Evidence for a shift in placental HLA-G allelic dominance and the HLA-G isoform profile during a healthy pregnancy and pre-eclampsia

2021 ◽  
Author(s):  
Gry Persson ◽  
Christina Seefeldt Stæhr ◽  
Freja Syrach Klok ◽  
Morten Lebech ◽  
Thomas Vauvert F Hviid
Keyword(s):  
Expression Patterns ◽  
Human Leukocyte ◽  
First Trimester ◽  
Protein Levels ◽  
Classical Class ◽  
Significant Difference ◽  
Allele Expression ◽  
Placental Blood ◽  
Insertion Allele ◽  
G 14

Abstract Human leukocyte antigen (HLA)-G is a non-classical class Ib major expressed by placental trophoblast cells plays a central role in establishing tolerance to the semi-allogeneic fetus and in placentation. HLA-G exists in different soluble or membrane-bound isoforms. Pre-eclampsia, a major cause of fetal and maternal morbidity and mortality, has been linked to insufficient placentation and an altered immune response in pregnancy, including altered HLA-G expression. The 14 bp insertion/deletion polymorphism in the 3′ untranslated region of the gene and the isoform profile may affect HLA-G expression. The aim of the current pilot study was to characterize the expression patterns of HLAG mRNA, protein and isoform profile in uncomplicated term pregnancies and in cases of pre-eclampsia. Maternal sHLA-G mRNA and protein levels was slightly reduced in pre-eclampsia. No difference was found for placental blood, and no correlation between peripheral and placental sHLA-G levels was found. We observed no association between neither fetal nor maternal HLA-G 14 bp insertion/deletion genotypes and pre-eclampsia, nor a significant difference in isoform profiles. However, in HLA-G 14 bp insertion/deletion heterozygous placental samples, we observed abundant HLA-G1 14 bp insertion allele expression in the term placentae, which is contrary to previous findings in first trimester trophoblast. Increased HLA-G1 14 bp insertion allele expression in the placenta was associated with reduced levels of placental sHLA-G and an altered isoform profile with increased relative levels of HLA-G1 and -G5 and reduced levels of HLA-G3. The results indicate that an allelic shift in heterozygous individuals could represent a novel regulatory pathway.

207. The expression of caspase-14 in the human placenta

2005 ◽  
Vol 17 (9) ◽  
pp. 79
Author(s):  
A. Charles ◽  
S. Hisheh ◽  
D. W. R. Kam ◽  
A. M. Dharmarajan
Keyword(s):  
Human Placenta ◽  
First Trimester ◽  
Explant Culture ◽  
Control Group ◽  
Term Placenta ◽  
Protein Levels ◽  
Significant Difference ◽  
Cytotrophoblast Cells ◽  
Immunohistochemical Studies

Pro-apoptotic genes have a role in the differentiation process in the placenta leading to the fusion of cytotrophoblast cells to form the protective syncytiotrophoblast layer. The mechanisms of apoptosis in the human placenta are not clearly understood. However, a major placental apoptotic-signalling pathway is known to involve the caspases. Caspase-14 is the most recently discovered member of the caspase family members and has not previously been examined in the human placenta. The aim of the present study was to detect caspase-14 in the human placenta and study its role in apoptosis. Human placentae were collected from first trimester and term gestation. The study consisted of two parts. In the first part, first trimester and term placentae were assessed for caspase-14 by western blotting and mRNA analysis and localised with immunohistochemical studies. In the second part, apoptosis in first trimester placenta was inhibited in an in-vitro model of explant villi culture with superoxide dismutase (SOD) treatment and the genes assessed. The first study demonstrated caspase-14 to be a cytoplasmic protein localised in the cytotrophoblast cells, the mesenchyme and in the syncytiotrophoblast of the first trimester. In the term placenta, caspase-14 was expressed weakly in the syncytiotrophoblast. The immunostaining data suggest a higher expression of caspase-14 in the first trimester compared to the term placenta, and this observation was later confirmed by western blot analysis. Using the SOD in-vitro explant culture model, no significant difference in the caspase-14 protein levels were seen in either the SOD or control group. This novel study demonstrates for the first time that caspase-14 protein and mRNA are present in the human placenta. The function of caspase-14 in the human placenta is unclear.

