scholarly journals Chronic hypoxia during development does not trigger pathologic remodeling of the chicken embryonic heart but reduces cardiomyocyte number

2015 ◽  
Vol 309 (10) ◽  
pp. R1204-R1214 ◽  
Author(s):  
Hanna Österman ◽  
Isa Lindgren ◽  
Tom Lindström ◽  
Jordi Altimiras
Keyword(s):  
Chronic Hypoxia ◽  
Ventricular Remodeling ◽  
Strong Support ◽  
Growth Restriction ◽  
Cardiac Insufficiency ◽  
Early Maturation ◽  
Rat Pups ◽  
Increased Risk ◽  
Cardiomyocyte Number ◽  
Hypoxic Incubation

Fetal growth restriction programs an increased risk of cardiovascular disease in adulthood, but the actual mechanisms of this developmental programming are not fully understood. Previous studies in mammalian models suggest that hearts of growth-restricted fetuses have reduced cardiomyocyte number due to reduced proliferation and premature cardiomyocyte maturation. Chicken embryos incubated under chronic hypoxia are also growth-restricted, have smaller hearts, and show signs of cardiac insufficiency posthatching. The aim of the present study was to investigate how chronic hypoxia (14% O2) during development affects cardiomyocyte mass and how myocardial structure is altered. Hypoxic incubation reproduced the well-characterized embryonic growth restriction and an increased ventricle-to-body mass ratio (at E11, E15, E17, and E19) with reduced absolute heart mass only at E19. Cell density, apoptosis, and cardiomyocyte size were insensitive to hypoxia at E15 and E19, and no signs of ventricular wall remodeling or myocardial fibrosis were detected. Bayesian modeling provided strong support for hypoxia affecting absolute mass and proliferation rates at E15, indicating that the growth impairment, at least partly, occurs earlier in development. Neither E15 nor E19 hearts contained binucleated cardiomyocytes, indicating that fetal hypoxia does not trigger early maturation of cardiomyocytes in the chicken, which contrasts with previous results from hypoxic rat pups. In conclusion, prenatal hypoxia in the chick embryo results in a reduction in the number of cardiomyocytes without inducing ventricular remodeling, cell hypertrophy, or premature cardiomyocyte maturation.

Pathological features of the sequence in pregnant women with delayed fetal growth

2019 ◽  
pp. 50-54
Author(s):  
V.O. Golyanovskiy ◽  
◽  
Ye.O. Didyk ◽  
Keyword(s):  
Pregnant Women ◽  
Intrauterine Growth Restriction ◽  
Normal Development ◽  
Intrauterine Infection ◽  
Normal Pregnancy ◽  
Growth Restriction ◽  
Control Group ◽  
Intrauterine Growth ◽  
Increased Risk ◽  
Infection And Inflammation

Pregnant women with intrauterine growth restriction (IUGR) have an increased risk of adverse perinatal and long-term complications compared with the birth of children with normal body weight. Thus, IUGR is one of the main challenges for the global health system, especially in poor and developing countries. Morpho-functional studies of the placentas help in determining the causes of IUGR, and therefore, timely prevent complications in pregnant women with IUGR. The objective: The purpose of this study is to investigate various morphometric and pathomorphological changes in the placenta, including inflammatory, in cases of IUGR, and to establish a correlation of these results with the etiology and complications for the fetus. Materials and methods. In the current study, 54 placentas of the fetuses with IUGR (the main group) were compared with 50 placentas of the fetuses with normal development (control group). The criteria for the inclusion of IUGR were gestational age more than 30 weeks and all fetuses with a weight less than 10th percentile for this period of pregnancy. The placenta material was studied pathomorphologically with laboratory screening for infection and inflammation. Similarly, the results were determined for placentas of the fetuses with normal development compared to placentas with IUGR. Results. The placenta study showed the presence of calcification in the case of IUGR, as well as in the case of prolonged pregnancy. However, calcification of the placenta in the case of IUGR was more progressive compared with placenta in the normal pregnancy. In addition, the presence of intrauterine infection and inflammation was observed, which could also lead to an adverse outcome for the further progression of pregnancy with IUGR. Conclusion. A comparative macro- and microscopic pathomorphological study of the placentas in the two groups has shown a significant increase in the pathological changes in all the anatomical structures of the fetuses with IUGR. Key words: Intrauterine growth restriction (IUGR), fetal weight, pathomorphological changes of the placenta.

scholarly journals Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thiago Ferreira de Souza ◽  
Thiago Quinaglia Silva ◽  
Lígia Antunes-Correa ◽  
Zsofia D. Drobni ◽  
Felipe Osório Costa ◽  
...  
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Right Ventricular ◽  
Ventricular Remodeling ◽  
Interstitial Fibrosis ◽  
Systolic Dysfunction ◽  
Extracellular Volume ◽  
Increased Risk ◽  
Tissue Characteristics ◽  
A Prospective Study

AbstractThere are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310–517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P < 0.001). RV mass-index and RV CM decreased to 13 ± 2.8 g/m2 and 8.13 ± 2 g/m2, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (P < 0.001). The RV ECV expansion correlated with a decrease in RV mass-index (r = −0.46; P < 0.001) and the increase in CK-MB. An RV ESV index at baseline above its median predicted an increased risk of LV dysfunction post-anthracyclines. In BC patients treated with anthracyclines, RV atrophy, systolic dysfunction, and a parallel increase of diffuse interstitial fibrosis indicate a cardiotoxic response on a similar scale as previously seen in the systemic left ventricle.

