scholarly journals Placental mobilization of free fatty acids contributes to altered materno-fetal transfer in obesity

2021 ◽  
Author(s):  
Birgit Hirschmugl ◽  
Simone Perazzolo ◽  
Bram G. Sengers ◽  
Rohan M. Lewis ◽  
Michael Gruber ◽  
...  
Keyword(s):  
Plasma Lipids ◽  
Placental Transfer ◽  
Ex Vivo ◽  
Metabolic Changes ◽  
Tissue Storage ◽  
Prepregnancy Obesity ◽  
Bidirectional Exchange ◽  
The Impact ◽  
The Mathematical Model ◽  
Human Placentae

Abstract Background Metabolic changes in obese pregnant women, such as changes of plasma lipids beyond physiological levels, may subsequently affect fetal development in utero. These metabolic derangements may remain in the offspring and continue throughout life. The placenta mediates bidirectional exchange of nutrients between mother and fetus. The impact of prepregnancy obesity on placental transfer of lipids is still unknown. Objective We aimed to examine materno-to-fetal free fatty acid (FFA) transfer by a combined experimental and modeling approach. Flux of 13C-labeled FFA was evaluated by ex vivo perfusion of human placentae as a function of prepregnancy obesity. Mathematical modeling complemented ex vivo results by providing FFA kinetic parameters. Results Obesity was strongly associated with elevated materno-to-fetal transfer of applied 13C-FFA. Clearance of polyunsaturated 13C-docosahexaenoic acid (DHA) was most prominently affected. The use of the mathematical model revealed a lower tissue storage capacity for DHA in obese compared with lean placentae. Conclusion Besides direct materno-to-fetal FFA transfer, placental mobilization accounts for the fetal FA supply. Together, with metabolic changes in the mother and an elevated materno-fetal FFA transfer shown in obesity, these changes suggest that they may be transmitted to the fetus, with yet unknown consequences.

scholarly journals Plasma proteins facilitates placental transfer of polystyrene particles

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Michael M. Gruber ◽  
Birgit Hirschmugl ◽  
Natascha Berger ◽  
Magdalena Holter ◽  
Snježana Radulović ◽  
...  
Keyword(s):  
Human Plasma ◽  
Human Placenta ◽  
Plasma Proteins ◽  
Placental Transfer ◽  
Ex Vivo ◽  
Biological Fluids ◽  
Protein Corona ◽  
Human Albumin ◽  
Placental Perfusion ◽  
The Impact

Abstract Background Nanoparticles, which are exposed to biological fluids are rapidly interacting with proteins and other biomolecules forming a corona. In addition to dimension, charge and material the distinct protein corona influences the interplay of nanoparticles with tissue barriers. In this study we were focused on the impact of in situ formed human plasma protein corona on the transfer of 80 nm polystyrene nanoparticles (PS-particles) across the human placenta. To study materno-to fetal PS transfer we used the human ex vivo placental perfusion approach, which represents an intact and physiological tissue barrier. To analyze the protein corona of PS particles we performed shotgun proteomics of isolated nanoparticles before and after tissue exposure. Results Human plasma incubated with PS-particles of 80 nm and subsequent formed protein corona enhanced the transfer across the human placenta compared to PS-corona formed by bovine serum albumin and dextran which served as a control. Quantitative and qualitative changes of plasma proteins determined the changes in PS transfer across the barrier. Based on the analysis of the PS-proteome two candidate proteins, namely human albumin and immunoglobulin G were tested if these proteins may account for the enhanced PS-transfer across the placenta. Interestingly, the protein corona formed by human albumin significantly induced the transfer of PS-particles across the tissue compared to the formed IgG-corona. Conclusion In total we demonstrate the PS corona dynamically and significantly evolves upon crossing the human placenta. Thus, the initial composition of PS particles in the maternal circulation is not predictive for their transfer characteristics and performance once beyond the barrier of the placenta. The precise mechanism of these effects remains to be elucidated but highlights the importance of using well designed biological models when testing nanoparticles for biomedical applications.

