Intrauterine growth restriction promotes vascular remodelling following carotid artery ligation in rats

2012 ◽  
Vol 123 (7) ◽  
pp. 437-444 ◽  
Author(s):  
Carlos Menendez-Castro ◽  
Nada Cordasic ◽  
Matthias Schmid ◽  
Fabian Fahlbusch ◽  
Wolfgang Rascher ◽  
...  

Epidemiological studies revealed an association between IUGR (intrauterine growth restriction) and an increased risk of developing CVDs (cardiovascular diseases), such as atherosclerosis or hypertension, in later life. Whether or not IUGR contributes to the development of atherosclerotic lesions, however, is unclear. We tested the hypothesis that IUGR aggravates experimentally induced vascular remodelling. IUGR was induced in rats by maternal protein restriction during pregnancy (8% protein diet). To detect possible differences in the development of vascular injury, a model of carotid artery ligation to induce vascular remodelling was applied in 8-week-old intrauterine-growth-restricted and control rat offspring. Histological and immunohistochemical analyses were performed in the ligated and non-ligated carotid arteries 8 weeks after ligation. IUGR alone neither caused overt histological changes nor significant dedifferentiation of VSMCs (vascular smooth muscle cells). After carotid artery ligation, however, neointima formation, media thickness and media/lumen ratio were significantly increased in rats after IUGR compared with controls. Moreover, dedifferentiation of VSMCs and collagen deposition in the media were more prominent in ligated carotids from rats after IUGR compared with ligated carotids from control rats. We conclude that IUGR aggravates atherosclerotic vascular remodelling induced by a second injury later in life.

2019 ◽  
pp. 50-54
Author(s):  
V.O. Golyanovskiy ◽  
◽  
Ye.O. Didyk ◽  

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.


Author(s):  
Thu N. A. Doan ◽  
Jessica F. Briffa ◽  
Aaron L. Phillips ◽  
Shalem Y. Leemaqz ◽  
Rachel A. Burton ◽  
...  

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.


2015 ◽  
Vol 6 (6) ◽  
pp. 558-572 ◽  
Author(s):  
D. J. Carr ◽  
J. S. Milne ◽  
R. P. Aitken ◽  
C. L. Adam ◽  
J. M. Wallace

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.


2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Caroline Ayres ◽  
Marilyn Agranonik ◽  
André Krumel Portella ◽  
Françoise Filion ◽  
Celeste C. Johnston ◽  
...  

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.


2017 ◽  
Vol 8 (5) ◽  
pp. 604-612 ◽  
Author(s):  
S. Perzel ◽  
H. Huebner ◽  
W. Rascher ◽  
C. Menendez-Castro ◽  
A. Hartner ◽  
...  

Intrauterine growth restriction (IUGR) and fetal growth restriction (FGR) are pregnancy complications associated with morbidity in later life. Despite a growing body of evidence from current research on developmental origins of health and disease (DOHaD), little information is currently provided to parents on long-term metabolic, cardiovascular and neurologic consequences. As parents strongly rely on internet-based health-related information, we examined the quality of information on IUGR/FGR sequelae and DOHaD in webpages used by laypersons. Simulating non-clinicians experience, we entered the terms ‘IUGR consequences’ and ‘FGR consequences’ into Google and Yahoo search engines. The quality of the top search-hits was analyzed with regard to the certification through the Health On the Net Foundation (HON), currentness of cited references, while reliability of information and DOHaD-related consequences were assessed via the DISCERN Plus score (DPS). Overall the citation status was not up-to-date and only a few websites were HON-certified. The results of our analysis showed a dichotomy between the growing body of evidence regarding IUGR/FGR-related sequelae and lack of current guidelines, leaving parents without clear directions. Furthermore, detailed information on the concept of DOHaD is not provided. These findings emphasize the responsibility of the individual physician for providing advice on IUGR/FGR-related sequelae, monitoring and follow-up.


2019 ◽  
Vol 10 (6) ◽  
pp. 627-635 ◽  
Author(s):  
Y. Nozawa ◽  
M. D. H. Hawlader ◽  
F. Ferdous ◽  
R. Raqib ◽  
F. Tofail ◽  
...  

AbstractNumerous studies have investigated the risk of developing asthma due to early-life experiences and environmental exposures. However, the influence of intrauterine growth restriction and postnatal undernutrition on childhood wheezing/asthma remains unclear. Thus, we examined the effects of both small for gestational age (SGA) and postnatal stunted growth on ever asthma among children in the rural areas in Bangladesh.Multiple follow-up studies were conducted in a cohort of randomized clinical trial of nutrition interventions during pregnancy (the MINIMat trial). Overall, 1208 and 1697 children were followed-up for asthma at 4.5 and 10 years, respectively. Anthropometric measurements were obtained at various intervals from birth to 10 years of age. Ever asthma was identified using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire.Results showed that SGA was significantly associated with increased risk of ever asthma at 4.5 and 10 years after adjusting for sex, body mass index, socioeconomic status, family history of asthma, gestational age at birth, mother’s parity, mother’s age at birth and intervention trial arm [odds ratio (OR)=1.97 (95% confidence interval (CI): 1.34–2.90) and 1.86 (95% CI: 1.18–2.72)]. For the postnatal effect of undernutrition, stunting at 1 and 2 years was significantly associated with ever asthma at 4.5 and 10 years [1 year: OR=1.77 (95% CI: 1.22–2.57) and OR=1.72 (95% CI: 1.16–2.56), 2 years: OR=1.49 (95% CI: 1.06–2.10) and OR=1.41 (95% CI: 1.02–1.96)].In conclusion, SGA and undernutrition during infancy has an influence on childhood asthma among children in Bangladesh, indicating the need for nutritional interventions early in life.


