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

2021 ◽  
Vol 89 (1) ◽  
pp. 27-36
Author(s):  
Iván Acevedo Monterrosa ◽  
Damián A. Soria ◽  
Analía Tomat ◽  
Rosana Elesgaray ◽  
Cristina Arranz ◽  
...  

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.

2019 ◽  
Vol 2 (1) ◽  
pp. 77-82
Author(s):  
Abha Shrestha ◽  
N Pradhan ◽  
B Kayastha

Background: Intrauterine growth restricted (IUGR) fetuses are at higher risk of developing neonatal complications and also known to develop metabolic syndrome in adult life. So, an early antenatal detection, choosing the optimal time and method of delivery and intervention when required could minimize the risk significantly. Objective: To find out the prenatal outcome and the maternal and placental risk factors. Methods: A prospective study was conducted from January 2010 to January 2019, at a Teaching Hospital. A singleton pregnancy, above 28 weeks of gestation with clinical diagnosis of IUGR and confirmed by ultrasonography were included in the study. The statistical analysis was performed by Statistical Package of Social Sciences (SPSS) 23.0 software. Results: Maternal risk factors like low pregnancy body mass index, preeclampsia, anaemia, hypothyroidism and placental factors like retro placental hemorrhage were mainly responsible for intrauterine growth restriction. Conclusions: The early identification of risk factors and management of the same antenatal is an important issue to prevent adverse prenatal outcomes associated with IUGR.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A741-A742
Author(s):  
Domingo Mugnolo ◽  
Erica Giraldo ◽  
Maria Perez Lana ◽  
Susana Beatriz Campeni

Abstract Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders that affects between 5- 10% of women of reproductive age. It is currently considered a complex and multifactorial disease with metabolic, cardiovascular implications and represents per se an increased cancer risk. PATIENTS with PCOS routinely have menstrual disorders, hyperandrogenism, infertility and reproductive complications such as recurrent abortions, gestational diabetes, intrauterine growth restriction, pregnancy induced hypertension that give rise to underweight newborns and condition metabolic diseases to adult life and increased risk of cancer, especially breast and endometrial cancer. Insulin resistance and hyperandrogenism are the most important etiopathogenic factors in PCOS. On the other hand, subjects exposed to an adverse microenvironment in the intrauterine stage develop compensating responses to survive, a process called fetal programming. Prenatal exposure to androgens and/or insulin resistance may act as fetal programming factors and cause restriction of intrauterine growth, obesity and insulin resistance in offspring. Newborn may have an increased risk of metabolic syndrome, increased incidence of hypertensive, type 2 diabetes, heart disease and cerebrovascular disease. Prevention of these complications will be achieved if women with Polycystic Ovary Syndrome are treated appropriately throughout their lives, but especially before and during their pregnancy. Only in this way can the risk of them be reduced, representing a better quality and greater life expectancy.


BMJ Open ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. e020501
Author(s):  
Edurne Mazarico ◽  
Anna Peguero ◽  
Marta Camprubí ◽  
Carlota Rovira ◽  
Maria Dolores Gomez Roig ◽  
...  

IntroductionThe incidence of intrauterine growth restriction (IUGR) is estimated at about 3% of pregnancies, and it is associated with 30% of all perinatal mortality and severe morbidity with adverse neurodevelopmental and cardiovascular health consequences in adult life. Early onset IUGR represents 20%–30% of all cases and is highly associated with severe placental insufficiency. The existing evidence suggests that low molecular weight heparin (LMWH) has effects beyond its antithrombotic action, improving placental microvessel structure and function of pregnant women with vascular obstetric complications by normalising proangiogenic and antiapoptotic protein levels, cytokines and inflammatory factors. The objective of our study is to demonstrate the effectiveness of LMWH in prolonging gestation in pregnancies with early-onset IUGR.Methods and analysisThis is a multicentre, triple-blind, parallel-arm randomised clinical trial. Singleton pregnancies qualifying for early (20–32 weeks at diagnosis) placental IUGR (according to Delphi criteria) will be randomised to subcutaneous treatment with bemiparin 3500 IU/0.2 mL/day or placebo from inclusion at diagnosis to the time of delivery. Analyses will be based on originally assigned groups (intention-to-treat). The primary objective will be analysed by comparing gestational age and prolongation of pregnancy (days) in each group with Student’s t-tests for independent samples and by comparing Kaplan-Maier survival curves (from inclusion to delivery, log-rank test). A linear regression model for gestational age at birth will consider the following covariates: gestational age at inclusion (continuous) and pre-eclampsia (binary).Ethics and disseminationThe study will be conducted in accordance with the principles of Good Clinical Practice. This study was approved by the Clinical Research Ethics Committee (CEIC) of Sant Joan de Déu Hospital, on 13 July 2017. The trial is registered in the public registrywww.clinicaltrial.gov. according to Science Law 14/2011, and the results will be published in an open access journal.Trial registration numberNCT03324139; Pre-results.


2020 ◽  
Vol 78 (1) ◽  
Author(s):  
Desalegn Tesfa ◽  
Melaku Tadege ◽  
Alemayehu Digssie ◽  
Sofonyas Abebaw

Abstract Background After prematurity, intrauterine growth restriction (IUGR) is the second leading cause of perinatal mortality. IUGR has significant consequences in fetal, neonatal, and adult life. Currently, Ethiopia lacks information on IUGR’s prevalence and its determinants. This study aimed to assess the proportion of IUGR at birth and its associated factors. Methods A cross-sectional study was carried out among women who give birth in four hospitals of south Gonder zone from November 2018 to February 2019. Multi-stage sampling was applied to select the required samples. IUGR was assessed using a standardized cutoff percentile/mean for each measurement. Data were collected by trained MSc clinical midwives. Bi-variable and multivariable logistic analyses were deployed to identify the association. Results A total of 803 maternity women were participating in this study with a response rate of 95%. The proportion of IUGR 23.5% (95% CI: 20.7–26.6), low birth weight 13.3%, small-for- gestational-age 19.7%,and preterm birth 23.16%. Women who was unable to read and write, (AOR; 2.46, 95% CI: 1.02–5.92), total family size ≥7 (AOR; 1.67, 95% CI: 1.04–2.66), maternal mid-upper arm circumference (MUAC) < 23 cm (AOR; 2.10, 95% CI: 1.39–3.01), body mass index (BMI) < 18.5 kg/m2 (AOR; 2.57, 95% CI: 1.72–3.83), altitude > 3000 m (AOR; 1.89 95% CI: 1.19–3.01), small placental size (< 350 g) (AOR; 2.42, 95% CI: 1.67–3.54) and small-for-gestational-age (AOR; 1.94, 95% CI:1.86–4.52) were the most predictors of IUGR. Conclusions IUGR was a major public health concern in this study. Women who were unable to read and write, small-for-gestational-age, maternal BMI < 18.5 kg/m2, family size ≥7, maternal MUAC < 23 cm, small placental size, and altitude > 3000 m were found the most predictor variables. Strengthen female education, nutritional intervention before and during pregnancy, and routine maternity care is critical. Further clinical follow-up research is essential which includes maternal, fetal, and placental gens.


2018 ◽  
Vol 50 (5) ◽  
pp. 1764-1778 ◽  
Author(s):  
Linyuan Shen ◽  
Shunhua Zhang ◽  
Qiang Li ◽  
Yuhua Fu ◽  
Guoqing Tang ◽  
...  

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.


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