Methodological Approaches to Evaluate Fetal Drug Exposure

2019 ◽  
Vol 25 (5) ◽  
pp. 496-504 ◽  
Author(s):  
Naïm Bouazza ◽  
Frantz Foissac ◽  
Déborah Hirt ◽  
Saïk Urien ◽  
Sihem Benaboud ◽  
...  
Keyword(s):  
Cord Blood ◽  
Drug Exposure ◽  
Placental Transfer ◽  
Ex Vivo ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Pbpk Models ◽  
Drug Concentrations ◽  
Fetal Drug Exposure

Background: Drug prescriptions are usual during pregnancy, however, women and their fetuses still remain an orphan population with regard to drugs efficacy and safety. Most xenobiotics diffuse through the placenta and some of them can alter fetus development resulting in structural abnormalities, growth or functional deficiencies. Methods: To summarize the different methodologies developed towards the prediction of fetal drug exposure. Results: Neonatal cord blood concentration is the most specific measurement of the transplacental drug transfer at the end of pregnancy. Using the cord blood and mother drug concentrations altogether, drug exchanges between the mother and fetus can be modeled and quantified via a population pharmacokinetic analysis. Thereafter, it is possible to estimate the fetus exposure and the fetus-to-mother exposure ratio. However, the prediction of placental transfer before any administration to pregnant women is desirable. Animal studies remain difficult to interpret due to structural and functional inter-species placenta differences. The ex-vivo perfusion of the human placental cotyledon is the method of reference to study the human placental transfer of drugs because it is thought to mimic the functional placental tissue. However, extrapolation of data to in vivo situation remains difficult. Some research groups have extensively worked on physiologically based models (PBPK) to predict fetal drug exposure and showed very encouraging results. Conclusion: PBPK models appeared to be a very promising tool in order to predict fetal drug exposure in-silico. However, these models mainly picture the end of pregnancy and knowledge regarding both, development of the placental permeability and transporters is strongly needed.

scholarly journals 231 Impact of Brachyspira hyodysentariae on intestinal function and integrity

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 116-116
Author(s):  
Emma T Helm ◽  
Susanne J Lin ◽  
Nicholas Gabler ◽  
Eric R Burrough
Keyword(s):  
Ex Vivo ◽  
Potato Starch ◽  
Nutrient Digestibility ◽  
High Morbidity ◽  
Post Inoculation ◽  
Intestinal Function ◽  
Treatment Groups ◽  
Intestinal Integrity ◽  
Beet Pulp ◽  
The Impact

Abstract Swine dysentery (SD) induced by Brachyspira hyodysentariae (Bhyo) causes colitis and mucohemorrhagic diarrhea in grow-finish pigs, however little is known about the physiological changes that occur to the gastrointestinal tract during Bhyo infection. Thus, the objective of this study was to evaluate the impact of a Bhyo challenge on intestinal function and integrity of pigs fed two divergent diets. A total of 36 Bhyo negative gilts (24.3 ± 3.6 kg BW) were selected and assigned to one of three treatment groups (n=12 pigs/trt): 1) Bhyo negative, 20% DDGS diet (CON), 2) Bhyo challenged, 20% DDGS diet (DDGS), and 3) Bhyo challenged, 10% DDGS, 5% beet pulp and 5% resistant potato starch diet (RS). Pigs were fed diets 21 days prior to challenge and on days post inoculation (dpi) 0 and 1, pigs were inoculated with Bhyo or sham. Fecal samples were collected for ATTD and pigs were euthanized for colon collection within 72 hours of initial observation of clinical SD, or at the end of the study (dpi 10-16). Tissues were assessed for ex vivo measures of intestinal integrity and mitochondrial function. The challenge resulted in high morbidity, with 88% of DDGS and RS pigs developing clinical SD. Colon transepithelial resistance was increased in DDGS pigs compared with CON and RS pigs (P=0.005), and colon macromolecule permeability was reduced in both DDGS and RS pigs compared with CON pigs (P=0.006), likely due to mucoid discharge. Colonic mitochondrial oxygen consumption was not impacted by treatment (P >0.10). Further, ATTD of DM, OM, N, and GE were reduced in DDGS pigs compared with CON pigs (P< 0.001), whilst nutrient digestibility was not reduced in RS pigs. Taken together, these data show Bhyo does not appear to reduce ex vivo colonic integrity. Further, the RS diet may reduce severity of a Bhyo challenge.

scholarly journals Histological, Biomechanical, and Biological Properties of Genipin-Crosslinked Decellularized Peripheral Nerves

2021 ◽  
Vol 22 (2) ◽  
pp. 674
Author(s):  
Óscar Darío García-García ◽  
Marwa El Soury ◽  
David González-Quevedo ◽  
David Sánchez-Porras ◽  
Jesús Chato-Astrain ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Nerve Repair ◽  
Wistar Rat ◽  
Biomechanical Properties ◽  
Biological Properties ◽  
Suitable Alternative ◽  
Promising Alternative ◽  
Histological Pattern ◽  
The Impact