Epigenetic mechanisms involved in intrauterine growth restriction and aberrant kidney development and function

2020 ◽  
pp. 1-11
Author(s):  
Thu N. A. Doan ◽  
Jessica F. Briffa ◽  
Aaron L. Phillips ◽  
Shalem Y. Leemaqz ◽  
Rachel A. Burton ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Intrauterine Growth Restriction ◽  
Kidney Development ◽  
Dna Methyltransferases ◽  
Growth Restriction ◽  
Epigenetic Mechanisms ◽  
Specific Expression ◽  
Maternal Line ◽  
Intrauterine Growth ◽  
Increased Risk

Abstract Intrauterine growth restriction (IUGR) due to uteroplacental insufficiency results in a placenta that is unable to provide adequate nutrients and oxygen to the fetus. These growth-restricted babies have an increased risk of hypertension and chronic kidney disease later in life. In rats, both male and female growth-restricted offspring have nephron deficits but only males develop kidney dysfunction and high blood pressure. In addition, there is transgenerational transmission of nephron deficits and hypertension risk. Therefore, epigenetic mechanisms may explain the sex-specific programming and multigenerational transmission of IUGR-related phenotypes. Expression of DNA methyltransferases (Dnmt1and Dnmt3a) and imprinted genes (Peg3, Snrpn, Kcnq1, and Cdkn1c) were investigated in kidney tissues of sham and IUGR rats in F1 (embryonic day 20 (E20) and postnatal day 1 (PN1)) and F2 (6 and 12 months of age, paternal and maternal lines) generations (n = 6–13/group). In comparison to sham offspring, F1 IUGR rats had a 19% decrease in Dnmt3a expression at E20 (P < 0.05), with decreased Cdkn1c (19%, P < 0.05) and increased Kcnq1 (1.6-fold, P < 0.01) at PN1. There was a sex-specific difference in Cdkn1c and Snrpn expression at E20, with 29% and 34% higher expression in IUGR males compared to females, respectively (P < 0.05). Peg3 sex-specific expression was lost in the F2 IUGR offspring, only in the maternal line. These findings suggest that epigenetic mechanisms may be altered in renal embryonic and/or fetal development in growth-restricted offspring, which could alter kidney function, predisposing these offspring to kidney disease later in life.

Hepatic IGF1 DNA methylation is influenced by gender but not by intrauterine growth restriction in the young lamb

2015 ◽  
Vol 6 (6) ◽  
pp. 558-572 ◽  
Author(s):  
D. J. Carr ◽  
J. S. Milne ◽  
R. P. Aitken ◽  
C. L. Adam ◽  
J. M. Wallace
Keyword(s):  
Dna Methylation ◽  
Growth Hormone ◽  
Sexual Dimorphism ◽  
Mrna Expression ◽  
Intrauterine Growth Restriction ◽  
Messenger Rna ◽  
Methylation Status ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Increased Risk

Intrauterine growth restriction (IUGR) and postnatal catch-up growth confer an increased risk of adult-onset disease. Overnourishment of adolescent ewes generates IUGR in ∼50% of lambs, which subsequently exhibit increased fractional growth rates. We investigated putative epigenetic changes underlying this early postnatal phenotype by quantifying gene-specific methylation at cytosine:guanine (CpG) dinucleotides. Hepatic DNA/RNA was extracted from IUGR [eight male (M)/nine female (F)] and normal birth weight (12 M/9 F) lambs. Polymerase chain reaction was performed using primers targeting CpG islands in 10 genes: insulin, growth hormone, insulin-like growth factor (IGF)1, IGF2, H19, insulin receptor, growth hormone receptor, IGF receptors 1 and 2, and the glucocorticoid receptor. Using pyrosequencing, methylation status was determined by quantifying cytosine:thymine ratios at 57 CpG sites. Messenger RNA (mRNA) expression of IGF system genes and plasma IGF1/insulin were determined. DNA methylation was independent of IUGR status but sexual dimorphism in IGF1 methylation was evident (M<F, P=0.008). IGF1 mRNA:18S and plasma IGF1 were M>F (both P<0.001). IGF1 mRNA expression correlated negatively with IGF1 methylation (r=−0.507, P=0.002) and positively with plasma IGF1 (r=0.884, P<0.001). Carcass and empty body weights were greater in males (P=0.002–0.014) and this gender difference in early body conformation was mirrored by sexual dimorphism in hepatic IGF1 DNA methylation, mRNA expression and plasma IGF1 concentrations.