scholarly journals The relationship of HLA-G 14-bp insertion/deletion genetic polymorphism to the risk of multiple sclerosis and its clinical phenotypes

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Wafaa M. Farghaly ◽  
Heba M. Saad Eldien ◽  
Mohammed A. Sayed ◽  
Hassan M. Elnady ◽  
Ashraf Khodeary ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Polymorphism ◽  
Clinical Characteristics ◽  
Human Leukocyte ◽  
Healthy Controls ◽  
University Hospitals ◽  
Presenting Symptoms ◽  
Significant Difference ◽  
Degree Of Disability ◽  
G 14

Abstract Background Human leukocyte antigen (HLA)-G molecule has been suggested to have a potential immunomodulatory role in multiple sclerosis (MS). Genetic variant sites of HLA-G molecule have been reported to be associated with autoimmune diseases. Identifying the genetic risk factors of MS may help in preventive strategies and anticipating disease progression. The aim of this work was to investigate the effect of HLA-G 14-base-pair insertion/deletion (14-bp INS/DEL) genetic polymorphism on MS risk and clinical characteristics and to observe the clinical characteristics of the MS patients’ group. The study included 48 MS patients and 50 cross-matched healthy controls, who were recruited from Sohag and Assiut university hospitals. Genetic testing (14-bp Ins/Del gene polymorphism) using polymerase chain reaction (PCR) was performed for patients and control groups. All patients had a detailed clinical assessment and have undergone measurement of disability using the Expanded Disability Status Scale (EDSS). Results No statistically significant difference was found between MS patients and healthy controls (HC) in genotypic and allelic frequencies of HLA-G 14-bp INS/DEL polymorphism (P=0.305). No significant association was found between HLA-G 14-bp INS/DEL polymorphism genotypes and clinical characteristics or degree of disability of MS patients. The most frequent presenting symptoms of MS were motor symptoms. Fatigue was the most reported symptom along the course of MS disease. Conclusion Although it has been long known that HLA-G represents an important MS susceptibility locus, in this study, no significant relation could be detected between the 14-bp INS/DEL polymorphism genotype and MS susceptibility. MS risk susceptibility may be not linked to a single allele but may depend on the combination of different polymorphic genetic sites. In this study, the lack of genetic susceptibility may be attributed to ethnic factor.

Optimisation of tactics of conducting pregnancy and labours at women after auxiliary reproductive technologies

2016 ◽  
pp. 160-164
Author(s):  
D.N. Maslo ◽  
Keyword(s):  
Pregnant Women ◽  
Resistance Index ◽  
First Trimester ◽  
Reproductive Technologies ◽  
Premature Delivery ◽  
Control Group ◽  
Uterine Arteries ◽  
Placental Dysfunction ◽  
Placental Blood ◽  
Two Stages

