both methods furnished excellent chromosome preparations of the G2-arrested embryos. The mean number of chromosome fragments did not change significantly during G2 arrest, suggesting that zygotes of this strain are unable to repair DNA damage leading to such aberrations. Forty to fifty percent of the irradiated embryos were unable to cleave after G2 arrest and remained blocked at the one-cell stage for a few days before dying. PCC preparations obtained from such embryos suggested that about 30% of them had undergone a late mitosis not followed by cytokinesis and had entered a new DNA synthesis. These results are discussed in the light of recent observations in irradiated human cells deficient in the p53/14-3-3sigma pathway.Key words: PCC, embryo, oocyte, calyculin A, G2 arrest, cytokinesis.

About morphological changes in the kidney in children with infections and some other diseases

1930 ◽  
Vol 26 (2) ◽  
pp. 121-132
Author(s):  
Yu. V. Makarov
Keyword(s):  
Scarlet Fever ◽  
Morphological Changes ◽  
The Other ◽  
Histological Changes ◽  
Other Hand ◽  
Renal Changes ◽  
The One

The issue of pathological and histological changes in the kidneys in children with various infections and other diseases cannot be considered sufficiently researched and worked out. Only in certain infections (scarlet fever) has much attention been paid to the study of the kidneys. Most of the works on the issue of interest to us date back to the time when, on the one hand, insufficient importance was attached to the early dissection of corpses and the freshness of the material, which, as is now known, is of particular importance for the histology of the kidney, on the other hand, such interpretation of the detected changes, which do not correspond to the views and concepts of modern nephropathology; Finally, those changes in views on some diseases that have occurred to date, for example, in the issue of disorders of digestion and nutrition in infants, dictate the need for a different approach to the study of renal changes in these diseases.

MEK/ERK pathway mediates cell-shape-dependent plasminogen activator inhibitor type 1 gene expression upon drug-induced disruption of the microfilament and microtubule networks

2002 ◽  
Vol 115 (15) ◽  
pp. 3093-3103 ◽  
Author(s):  
Rohan Samarakoon ◽  
Paul J. Higgins
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Plasminogen Activator ◽  
Cell Shape ◽  
Morphological Changes ◽  
Signaling Events ◽  
Erk Activity ◽  
Kinetics Of ◽  
Pai 1

Changes in cellular morphology induced as a consequence of direct perturbation of cytoskeletal structure with network-specific targeting agents(i.e. microfilament- or microtubule-disrupting drugs) results in the stimulated expression of a specific subset of genes. Transcription of c-fos, collagenase, transforming growth factor-β, actin,urokinase plasminogen activator and its type-1 inhibitor (PAI-1) appears to be particularly responsive to shape-activated signaling pathways. Cytochalasin D(CD) or colchicine treatment of contact-inhibited and serum-deprived vascular smooth muscle (R22) cells was used, therefore, as a model system to evaluate morphology-associated controls on PAI-1 gene regulation in the absence of added growth factors. PAI-1 transcript levels in quiescent R22 cells increased rapidly and in a CD-concentration-dependent fashion, with kinetics of expression paralleling the morphological changes. Colchicine concentrations that effectively disrupted microtubule structure and reduced the cellular`footprint' area (to approximately that of CD treatment) also stimulated PAI-1 synthesis. Shape-related increases in PAI-1 mRNA synthesis were ablated by prior exposure to actinomycin D. Unlike the mechanism of induction in growth-factor-stimulated cells, CD- and colchicine-induced PAI-1 expression required on-going protein synthesis (i.e. it was a secondary response). Although PAI-1 is a TGF-β-regulated gene and TGF-β expression is also shape dependent, an autocrine TGF-β loop was not a factor in CD-initiated PAI-1 transcription. Since CD exposure resulted in actin microfilament disruption and subsequent morphological changes, with uncertain effects on interactions between signaling intermediates or `scaffold'structures, a pharmacological approach was selected to probe the pathways involved. Signaling events leading to PAI-1 induction were compared with colchicine-treated cells. CD- as well as colchicine-stimulated PAI-1 expression was effectively and dose dependently attenuated by the MEK inhibitor PD98059 (in the 10 to 25 μM concentration range), consistent with the known MAP kinase dependency of PAI-1 synthesis in growth-factor-stimulated cells. Reduced PAI-1 mRNA levels upon exposure to genistein prior to CD addition correlated with inhibition of ERK1/2 activity, implicating a tyrosine kinase in shape-dependent MEK activation. Src-family kinases,moreover, appeared to be specific upstream elements in the CD- and colchicine-dependent pathways of PAI-1 transcription since both agents effectively activated pp60c-src kinase activity in quiescent R22 cells. The restrictive (src-family) kinase inhibitor PP1 completely inhibited induced, as well as basal, ERK activity in a coupled immunoprecipitation myelin-basic-protein-phosphorylation assay and ablated shape-initiated PAI-1 mRNA expression. These data suggest that PP1-sensitive tyrosine kinases are upstream intermediates in cell-shape-associated signaling pathways resulting in ERK1/2 activation and subsequent PAI-1 transcription. In contrast to the rapid and transient kinetics of ERK activity typical of serum-stimulated cells, the ERK1/2 response to CD and colchicine is both delayed and relatively sustained. Collectively, these data support a model in which MEK is a focal point for the convergence of shape-initiated signaling events leading to induced PAI-1 transcription.

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