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Influences of Maternal Stress during Pregnancy on the Epi/genome: Comparison of Placenta and Umbilical Cord Blood.

ABSTRACT: Background:Maternal stress during pregnancy is one of the major adverse environmental factors in utero that is capable of influencing health outcomes of the offspring throughout life. Both genetic and epigenetic processes are susceptible to environmental insults in utero and are potential biomarkers of the experienced environment including maternal stress. Methods:We profiled expression level of six genes in hypothalamic pituitary adrenal (HPA) axis functioning (HSD11B2, SLC6A4, NR3C1, NR3C2, CRHR1 and CRHR2), two imprinted genes (IGF2 and H19) and one neurodevelopmental gene (EGR1), from 49 pairs of placenta and umbilical cord blood (UCB) samples from a birth cohort. We also assessed global methylation levels by LUminometric Methylation Assay (LUMA) and methylation at the imprinting control region (ICR) of IGF2/H19. Results:Little correlations between paired placenta and UCB were observed except H19 expression (r = 0.31, P = 0.04) and IGF2/H19 ICR methylation (r = 0.43, P = 0.01); gene expression levels were significantly higher (P < 0.001) in placenta than UCB except CRHR1 and CRHR2, which were unexpressed in placenta. Maternal stress correlated higher levels of HPA genes and lower levels of EGR1 and LUMA, but only in placenta. Positive association between maternal stress and IGF2/H19 ICR methylation was present in both placenta and UCB. Conclusions:Our findings support the notion that adverse in utero environment, as measured by antenatal maternal stress, depression and anxiety, can be observed in the epi/genome of the relevant tissues, i.e. placenta and UCBs, leading to development of molecular markers for assessing in utero adversities.

SUBMITTER: Chen J

PROVIDER: S-EPMC6020835 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Influences of Maternal Stress during Pregnancy on the Epi/genome: Comparison of Placenta and Umbilical Cord Blood.

Chen Jia J Li Qian Q Rialdi Alexender A Mystal Elana E Ly Jenny J Finik Jackie J Davey Taira T Lambertini Luca L Nomura Yoko Y

Journal of depression & anxiety 20140225 2

<h4>Background</h4>Maternal stress during pregnancy is one of the major adverse environmental factors in utero that is capable of influencing health outcomes of the offspring throughout life. Both genetic and epigenetic processes are susceptible to environmental insults in utero and are potential biomarkers of the experienced environment including maternal stress.<h4>Methods</h4>We profiled expression level of six genes in hypothalamic pituitary adrenal (HPA) axis functioning (HSD11B2, SLC6A4, N ...[more]

PMID: 29963333

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Project description:ObjectiveNo validated biomarker at birth exists to predict which newborns will develop severe hyperbilirubinemia. This study's primary aim was to build and validate a prediction model for severe hyperbilirubinemia using umbilical cord blood bilirubins (CBB) and risk factors at birth in neonates at risk for maternal-fetal blood group incompatibility. This study's secondary aim was to compare the accuracy of CBB to the direct antigen titer.MethodsInclusion criteria for this prospective cohort study included: ≥35 weeks gestational age, mother with blood type O and/or Rh negative or positive antibody screen, and <24 hours of age. The primary outcome was severe hyperbilirubinemia, defined as phototherapy during the initial hospital stay. Secondary outcomes were a total serum bilirubin concentration >95th and >75th percentile during the initial hospital stay. The predictive performance and accuracy of the two tests (CBB and direct antigen titer) for each outcome was assessed using area under a receiver-operating characteristic curve (AUC), sensitivity, and specificity.ResultsWhen compared to neonates who did not receive phototherapy (n = 463), neonates who received phototherapy (n = 36) had a greater mean CBB ± standard deviation (2.5 ± 0.7 vs. 1.6 ± 0.4 mg/dL, p<0.001). For every 0.3 mg/dL increase in CBB, a neonate was 3.20 (95% confidence interval, 2.31-4.45), 2.10 (1.63-2.70), and 3.12 (2.44-3.99) times more likely to receive phototherapy or have a total serum bilirubin concentration >95th and >75th percentile, respectively. The AUC ± standard error (95% confidence interval) for CBB for phototherapy and a total serum bilirubin concentration >95th and >75th percentile was 0.89 ± 0.03 (0.82-0.95), 0.81 ± 0.04 (0.73-0.90), and 0.84 ± 0.02 (0.80-0.89), respectively. However, the AUC for gestational age and maternal Asian race for these outcomes was only 0.55 ± 0.05 (0.45-0.66), 0.66 ± 0.05 (0.56-0.76), and 0.57 ± 0.04 (0.05-0.64), respectively. When the CBB was combined with gestational age and maternal Asian race, the AUC for a total serum bilirubin concentration >95th percentile improved to 0.87 ± 0.03 (0.81-0.92) (p = 0.034 vs. the model with CBB only and p<0.001 vs. the model with clinical risk factors only). In a sub-group of subjects (n = 189), the AUC for the direct antigen titer for phototherapy was 0.64 ± 0.06 (0.52-0.77) with a 52% sensitivity and 77% specificity. In contrast, a CBB cut-point of 1.85 mg/dL was 92% sensitive and 70% specific for phototherapy with an AUC of 0.87 ± 0.04 (0.80-0.95).ConclusionCBB, in combination with gestational age and maternal race, may be a useful, non-invasive test to predict shortly after birth which neonates will develop severe hyperbilirubinemia.