The objective: frequency decrease perinatal pathologies at women after ART on the basis of studying clinical-ehografical, endocrinological, biochemical, dopplerometrical, cardiotokografical and morphological researches, and also improvement of algorithm of diagnostic and treatment-and-prophylactic actions. Patients and methods. The work basis is made spent by us from 2012 on 2015 by complex inspection of 300 pregnant women from which 250 were after ART and 50 – firstlabours which pragnency without ART, and also their newborns. For the decision of an object in view of research spent to two stages. At 1 stage spent prosperctive research which included 150 pregnant women: з them 100 women pregnancy at which has come out ART (1 group) and 50 healthy women (control group). At 2 stage spent prospective randomization in which result of patients after ART have divided on two equal groups by therapy principle: 2 basic group - 75 pregnant women after ART at which used the algorithm improved by us; 3 group of comparison - 75 pregnant women after ART which have been spent on the standard treatment-and-prophylactic actions. Results. The results suggest that women after using ART is a high frequency of reproductive losses in the first trimester (10.0%), 3.0% of spontaneous abortion from 16 to 22 weeks, and 3.0% "early" premature delivery (22 to 28 weeks of pregnancy). The frequency of violations of the functional state of placenta in women after using IVF is 63.0%, which is the main cause of high levels of perinatal losses (40.0 ‰), and delivery by cesarean section (96.0%). Placental dysfunction in women after using ART characterized by retrohorialnyh hematoma (21.0%); size mismatch fruit (30.0%) and hypertonicity of the uterus (73.0%) against changes in fruit-placental blood flow - increased resistance index in umbilical artery and increased vascular resistance in the uterine arteries. Endocrinological and biochemical changes in placental dysfunction in women after using IVF starting from 28 weeks of pregnancy and are in significant reduction in progesterone, placental b1-microglobulin, B2-microglobulin of fertility and trophic в-glycoprotein. Conclusion. The received results: use of the algorithm of diagnostic and treatment-and-prophylactic actions improved by us allows to lower frequency of spontaneous interruption of pregnancy till 22 weeks – from 13.0% to 5.7%; «early» premature birth – from 3.0% to 1.0%; placentary dysfunction from 63.0% to 40.6%; cesarean sections – from 96.0% to 56.5%, and also perinatal losses – from 40.0‰ to 16.2‰. Key words: pregnancy, childbirth, auxiliary reproductive technologies.

scholarly journals Like wings of a bird: functional divergence and complementarity between HLA-A and HLA-B molecules

2020 ◽  
Author(s):  
Da Di ◽  
Jose Manuel Nunes ◽  
Wei Jiang ◽  
Alicia Sanchez-Mazas
Keyword(s):  
Balancing Selection ◽  
Functional Divergence ◽  
Peptide Binding ◽  
Human Leukocyte ◽  
Environmental Pressures ◽  
Protein Levels ◽  
Functional Complementarity ◽  
Vital Functions ◽  
Almost All ◽  
Immune Potential

Abstract Human leukocyte antigen (HLA) genes are among the most polymorphic of our genome, as a likely consequence of balancing selection related to their central role in adaptive immunity. HLA-A and HLA-B genes were recently suggested to evolve through a model of joint divergent asymmetric selection conferring all populations, including those with severe loss of diversity, an equivalent immune potential. However, the mechanisms by which these two genes might undergo joint evolution while displaying very distinct allelic profiles in populations worldwide are still unknown. To address this issue, we carried out extensive data analyses (among which factorial correspondence and linear modelling) on 2,909 common and rare HLA-A, HLA-B and HLA-C alleles and 200,000 simulated pathogenic peptides by taking into account sequence variation, predicted peptide-binding affinity and HLA allele frequencies in 123 populations worldwide. Our results show that HLA-A and HLA-B (but not HLA-C) molecules maintain considerable functional divergence in almost all populations, which likely plays an instrumental role in their immune defence. We also provide robust evidence of functional complementarity between HLA-A and HLA-B molecules, which display asymmetric relationships in terms of amino acid diversity at both inter- and intra-protein levels and in terms of promiscuous or fastidious peptide-binding specificities. Like two wings of a flying bird, the functional complementarity of HLA-A and HLA-B is a perfect example, in our genome, of duplicated genes sharing their capacity of assuming common vital functions while being submitted to complex and sometimes distinct environmental pressures.

scholarly journals Transformation and functional verification of Cry5Aa in cotton

