The Landscape of Non-Coding RNA in an Adult Pig Model of Intrauterine Growth Restriction

Background/Aims: Intrauterine growth restriction (IUGR) is a risk factor for adult metabolic syndrome, but how this disease is regulated by lncRNAs and circRNAs remains elusive. Methods: Here, we employed adult IUGR and normal pigs as models to evaluate the expression of various global lncRNAs and circRNAs in pig livers using RNA-seq. Results: In total, we obtained 1,162 million raw reads of approximately 104.54 Gb high quality data. After a strict five-step filtering process, 3,368 lncRNAs were identified, including 300 differentially expressed lncRNAs (p < 0.05) in the IUGR group relative to the control group. The cis-regulatory analysis identified target genes that were enriched in specific GO terms and pathways (p < 0.05), including amino acid metabolism, oxidoreductase activity, PPAR signaling pathway, and insulin signaling pathway. These are closely related to the observed phenotypes of increased gluconeogenesis and impaired mitochondrial oxidative phosphorylation in adulthood of the IUGR group. Additionally, we also identified 403 circRNAs, of which 44 were differentially expressed (p < 0.05). Interestingly, our results identified ATF4-miR214-circRNA7964 and TCF7-miR22-3p-circRNA16347 as two competing endogenous networks, which were closely associated with the observed increase in hepatic gluconeogenesis in the IUGR group. Conclusion: Together, this study reveals a multitude of candidate lncRNAs and circRNAs involved in the development of IUGR pigs, which could facilitate further researches on the molecular mechanisms of metabolic syndrome.

Download Full-text

Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174415007242 ◽

2015 ◽

Vol 7 (1) ◽

pp. 91-101 ◽

Cited By ~ 5

Author(s):

L. Chen ◽

J. Yue ◽

X. Han ◽

J. Li ◽

Y. Hu

Keyword(s):

Calcium Signaling ◽

Signaling Pathway ◽

Pathway Analysis ◽

Intrauterine Growth Restriction ◽

Kegg Pathway ◽

Growth Restriction ◽

Differentially Expressed ◽

Intrauterine Growth ◽

Kegg Pathway Analysis ◽

Calcium Signaling Pathway

Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.

Download Full-text

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

HEALTH OF WOMAN ◽

10.15574/hw.2019.140.50 ◽

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.

Download Full-text

Is ProBNP a New Marker for Predicting Intrauterine Growth Restriction?

Zeitschrift für Geburtshilfe und Neonatologie ◽

10.1055/a-1382-8787 ◽

2021 ◽

Vol 225 (02) ◽

pp. 125-128

Author(s):

Hasan Eroğlu ◽

Nazan Vanlı Tonyalı ◽

Gokcen Orgul ◽

Derya Biriken ◽

Aykan Yucel ◽

...

Keyword(s):

Intrauterine Growth Restriction ◽

Final Analysis ◽

First Trimester ◽

Maternal Serum ◽

Growth Restriction ◽

Control Group ◽

Aneuploidy Screening ◽

Intrauterine Growth ◽

Potential Marker ◽

The Mean

Abstract Purpose To evaluate the usability of first-trimester maternal serum ProBNP levels in the prediction of intrauterine growth restriction (IUGR). Methods In this prospective study, blood samples taken from 500 women who applied to our polyclinic for routine serum aneuploidy screening between the 11–14th gestational weeks were centrifuged. The obtained plasma samples were placed in Eppendorf tubes and stored at −80+°C. For the final analysis, first-trimester maternal serum ProBNP levels of 32 women diagnosed with postpartum IUGR and 32 healthy women randomly selected as the control group were compared. FGR was defined as estimated fetal weight below the 10th percentile for the gestational age. Results The mean ProBNP levels were statistically and significantly higher in the women with intrauterine growth restriction (113.73±94.69 vs. 58.33±47.70 pg/mL, p<0.01). At a cut-off level of 50.93, ProBNP accurately predicted occurrence of IUGR (AUC+= 0.794 (95% confidence interval 0.679–0.910), p+= 0.001) with sensitivity and specificity rates of 78.1 and 69.0%, respectively. Conclusion First-trimester serum ProBNP level was significantly higher in women who developed IUGR compared to healthy controls. First-trimester ProBNP level can be used as a potential marker to predict the development of IUGR in pregnant women.