Acellular nerve allografts (ANGs) represent a promising alternative in nerve repair. Our aim is to improve the structural and biomechanical properties of biocompatible Sondell (SD) and Roosens (RS) based ANGs using genipin (GP) as a crosslinker agent ex vivo. The impact of two concentrations of GP (0.10% and 0.25%) on Wistar rat sciatic nerve-derived ANGs was assessed at the histological, biomechanical, and biocompatibility levels. Histology confirmed the differences between SD and RS procedures, but not remarkable changes were induced by GP, which helped to preserve the nerve histological pattern. Tensile test revealed that GP enhanced the biomechanical properties of SD and RS ANGs, being the crosslinked RS ANGs more comparable to the native nerves used as control. The evaluation of the ANGs biocompatibility conducted with adipose-derived mesenchymal stem cells cultured within the ANGs confirmed a high degree of biocompatibility in all ANGs, especially in RS and RS-GP 0.10% ANGs. Finally, this study demonstrates that the use of GP could be an efficient alternative to improve the biomechanical properties of ANGs with a slight impact on the biocompatibility and histological pattern. For these reasons, we hypothesize that our novel crosslinked ANGs could be a suitable alternative for future in vivo preclinical studies.

scholarly journals Gut-Ex-Vivo system as a model to study gluten response in celiac disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Mara Gagliardi ◽  
Nausicaa Clemente ◽  
Romina Monzani ◽  
Luca Fusaro ◽  
Eleonora Ferrari ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Intestinal Epithelium ◽  
Complex Disease ◽  
Ex Vivo ◽  
Dynamic Condition ◽  
Model Systems ◽  
In Vivo Models ◽  
Effective Manner ◽  
Junction Protein ◽  
The Impact

AbstractCeliac disease (CD) is a complex immune-mediated chronic disease characterized by a consistent inflammation of the gastrointestinal tract induced by gluten intake in genetically predisposed individuals. Although initiated by the interaction between digestion-derived gliadin, a gluten component, peptides, and the intestinal epithelium, the disorder is highly complex and involving other components of the intestine, such as the immune system. Therefore, conventional model systems, mainly based on two- or three-dimension cell cultures and co-cultures, cannot fully recapitulate such a complex disease. The development of mouse models has facilitated the study of different interacting cell types involved in the disorder, together with the impact of environmental factors. However, such in vivo models are often expensive and time consuming. Here we propose an organ ex vivo culture (gut-ex-vivo system) based on small intestines from gluten-sensitive mice cultivated in a dynamic condition, able to fully recapitulate the biochemical and morphological features of the mouse model exposed to gliadin (4 weeks), in 16 h. Indeed, upon gliadin exposure, we observed: i) a down-regulation of cystic fibrosis transmembrane regulator (CFTR) and an up-regulation of transglutaminase 2 (TG2) at both mRNA and protein levels; ii) increased intestinal permeability associated with deregulated tight junction protein expression; iii) induction and production of pro-inflammatory cytokines such as interleukin (IL)-15, IL-17 and interferon gamma (IFNγ); and iv) consistent alteration of intestinal epithelium/villi morphology. Altogether, these data indicate that the proposed model can be efficiently used to study the pathogenesis of CD, test new or repurposed molecules to accelerate the search for new treatments, and to study the impact of the microbiome and derived metabolites, in a time- and cost- effective manner.

scholarly journals Cell–cell coupling and DNA methylation abnormal phenotypes in the after-hours mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Federico Tinarelli ◽  
Elena Ivanova ◽  
Ilaria Colombi ◽  
Erica Barini ◽  
Edoardo Balzani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Neuronal Networks ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Neuronal Cultures ◽  
Functional Impairments ◽  
After Hours ◽  
The Impact