Project description:BackgroundUmbilical cord blood could serve as useful source of blood markers enabling more efficient and reliable prenatal and neonatal diagnostics. MicroRNAs (miRNAs) are ubiquitous in body fluids where they were used for detecting and monitoring various physiological and pathological conditions. In this descriptive study, we aimed to identify changes in miRNA expression profiles associated with basic maternal somatic and epidemiological characteristics.MethodsStudy is based on 24 mothers from the Pilot phase of CELSPAC: TNG (Central European Longitudinal Studies of Parents and Children: The Next Generation) study. Cord blood was collected at time of delivery and global miRNA profiling was performed using microRNA Ready-to-use PCR Human Panel I+II TaqMan microarrays. Expression profiles were statistically evaluated in relation to maternal age, BMI, pregnancy weight gain, blood type, Rh factor status, allergies during pregnancy, addictive substance abuse and smoking status.ResultsWe analyzed expression of 752 human mature miRNAs in 24 samples of umbilical cord blood. For all maternal characteristics tested we described a specific signature of significantly deregulated miRNAs (P < 0.05). Analysis revealed seven miRNA associated with maternal age (three increased and four decreased in women younger than 35 years), 14 miRNAs associated with BMI status (five miRNAs increased and nine miRNAs decreased in women with BMI > 25) and nine miRNAs associated with maternal weight gain during pregnancy (eight miRNAs increased, and one miRNA decreased in women with weight gain < 12 kg). Additionally, 17 miRNAs correlated to blood type (two miRNAs decreased in blood type A, 11 increased in blood type B, two miRNAs increased in blood type AB and two miRNAs increased in blood type 0) and 17 miRNAs to Rh status of mother. We also detected seven miRNAs deregulated in umbilical cord blood of women with allergy (four increased and three decreased in women with allergy), four miRNAs associated to addictive substance abuse status (two up- and two downregulated in women with addictive substance abuse) and eight miRNAs associated with maternal cigarette smoking during pregnancy.ConclusionsWe successfully described differences in miRNA profiles in umbilical cord blood associated with basic characteristics connected with mother. Our data suggest that miRNAs in umbilical cord blood are detectable and associated with a wide range of maternal characteristics. These results indicate that miRNAs could potentially serve, and should be studied, as biomarkers for screening and diagnosis of pregnancy-associated complications and pathologies.

Project description:Although recent studies have demonstrated that microRNAs (miRNAs or miRs) regulate fundamental natural killer (NK) cellular processes, including cytotoxicity and cytokine production, little is known about the miRNA-gene regulatory relationships in maternal peripheral blood NK (pNK) cells during pregnancy. In the present study, to determine the roles of miRNAs within gene regulatory networks of maternal pNK cells, we performed comprehensive miRNA and gene expression profiling of maternal pNK cells using a combination of reverse transcription quantitative PCR (RT-qPCR)-based miRNA array and DNA microarray analyses and analyzed the differential expression levels between first- and third-trimester pNK cells. Furthermore, we constructed regulatory networks for miRNA-mediated gene expression in pNK cells during pregnancy by Ingenuity Pathway Analysis (IPA). PCR-based array analysis revealed that the placenta-derived miRNAs [chromosome 19 miRNA cluster (C19MC) miRNAs] were detected in pNK cells during pregnancy. Twenty-five miRNAs, including six C19MC miRNAs, were significantly upregulated in the third- compared to first-trimester pNK cells. The rapid clearance of C19MC miRNAs also occurred in the pNK cells following delivery. Nine miRNAs, including eight C19MC miRNAs, were significantly downregulated in the post-delivery pNK cells compared to those of the third-trimester. DNA microarray analysis identified 69 NK cell function-related genes that were differentially expressed between the first- and third-trimester pNK cells. On pathway and network analysis, the observed gene expression changes of pNK cells likely contribute to the increase in the cytotoxicity, as well as the cell cycle progression of third- compared to first-trimester pNK cells. Thirteen of the 69 NK cell function-related genes were significantly downregulated between the first- and third-trimester pNK cells. Nine of the 13 downregulated NK-function-associated genes were in silico target candidates of 12 upregulated miRNAs, including C19MC miRNA miR-512-3p. The results of this study suggest that the transfer of placental C19MC miRNAs into maternal pNK cells occurs during pregnancy. The present study provides new insight into maternal NK cell functions.

Dataset Information

Influences of Maternal Stress during Pregnancy on the Epi/genome: Comparison of Placenta and Umbilical Cord Blood.

Publications

Influences of Maternal Stress during Pregnancy on the Epi/genome: Comparison of Placenta and Umbilical Cord Blood.

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