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shihao Zhao ◽  
Feng Wang ◽  
Qiuping Zhang ◽  
Jiayi Zou ◽  
Zhangshu Xie ◽  
...  
Keyword(s):  
Resistance Gene ◽  
Insect Resistance ◽  
Expression Patterns ◽  
Instar Larva ◽  
Cotton Bollworm ◽  
Pcr Analysis ◽  
Functional Verification ◽  
Study Results ◽  
Significant Difference ◽  
Transgenic Strains

AbstractMost of the cotton bollworm-resistant genes applied in cotton are more than 20 years and they all belong to Cry1Ab/c family, but the insect-resistant effects of Cry5Aa on cotton were rarely reported. The possible risk of resistance is increasing. The study synthesized a novel bollworm-resistant gene Cry5Aa artificially based on preferences of cotton codon. The new gene was transferred to cotton through the method of pollen tube pathway. The transgenic strains were identified by kanamycin test in field and laboratory PCR analysis. Meanwhile, an insect resistance test was conducted by artificial bollworm feeding with transgenic leaves and GK19 was used as a control in this study. Results showed that rate of positive transgenic strains with kanamycin resistance in the first generation (T1), the second generation (T2) and the third generation (T3) respectively were 7.76%, 73.1% and 95.5%. However, PCR analysis showed that the positive strain rate in T1, T2 and T3 were 2.35%, 55.8% and 94.5%, respectively. The resistant assay of cotton bollworm showed that the mortality rate of the second, third and fourth instar larva feed by the transgenic cotton leaves, were 85.42%, 73.35% and 62.79%, respectively. There was a significant difference between transgenic plant of Cry5Aa and GK19 in insect resistance. Finally, we also conducted the further analysis of gene expression patterns, gene flow and the effect on non-target pest in the study. The results showed that Cry5Aa gene had less environmental impact, and Cry5Aa has been transferred successfully and expressed stably in cotton. Therefore, the novel bollworm resistance gene can partially replace the current insect-resistance gene of Lepidoptera insects.

Long-term treadmill training ameliorates endothelium-dependent vasorelaxation mediated by insulin and insulin-like growth factor-1 in hypertension

2015 ◽  
Vol 119 (6) ◽  
pp. 663-669 ◽  
Author(s):  
Yi-Yuan Lin ◽  
Shin-Da Lee ◽  
Chia-Ting Su ◽  
Tsung-Lin Cheng ◽  
Ai-Lun Yang
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Treadmill Training ◽  
Control Group ◽  
Insulin Like Growth Factor ◽  
Hypertensive Rats ◽  
Protein Levels ◽  
Significant Difference ◽  
Nos Inhibitors

Dysfunction of insulin and insulin-like growth factor-1 (IGF-1) is associated with the pathophysiology of hypertension. The influence of long-term exercise on vascular dysfunction caused by hypertension remains unclear. We investigated whether long-term treadmill training improved insulin- and IGF-1-mediated vasorelaxation in hypertensive rats. Eight-week-old male spontaneously hypertensive rats (SHR) were randomly divided into sedentary and exercise (SHR-EX) groups. The SHR-EX group was trained on a treadmill for 60 min/day, 5 days/wk, for 8 wk. Wistar-Kyoto rats (WKY) were used as the normal control group. After training, aortic insulin- and IGF-1-mediated vasorelaxation was evaluated in organ baths. Additionally, the roles of phosphatidylinositol 3-kinase (PI3K), nitric oxide synthase (NOS), and aortic protein expression were examined in the three groups. Compared with sedentary SHR and WKY groups, insulin- and IGF-1-mediated vasorelaxation was significantly enhanced to a nearly normal level in the SHR-EX group. After endothelial denudation, blunted and comparable vasorelaxation was found among the three groups. Pretreatment with selective PI3K and NOS inhibitors attenuated insulin- and IGF-1-mediated vasorelaxation, and no significant difference was found among the three groups after the pretreatment. The aortic protein levels of the insulin receptor (IR), IGF-1 receptor (IGF-1R), insulin receptor substrate-1 (IRS-1), and endothelial NOS (eNOS) were also significantly increased in the SHR-EX group compared with the other two groups. These results suggested that treadmill training elicited the amelioration of endothelium-dependent insulin/IGF-1-mediated vasorelaxation partly via the increased activation of PI3K and NOS, as well as the enhancement of protein levels of IR, IGF-1R, IRS-1, and eNOS, in hypertension.