Abstract Background DNA methylation has emerged as an important epigenetic regulator of brain processes, including circadian rhythms. However, how DNA methylation intervenes between environmental signals, such as light entrainment, and the transcriptional and translational molecular mechanisms of the cellular clock is currently unknown. Here, we studied the after-hours mice, which have a point mutation in the Fbxl3 gene and a lengthened circadian period. Methods In this study, we used a combination of in vivo, ex vivo and in vitro approaches. We measured retinal responses in Afh animals and we have run reduced representation bisulphite sequencing (RRBS), pyrosequencing and gene expression analysis in a variety of brain tissues ex vivo. In vitro, we used primary neuronal cultures combined to micro electrode array (MEA) technology and gene expression. Results We observed functional impairments in mutant neuronal networks, and a reduction in the retinal responses to light-dependent stimuli. We detected abnormalities in the expression of photoreceptive melanopsin (OPN4). Furthermore, we identified alterations in the DNA methylation pathways throughout the retinohypothalamic tract terminals and links between the transcription factor Rev-Erbα and Fbxl3. Conclusions The results of this study, primarily represent a contribution towards an understanding of electrophysiological and molecular phenotypic responses to external stimuli in the Afh model. Moreover, as DNA methylation has recently emerged as a new regulator of neuronal networks with important consequences for circadian behaviour, we discuss the impact of the Afh mutation on the epigenetic landscape of circadian biology.

scholarly journals The Impact of Elongation on Change in Electrical Resistance of Electrically Conductive Yarns Woven into Fabric

Materials ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3390
Author(s):  
Željko Knezić ◽  
Željko Penava ◽  
Diana Šimić Penava ◽  
Dubravko Rogale
Keyword(s):  
Mathematical Model ◽  
Electrical Resistance ◽  
Electrically Conductive ◽  
Textile Materials ◽  
Measurement Results ◽  
Conductive Yarns ◽  
Yarn Count ◽  
As Relationship ◽  
The Impact ◽  
The Mathematical Model

Electrically conductive yarns (ECYs) are gaining increasing applications in woven textile materials, especially in woven sensors suitable for incorporation into clothing. In this paper, the effect of the yarn count of ECYs woven into fabric on values of electrical resistance is analyzed. We also observe how the direction of action of elongation force, considering the position of the woven ECY, effects the change in the electrical resistance of the electrically conductive fabric. The measurements were performed on nine different samples of fabric in a plain weave, into which were woven ECYs with three different yarn counts and three different directions. Relationship curves between values of elongation forces and elongation to break, as well as relationship curves between values of electrical resistance of fabrics with ECYs and elongation, were experimentally obtained. An analytical mathematical model was also established, and analysis was conducted, which determined the models of function of connection between force and elongation, and between electrical resistance and elongation. The connection between the measurement results and the mathematical model was confirmed. The connection between the mathematical model and the experimental results enables the design of ECY properties in woven materials, especially textile force and elongation sensors.

scholarly journals Towards Transabdominal Functional Photoacoustic Imaging of the Placenta: Improvement in Imaging Depth Through Optimization of Light Delivery

2021 ◽  
Author(s):  
Kristie Huda ◽  
Kenneth F. Swan ◽  
Cecilia T. Gambala ◽  
Gabriella C. Pridjian ◽  
Carolyn L. Bayer
Keyword(s):  
Delivery System ◽  
Light Propagation ◽  
Ex Vivo ◽  
Photoacoustic Imaging ◽  
Incidence Angle ◽  
Incident Angle ◽  
Placental Tissue ◽  
Light Delivery ◽  
Imaging Depth ◽  
The Impact

AbstractFunctional photoacoustic imaging of the placenta could provide an innovative tool to diagnose preeclampsia, monitor fetal growth restriction, and determine the developmental impacts of gestational diabetes. However, transabdominal photoacoustic imaging is limited in imaging depth due to the tissue’s scattering and absorption of light. The aim of this paper was to investigate the impact of geometry and wavelength on transabdominal light delivery. Our methods included the development of a multilayer model of the abdominal tissue and simulation of the light propagation using Monte Carlo methods. A bifurcated light source with varying incident angle of light, distance between light beams, and beam area was simulated to analyze the effect of light delivery geometry on the fluence distribution at depth. The impact of wavelength and the effects of variable thicknesses of adipose tissue and muscle were also studied. Our results showed that the beam area plays a major role in improving the delivery of light to deep tissue, in comparison to light incidence angle or distance between the bifurcated fibers. Longer wavelengths, with incident fluence at the maximum permissible exposure limit, also increases fluence within deeper tissue. We validated our simulations using a commercially available light delivery system and ex vivo human placental tissue. Additionally, we compared our optimized light delivery to a commercially available light delivery system, and conclude that our optimized geometry could improve imaging depth more than 1.6×, bringing the imaging depth to within the needed range for transabdominal imaging of the human placenta.

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