Download Full-text

Association of maternal and/or fetal factor V Leiden and G20210A prothrombin mutation with HELLP syndrome and intrauterine growth restriction

Clinical Science ◽

10.1042/cs20030073 ◽

2003 ◽

Vol 105 (3) ◽

pp. 279-285 ◽

Cited By ~ 31

Author(s):

Dietmar SCHLEMBACH ◽

Ernst BEINDER ◽

Juergen ZINGSEM ◽

Ute WUNSIEDLER ◽

Matthias W. BECKMANN ◽

...

Keyword(s):

Blood Flow ◽

Intrauterine Growth Restriction ◽

Hellp Syndrome ◽

Factor V Leiden ◽

Growth Restriction ◽

Control Group ◽

Factor V ◽

Intrauterine Growth ◽

Prothrombin Mutation ◽

Thrombophilic Mutations

This study was conducted to investigate the association of maternal and/or fetal factor V Leiden (FVL) and G20210A prothrombin mutation with HELLP syndrome. FVL and G20210A prothrombin mutation were determined using PCR. Sixty-three pregnant women, 36 of them diagnosed with HELLP syndrome, were included in the study. Overall, 68 children were born as a result of these pregnancies and blood sampling was possible in 28 out of 39 children from HELLP patients and 25 out of 29 children from the control women. The prevalence of a maternal FVL was elevated 2-fold in HELLP patients compared with the control women [six out of 36 (16.7%) compared with two out of 27 (7.4%); P=0.282]. None of the HELLP patients and only one woman in the control group was found to be positive for the G20210A prothrombin mutation (P=0.251). The fetal carrier frequency was four out of 28 compared with three out of 25 for FVL (P=0.811), and two out of 28 compared with one out of 25 for G20210A prothrombin mutation (P=0.629). Intrauterine growth restriction (IUGR) was significantly higher in fetuses found to be positive for a thrombophilic mutation (P=0.022). IUGR occurred in seven out of ten fetuses with a thrombophilic mutation compared with 11 out of 43 in fetuses without a mutation. The prevalence of FVL, but not of the G20210A prothrombin mutation, seems to be elevated in women with HELLP syndrome. A fetal thrombophilic mutation does not contribute significantly to the clinical features of the HELLP syndrome. Our results demonstrate a fetal contribution to IUGR. Fetal thrombophilic mutations may lead to placental microthrombosis, which consecutively could lead to a disturbed fetoplacental blood flow and thus cause growth restriction.

Download Full-text

Intrauterine Programming of Adult Disease: Identification of Cardinal Genes Associated with Hypertension, Obesity and Metabolic Syndrome

10.7775/rac.v89.i1.19666 ◽

2021 ◽

Vol 89 (1) ◽

pp. 27-36

Author(s):

Iván Acevedo Monterrosa ◽

Damián A. Soria ◽

Analía Tomat ◽

Rosana Elesgaray ◽

Cristina Arranz ◽

...