scholarly journals Birdsong Decreases Protein Levels of FoxP2, a Molecule Required for Human Speech

2008 ◽  
Vol 100 (4) ◽  
pp. 2015-2025 ◽  
Author(s):  
Julie E. Miller ◽  
Elizabeth Spiteri ◽  
Michael C. Condro ◽  
Ryan T. Dosumu-Johnson ◽  
Daniel H. Geschwind ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Target Genes ◽  
Expression Patterns ◽  
Vocal Learning ◽  
Brain Regions ◽  
Motor Deficits ◽  
Mrna Levels ◽  
Adult Males ◽  
Protein Levels ◽  
Area X

Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia, and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Because FoxP2 is a transcription factor, a role in shaping circuits likely depends on FoxP2 protein levels which might not always parallel mRNA levels. Indeed our current study shows that FoxP2 protein, like its mRNA, is acutely downregulated in mature Area X when adult males sing with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability.

Genome-wide screening of m6A-modified transcript in the Wilms’ tumor

2021 ◽  
Author(s):  
Zhuo Liu ◽  
Feng He ◽  
Jing Liu ◽  
Shengrong OuYang ◽  
Zexi Li ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Real Time ◽  
Real Time Pcr ◽  
Wilms Tumor ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Gene Ontology Analysis ◽  
Quantitative Real Time Pcr ◽  
Related Factors ◽  
Significant Difference

Abstract Background Wilms’ tumor, also called nephroblastoma, is the most common pediatric renal malignancy. The pathogenesis of Wilms’ tumor has been attributed to several genetic and epigenetic factors. However, the most pervasive internal mRNA modification that affects almost every process of RNA metabolism, RNA N6-Methyladenosine (m6A) methylation, has not been characterized in Wilms’ tumor. Methods Wilms’ tumor (WT) and adjacent non-cancerous (NC) tissue samples were obtained from 23 children with nephroblastoma, and the global m6A levels were measured by mass spectrometry. Analyses by m6A-mRNA epitranscriptomic microarray and mRNA microarray were performed, and m6A-related mRNAs were validated by quantitative real-time PCR for input and m6A-immunoprecipitated RNA samples from WT and NC tissues. Gene ontology analysis and KEGG pathway analysis were performed for differentially expressed genes, and expression of RNA methylation-related factors was measured by quantitative real-time PCR. Results The total m6A methylation levels in total RNA of WT samples and NC samples were (0.21 ± 0.01)% and (0.22 ± 0.01)%, respectively, with no statistically significant difference. Fifty-nine transcripts were differentially m6A-methylated between the WT and NC groups, which showed distinct m6A modification patterns. Gene ontology analysis indicated that m6A-modified genes were enriched in cancer-associated pathways, including the mTOR pathway, and conjoint analysis of the unique methylation and gene expression patterns in WT samples suggested an association with metabolic pathways.The mRNA levels of the m6A-related “reader” genes, YTHDF1, YTHDF2 and IGF2BP3, were statistically higher in WT samples than in NC samples. Conclusion This is the first study to determine the m6A modification profiles in Wilms’ tumor. Our data provide novel information regarding patterns of m6A modification that correlate with carcinogenesis in Wilms’ tumor.