scholarly journals Intrauterine Growth Restriction and the Fetal Programming of the Hedonic Response to Sweet Taste in Newborn Infants

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Caroline Ayres ◽  
Marilyn Agranonik ◽  
André Krumel Portella ◽  
Françoise Filion ◽  
Celeste C. Johnston ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Fetal Programming ◽  
Intrauterine Growth Restriction ◽  
Sucrose Solution ◽  
Sweet Taste ◽  
Growth Restriction ◽  
Fetal Life ◽  
Intrauterine Growth ◽  
Sweet Solution ◽  
Increased Risk

Intrauterine growth restriction is associated with increased risk for adult metabolic syndrome and cardiovascular disease, which seems to be related to altered food preferences in these individuals later in life. In this study, we sought to understand whether intrauterine growth leads to fetal programming of the hedonic responses to sweet. Sixteen 1-day-old preterm infants received 24% sucrose solution or water and the taste reactivity was filmed and analyzed. Spearman correlation demonstrated a positive correlation between fetal growth and the hedonic response to the sweet solution in the first 15 seconds after the offer (r=0.864,P=0.001), without correlation when the solution given is water (r=0.314,P=0.455). In fact, the more intense the intrauterine growth restriction, the lower the frequency of the hedonic response observed. IUGR is strongly correlated with the hedonic response to a sweet solution in the first day of life in preterm infants. This is the first evidence in humans to demonstrate that the hedonic response to sweet taste is programmed very early during the fetal life by the degree of intrauterine growth. The altered hedonic response at birth and subsequent differential food preference may contribute to the increased risk of obesity and related disorders in adulthood in intrauterine growth-restricted individuals.

scholarly journals Placental Dysfunction Underlies Increased Risk of Fetal Growth Restriction and Stillbirth in Advanced Maternal Age Women

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Samantha C. Lean ◽  
Alexander E. P. Heazell ◽  
Mark R. Dilworth ◽  
Tracey A. Mills ◽  
Rebecca L. Jones
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Maternal Age ◽  
Advanced Maternal Age ◽  
Growth Restriction ◽  
Placental Dysfunction ◽  
Increased Risk

Somatic growth and the risks of bronchopulmonary dysplasia and pulmonary hypertension: connecting epidemiology and physiology

2019 ◽  
Vol 97 (3) ◽  
pp. 197-205 ◽  
Author(s):  
Mark A. Underwood ◽  
Stephen Wedgwood ◽  
Satyan Lakshminrusimha ◽  
Robin H. Steinhorn
Keyword(s):  
Pulmonary Hypertension ◽  
Bronchopulmonary Dysplasia ◽  
Somatic Growth ◽  
Postnatal Growth ◽  
Pulmonary Complications ◽  
Growth Restriction ◽  
Extreme Prematurity ◽  
Poor Growth ◽  
Increased Risk ◽  
Poor Nutrition

In the premature infant, poor growth in utero (fetal growth restriction) and in the first weeks of life (postnatal growth restriction) are associated with increased risk for bronchopulmonary dysplasia and pulmonary hypertension. In this review, we summarize the epidemiologic data supporting these associations, present a novel rodent model of postnatal growth restriction, and review 5 promising mechanisms by which poor nutrition may affect the developing lung. These observations support the hypothesis that nutritional and (or) pharmacologic interventions early in life may be able to decrease risk of the pulmonary complications of extreme prematurity.

scholarly journals Cytotoxic CD8+ T Cells Promote Granzyme B-Dependent Adverse Post-Ischemic Cardiac Remodeling

2020 ◽  
Author(s):  
Icia Santos Zas ◽  
Jeremie Lemarie ◽  
Ivana Zlatanova ◽  
Marine Cachanado ◽  
Jean-Christophe Seghezzi ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Ventricular Remodeling ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Granzyme B ◽  
Acute Ischemia ◽  
Risk Of Death ◽  
Increased Risk ◽  
Acute Mi

Abstract Acute myocardial infarction (MI) is a common condition responsible for heart failure and sudden death. Here, we show that following acute MI in mice, CD8+ T lymphocytes are recruited and activated in the ischemic heart tissue, and release Granzyme B leading to cardiomyocyte apoptosis, adverse ventricular remodeling and deterioration of myocardial function. Depletion of CD8+ T lymphocytes decreases apoptosis within the ischemic myocardium, hampers inflammatory response, limits myocardial injury and improves heart function. These effects are recapitulated in mice with Granzyme B-deficient CD8+ T cells. The protective effect of CD8 depletion on heart function was confirmed by using a model of ischemia/reperfusion in pigs. Finally, we reveal that elevated circulating levels of Granzyme B in patients with acute MI predict increased risk of death at 1-year follow-up. Our work unravels an unsuspected deleterious role of CD8+ T lymphocytes following acute ischemia, and identifies novel therapeutic strategy targeting pathogenic CD8+ T lymphocytes in the setting of acute MI.

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