Keyword(s):

Metabolic Syndrome ◽

Intrauterine Growth Restriction ◽

Adult Life ◽

Treatment Strategies ◽

Interaction Network ◽

Growth Restriction ◽

Adult Disease ◽

Intrauterine Growth ◽

Significant Gene ◽

Obesity Hypertension

Background: Intrauterine growth restriction is an abnormal fetal development characterized by a fetal growth rate lower than the potential genetic growth for the gestational age. This condition represents a major burden for public health systems, as it increases short and long-term morbidity and mortality in the offspring, particularly because of its association with the development of cardiovascular and metabolic disease in adult life. Objectives: The aim of the present study was to identify possible cardinal genes involved in intrauterine growth restriction associated with the development of obesity, hypertension and metabolic syndrome using bioinformatics tools. Methods: A total of 343 genes involved in the phenotypes of interest were obtained and 20 genes were identified as significantly relevant in the interaction network analysis. Specifically, four of these identified genes encode for growth factors or their receptors, VEGFA, PDGFRB, IGF1R and EGFR. We also identified genes related to insulin and cardiovascular homeostasis as CTNNB1, APP, MYC and MDMD2. Cluster analysis provided the most significant gene ontology terms, including those related to the biological processes of proliferation and programmed cell death, intercellular communication, protein metabolism and development of the cardiovascular system. Conclusions: The genes found in this study could be useful as putative biomarkers for the presence of cardiovascular and metabolic disorders associated with intrauterine growth restriction, or as potential therapeutic targets for treatment strategies directed to the patient's genotype.

Download Full-text

Mean Platelet Volume is Affected in Term Fetuses with Intrauterine Growth Restriction

Zeitschrift für Geburtshilfe und Neonatologie ◽

10.1055/a-1177-1773 ◽

2020 ◽

Author(s):

Gul Nihal Buyuk ◽

Z.Asli Oskovi-Kaplan ◽

Aysegul Oksuzoglu ◽

H.Levent Keskin

Keyword(s):

High Risk ◽

Pregnant Women ◽

Mean Platelet Volume ◽

Intrauterine Growth Restriction ◽

Growth Restriction ◽

Control Group ◽

Platelet Volume ◽

Intrauterine Growth ◽

Potential Marker ◽

The Mean

Abstract Objectives The aim of our study was to analyze the mean platelet volume levels as a potential marker of altered placentation in intrauterine growth restriction (IUGR) cases. Methods A total of 126 term singleton pregnant women with IUGR fetuses and 345 healthy pregnant controls were recruited and compared. Results The mean platelet volume was significantly higher in the IUGR group (10.8±0.9 fl) than the control group (9.9±1.1 fl) (p=0.03). The mean hemoglobin was lower in IUGR group (11.3 (8.3–14.5) g/dl) than the control group (11.9 (8.2–13.0) g/dl) (p=0.04). The optimal cut-off MPV for prediction of IUGR was ≥10.55 fl, with a sensitivity of 59% and a specificity of 75%. Conclusion Increased MPV levels in term pregnant women may be particularly helpful for discrimination and prediction of high-risk fetuses when IUGR is suspected.

Download Full-text

N-Carbamylglutamate and l-Arginine Promote Intestinal Absorption of Amino Acids by Regulating the mTOR Signaling Pathway and Amino Acid and Peptide Transporters in Suckling Lambs with Intrauterine Growth Restriction

Journal of Nutrition ◽

10.1093/jn/nxz016 ◽

2019 ◽

Vol 149 (6) ◽

pp. 923-932 ◽

Cited By ~ 3

Author(s):

Hao Zhang ◽

Along Peng ◽

Yin Yu ◽

Shuang Guo ◽

Mengzhi Wang ◽

...

Keyword(s):