2020 ◽  
Author(s):  
Ashley S. Brown ◽  
Matthew Wieben ◽  
Shelby Murdock ◽  
Jill Chang ◽  
Maria Dizon ◽  
...  

AbstractBackgroundChildren born with intrauterine growth restriction (IUGR) are at increased risk for cognitive impairment including learning and memory deficits. Dentate gyrus (DG) granule neurons relay cortical information into the hippocampus proper for memory formation, and their production is highly dependent on environmental signals. However, it is unknown whether IUGR affects DG neurogenesis, and thus provides a potential mechanism underlying abnormal learning and memory function.MethodsUsing a hypertensive disease of pregnancy mouse model of IUGR, we assessed multiple behaviors, quantified neural stem and progenitor cells (NSPCs) and developing neurons in the DG, and characterized transcriptional effects on molecular pathways in the hippocampus.ResultsWe found that the predominant behavioral phenotype in IUGR offspring, short-term implicit learning and memory deficits, was associated with accelerated DG neurogenesis and NSPC depletion. Consistent with known molecular regulators of DG neurogenesis, we also found strong evidence for decreased Wnt pathway activity following IUGR.ConclusionWe have discovered that postnatal memory deficits are associated with accelerated NSPC differentiation following IUGR, a phenotype that could be explained by decreased Wnt signaling.


2018 ◽  
Vol 40 (4) ◽  
pp. 344-357 ◽  
Author(s):  
Jill L. Chang ◽  
Mirrah Bashir ◽  
Christiana Santiago ◽  
Kathryn Farrow ◽  
Camille Fung ◽  
...  

Intrauterine growth restriction (IUGR) is estimated to occur in 5% of pregnancies, with placental insufficiency being the most common cause in developed countries. While it is known that white matter injury occurs in premature infants, the extent of IUGR on white matter injury is less defined in term infants. We used a novel murine model that utilizes a thromboxane A2 (TXA2) analog (U46619), a potent vasoconstrictor, to induce maternal hypertension and mimic human placental insufficiency-induced IUGR to study the white matter. We also investigated the role of hyperoxia as an additional risk factor for white matter injury, as IUGR infants are at increased risk of respiratory comorbidities leading to increased oxygen exposure. We found that TXA2 analog-induced IUGR results in white matter injury as demonstrated by altered myelin structure and changes in the oligodendroglial cell/oligodendrocyte population. In addition, our study demonstrates that hyperoxia exposure independently results in white matter perturbation. To our knowledge, this is the first study to report single and combined effects of IUGR with hyperoxia impacting the white matter and motor function. These results draw attention to the need for close monitoring of motor development in IUGR babies following hospital discharge as well as highlighting the importance of limiting, as clinically feasible, the degree of oxygen overexposure to potentially improve motor outcomes in this population of infants.


2015 ◽  
Vol 43 (5) ◽  
Author(s):  
Fadi G. Mirza ◽  
Samuel T. Bauer ◽  
Anne Van der Veer ◽  
Lynn L. Simpson

AbstractFetuses with gastroschisis are at increased risk of intrauterine growth restriction (IUGR). However, there is a tendency for underestimation of fetal abdominal circumference and hence fetal weight, leading to overdiagnosis of IUGR. Our objective was to evaluate the accuracy of ultrasound for the prediction of being small for gestational age (SGA) at birth in these cases.A retrospective study of prenatally diagnosed cases of gastroschisis was conducted at a tertiary center. Fetal weight was estimated using the formula of Hadlock. IUGR was defined as an estimated fetal weight ≤10th percentile for gestational age. SGA at the time of birth was defined as a birth weight ≤10th percentile for gestational age. The incidence of IUGR on last ultrasound and that of SGA at birth were calculated, and the precision of ultrasound in predicting SGA was determined.IUGR was reported on the last ultrasound prior to delivery in 9/25 cases (36%). Postnatally, 13/25 newborns (52%) were SGA. All sonographically suspected cases of IUGR based on the last ultrasound were SGA at birth. The positive predictive value of the last ultrasound in identifying SGA was 100%.At least half of the infants affected by gastroschisis were SGA at birth. Sonographic estimation of fetal weight within 1 month of birth reliably predicted SGA in infants with gastroschisis.


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