The role of the platelet profile in the prediction of gestational diabetes

2021 ◽  
pp. 50-54
Keyword(s):  
Body Mass Index ◽  
Blood Glucose ◽  
Gestational Diabetes ◽  
Pregnant Women ◽  
Body Mass ◽  
First Trimester ◽  
Oral Glucose ◽  
Mean Corpuscular Hemoglobin ◽  
Lymphocyte Ratio ◽  
Significant Difference

Objective: In our study, the results of oral glucose tolerance test (OGTT) and other hemogram parameters of pregnant women with and without gestational diabetes mellitus (GDM) were compared. The aim of our study is to investigate the benefit of these parameters in predicting GDM risk. Material and Method: The study was planned as a descriptive, retrospective and cross-sectional study. It was included 218 pregnant women who applied to the Gynecology and Obstetrics Clinic of Amasya Sabuncuoğlu Şerefeddin Training and Research Hospital between January 01, 2019 and January 31, 2020. It was examined complete blood count parameters, ultrasound findings, complete urinalysis, first trimester blood glucose, body mass index, age, and gravide parameters the patients we included in the study. The results were analyzed retrospectively and was evaluated the statistical significance relationship with gestational diabetes. Results: There was no statistically significant difference in age, body mass index (BMI), obesity status and number of gravida between the pregnant women who were examined and those without GDM (p> 0.05). The hemoglobin, platelet count, mean platelet volume (MPV), mean corpuscular volume (MCV), mean corpuscular hemoglobine (MCH), and mean corpuscular hemoglobin concentration (MCHC) values, and neutrophil, lymphocyte, monocyte and basophil counts, urine density and femur length were statistically significant. There was no difference (p> 0.05). No statistically significant difference was found in terms of neutrophile lymphocyte ratio (NLR), neutrophile monocyte ratio (NMR), platelet lymphocyte ratio (PLR), monocyte eosinophil ratio (MER), platelet MPV ratio (PMPVR), and platelet neutrophile ratio (PNR) values (p> 0.05) Conclusion: HbA1c, hematocrit and blood glucose in the first trimester may be predictors of GDM. In addition, we think that further studies are needed in a prospective design in more patients in terms of others parameters.

scholarly journals Establishment of peritoneal liquid electrophoretogram from healthy horses and horses submitted to experimentally induced intestinal obstruction

2014 ◽  
Vol 66 (3) ◽  
pp. 665-671 ◽  
Author(s):  
A.F.S. Nogueira ◽  
P.A. Di Filippo ◽  
L.A. Anai ◽  
M.C. Vieira ◽  
K.M.M.G. Simplício ◽  
...  
Keyword(s):  
Intestinal Obstruction ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Immunoglobulin A ◽  
Control Group ◽  
Protein Levels ◽  
Sds Page ◽  
Significant Difference ◽  
Page Electrophoresis ◽  
Experimentally Induced

The initial inflammatory stages of the colic syndrome include changes known as acute phase response. The aim of this study was to contribute with the establishment of reference values concerning the electrophoretogram of peritoneal liquid from healthy horses and horses submitted to experimentally induced intestinal obstruction. Twenty-one horses were allotted in four groups: duodenal obstruction (DG), ileum obstruction (IG), left-dorsal colon obstruction (MG), and control group (CG). Peritoneal liquid was sampled before obtruction (T0), with 3 hours of obstruction (T3) and 6, 30, 102 and 174 hours after desobstructing (T6, T30, T102 and T174, respectively). Total protein levels were determined by the biuret method and protein fractions were obtained by SDS-PAGE electrophoresis. The acute phase proteins (APP) identified were Immunoglobulin-A, ceruloplasmin, transferrin, albumin, α1-antitrypsin, heavy and light chains of immunoglobulin-G, haptoglobin, α1-acid glycoprotein and a still unnamed protein, which was called P24. There was no difference (P>0.3) in protein levels among groups, although a significant difference (P>0.05) was observed between distinct experimental moments in each group evidencing a higher response of the APP in the obstructed groups. The APP fractioning of the peritoneal liquid was standardized to establish a standard curve for healthy equines and those submitted to induced intestinal obstruction. Moreover, it was verified that the SDS-PAGE electrophoresis was sensitive and effective to help diagnose abdominal inflammatory processes.

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