Amino Acid ◽

Signaling Pathway ◽

Intrauterine Growth Restriction ◽

Nutrient Absorption ◽

Mtor Signaling ◽

Growth Restriction ◽

Peptide Transporter ◽

Mtor Signaling Pathway ◽

Intrauterine Growth ◽

Peptide Transporters

ABSTRACT Background Previous studies have revealed that dietary N-carbamylglutamate (NCG) and l-arginine (Arg) improve intestinal integrity, oxidative state, and immune function in Hu suckling lambs with intrauterine growth restriction (IUGR). Whether these treatments alter intestinal nutrient absorption is unknown. Objective The aim of this study was to determine the influence of dietary NCG and Arg treatment during the suckling period on intestinal amino acid (AA) absorption, alterations in the mechanistic target of rapamycin (mTOR) signaling pathway, and the abundance of AA and peptide transporters in IUGR lambs. Methods On day 7 after birth, 48 newborn Hu lambs were selected from a cohort of 424 twin lambs. Normal-birth-weight and IUGR Hu lambs were allocated randomly (n = 12/group) to a control (4.09 ± 0.12 kg), IUGR (3.52 ± 0.09 kg), IUGR + 0.1% NCG (3.49 ± 0.11 kg), or IUGR + 1% Arg (3.53 ± 0.10 kg). Results At day 28, compared with the IUGR group, the IUGR groups receiving NCG and Arg had 7.4% and 7.2% greater (P < 0.05) body weight, respectively. Compared with the IUGR group, the serum concentration of insulin was greater (P < 0.05) and the cortisol was lower (P < 0.05) in the IUGR groups receiving NCG and Arg. Compared with the IUGR group, the IUGR groups receiving NCG and Arg had 13.2%–62.6% greater (P < 0.05) serum concentrations of arginine, cysteine, isoleucine, and proline. Dietary NCG or Arg to IUGR lambs resulted in greater protein abundance (P < 0.05) of peptide transporter 1 (41.9% or 38.2%) in the ileum compared with the unsupplemented IUGR lambs, respectively. Furthermore, dietary NCG or Arg treatment normalized the IUGR-induced variation (P < 0.05) in the ileal ratio of phosphorylated mTOR to total mTOR protein. Conclusion Both NCG and Arg can help mitigate the negative effect of IUGR on nutrient absorption in neonatal lambs.

Download Full-text

Parental factors associated with intrauterine growth restriction

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1512701h ◽

2015 ◽

Vol 143 (11-12) ◽

pp. 701-706 ◽

Cited By ~ 3

Author(s):

Monica Hăşmăşanu ◽

Sorana Bolboacă ◽

Tudor Drugan ◽

Melinda Matyas ◽

Gabriela Zaharie

Keyword(s):

Risk Factors ◽

Intrauterine Growth Restriction ◽

Newborn Infants ◽

Significant Risk ◽

Growth Restriction ◽

University Hospital ◽

Control Group ◽

Parental Factors ◽

Intrauterine Growth ◽

Significant Difference

Introduction. Linear growth failure is caused by multiple factors including parental factors. Objective. The aim of this study was to evaluate parental risk factors for intrauterine growth restriction (IUGR) on a population of Romanian newborn infants in a tertiary level maternity facility for a period of 2.5 years. Methods. A retrospective matched case-control study was conducted in the Emergency County Hospital of Cluj-Napoca, a university hospital in North-Western Romania. The sample was selected from 4,790 infants admitted to the Neonatal Ward at 1st Gynecology Clinic between January 2012 and June 2014. Results. The age of mothers was significantly lower in the IUGR group compared to controls (p=0.041). A significantly higher percentage of mothers had hypertension in the IUGR group compared to those in the control group (p<0.05). No other significant differences were identified with regard to the investigated characteristics of mothers between IUGR infants compared to controls (p>0.13). The age of fathers of infants with IUGR proved significantly lower compared to controls (p=0.0278). The analysis of infants? comorbidities revealed no significant difference between groups for respiratory distress, hyperbilirubinemia, hypocalcaemia, and heart failure (p>0.27). Intracranial hemorrhage, necrotizing enterocolitis and hypoglycemia were significantly higher in the IUGR group compared to controls. The logistic regression identified hypertension as a significant risk factor for IUGR (OR=2.4, 95% CI [1.3-4.5]). Conclusion. Although the age of the mothers and fathers proved significantly lower in the IUGR group compared to controls, only hypertension in the mothers proved significant risk factors for IUGR.

Download Full-text

Cardiac left heart morphology and function in newborns with intrauterine growth restriction: relevance for long-term assessment

Medical Ultrasonography ◽

10.11152/mu-1667 ◽

2019 ◽

Vol 21 (1) ◽

pp. 62

Author(s):

Gabriela Corina Zaharie ◽

Monica Hasmasanu ◽

Ligia Blaga ◽

Melinda Matyas ◽

Daniel Muresan ◽

...

Keyword(s):

Intrauterine Growth Restriction ◽

Systolic Dysfunction ◽

Left Ventricular ◽

Growth Restriction ◽

Control Group ◽

Left Heart ◽

Functional Changes ◽

Intrauterine Growth ◽

Cardiac Adaptation ◽

And Function

Aim: To asses the cardiac morphology and functional changes specific for newborns from intrauterine growth restriction (IUGR) pregnancies.Material and method: A cohort of IUGR infants were evaluated by serial echocardiographies at delivery and at the first and six months follow-ups. IUGR newborn delivery status was compared to that of newborns in the control group according to gestational age (AGA).Results: Left heart measurements were significantly lower in IUGR newborns compared to AGA babies. Left ventricular size increased at follow-up inthe IUGR group (p<0.05). Systolic dysfunction (the myocardial performance index (MPI)> 0.47) was identified in 40% of the neonates in the IUGR group (16/40), respectively 4.76% in the control group. IUGR neonates had a significantly increased proportion of systolic malfunction (p=0.004).Conclusion: IUGR patients had reduced left ventricle dimensions compared to AGA babies. The MPI stands out as a marker of leftheart function in newborns. Systolic dysfunction was a hallmark of the cardiac adaptation in IUGR neonates.

Download Full-text

The predictive value of fetal middle cerebral artery/descending aorta ratio doppler parameter in the evaluation of perinatal results of intrauterine growth restriction

European Journal of Clinical and Experimental Medicine ◽

10.15584/ejcem.2020.4.2 ◽

2021 ◽

Vol 18 (4) ◽

pp. 268-274

Author(s):

Gokmen Sukgen ◽

◽

Omer Kaya ◽

Keyword(s):

Middle Cerebral Artery ◽

Cerebral Artery ◽

Intrauterine Growth Restriction ◽

Perinatal Outcomes ◽

Growth Restriction ◽

Control Group ◽

Predictive Values ◽

Descending Aorta ◽

Intrauterine Growth ◽

Doppler Parameter

Introduction. Although there are various reasons for intrauterine growth restriction (IUGR), the main cause is inadequate utero- placental and feto-placental circulation. Aim. To determine the predictive values of fetal middle cerebral artery/descending aorta (MCA/DA) Doppler parameter in the evaluation of perinatal outcomes in pregnancies with IUGR. Material and methods. 15 with IUGR and 35 normal newborn, who were born at the 34th gestational week or over included into the study. Doppler ultrasonography (US) measurements were performed. The ratio of pulsatility index/resistive index (PI/ RI) from MCA, umbilical artery (Umb), DA was determined. Neonatal characteristics such as Apgar scores, neonatal intensive care unit (NICU) requirement, weight and sex were also recorded. Results. In the IUGR group, mean MCA/DA RI-PI, MCA/UmB RI-PI were 0.88±0.19, 0.86±0.28, 1.22±0.18 and 1.55±0.39, respectively. In the control group, mean MCA/DA RI-PI, MCA/UmB RI-PI were 1.15±0.13, 1.09±0.41, 1.37±0.35 and 1.82±0.44, respectively. There were statistically significant relationship between MCA/DA PI with cord blood pH value and NICU requirement, age with gravida, parity, MCA/UmB RI, MCA/UmB PI; gravida with age and parity; parity with age, gravida, weight, MCA/DA RI, PI ratios. Conclusion. Intrauterine MCA and DA Doppler US parameters of IUGR can be used safely in predicting perinatal outcomes in pregnancies with IUGR over 34 weeks.

Download Full-text