Louis J Muglia

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

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Publications (263)1328.17 Total impact


  • No preview · Article · Jan 2016 · American Journal of Obstetrics and Gynecology
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    ABSTRACT: Test the hypothesis that exposure to fine particulate matter in the air (PM 2.5 ) is associated with increased risk of preterm birth (PTB). Geo-spatial population-based cohort study using live birth records from Ohio (2007–2010) linked to average daily measures of PM 2.5 , recorded by 57 EPA network monitoring stations across the state. Geographic coordinates of the home residence for births were linked to the nearest monitoring station using ArcGIS. Association between PTB and high PM 2.5 levels (above the EPA annual standard of 15 μg/m 3 ) was estimated using GEE, with adjustment for age, race, education, parity, insurance, tobacco, birth season and year, and infant gender. An exchangeable correlation matrix for the monitor stations was used in the models. Analyses were limited to non-anomalous singleton births at 20-42weeks with no known chromosome abnormality occurring within 10 km of a monitor station. The frequency of PTB was 8.5 % in the study cohort of 224,921 singleton live births. High PM 2.5 exposure (>EPA recommended maximum) occurred frequently during the study period, with 24,662 women (11 %) having high exposure in all three trimesters. Pregnancies with high PM 2.5 exposure through pregnancy had increased PTB risk even after adjustment for coexisting risk factors, adjOR 1.19 (95 % CI 1.09–1.30). Assessed per trimester, high 3 rd trimester PM 2.5 exposure resulted in the highest PTB risk, adjOR 1.28 (95 % CI 1.20–1.37). Exposure to high levels of particulate air pollution, PM 2.5 , in pregnancy is associated with a 19 % increased risk of PTB; with greatest risk with high 3 rd trimester exposure. Although the risk increase associated with high PM 2.5 levels is modest, the potential impact on overall PTB rates is robust as all pregnant women are potentially at risk. This exposure may in part contribute to the higher preterm birth rates in Ohio compared to other states in the US, especially in urban areas.
    Full-text · Article · Jan 2016 · Environmental Health
  • Emily A. Defranco · Eric Hall · Louis J. Muglia
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    ABSTRACT: Background: Extremely preterm birth of a live newborn before the limit of viability is rare but contributes uniformly to the infant mortality rate as essentially all cases result in neonatal death. Objective: To quantify racial differences in previable birth and their contribution to infant mortality, and to estimate the relative influence of factors associated with live birth occurring before the threshold of viability. Study Design: Population-based retrospective cohort of all live births in Ohio over a 7-year period, 2006-2012. Demographic, pregnancy and delivery characteristics of previable live births at 16 0/7 - 22 6/7 weeks of gestation were compared to a referent group of live births at 37 0/7 – 42 6/7 weeks. Rates of birth at each week of gestation were compared between black and white mothers and relative risk ratios were calculated. Logistic regression estimated the relative risk of factors associated with previable birth, with adjustment for concomitant risk factors. Results: Of 1,034,552 live births in Ohio during the study period, 2607 (0.25% of all live births) occurred during the previable period 16-22 weeks. There is a significant racial disparity in the rate and relative risk of previable birth, with a 3 to 6 fold relative risk increase in black mothers at each week of previable gestational age. The incidence of previable birth for white mothers was 1.8 per 1000 and for black mothers, 6.9 per 1000. Factors most strongly associated with previable birth, presented as adjusted relative risk ratio (95% confidence interval), were maternal characteristics of black race adjusted relative risk 2.9 (95% CI 2.6-3.2), age ≥35 years 1.3 (CI 1.1-1.6), unmarried 2.1 (CI 1.8-2.3); fetal characteristics including congenital anomaly 5.4 (CI 3.4-8.1) and genetic disorder 5.1 (CI 2.5-10.1); and pregnancy characteristics including prior preterm birth 4.4 (CI 3.7-5.2) and multifetal gestation - twin 16.9 (CI 14.4-19.8) or triplet 65.4 (CI 32.9-130.2). The majority, 80%, of previable births (16-22 weeks) were spontaneous in nature, compared to 73% in early preterm births (23 - 33 weeks), 72% in late preterm births (34-36 weeks) and 65% of term births (37 - 42 weeks), p<0.001. Previable births constituted approximately 28% of total infant mortalities in white newborns, and 45% of infant mortalities in black infants in Ohio during the study period. Conclusions: There is a significant racial disparity in previable preterm births, with black mothers incurring 3 to 6 fold increased relative risk compared to white mothers, most of which are spontaneous in nature. This may explain much of the racial disparity in infant mortality, as all live born previable preterm births result in death. Focused efforts on prevention of spontaneous previable preterm birth may help to reduce the racial disparity in infant mortality.
    No preview · Article · Dec 2015 · American Journal of Obstetrics and Gynecology
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    ABSTRACT: Background: Although effects of weather changes on human health have been widely reported, there is limited information regarding effects on pregnant women in developing countries. Objective: To investigate the association between maternal exposure to ambient temperature and the risk of preterm birth (< 37 weeks of gestation) in Guangzhou, China. Methods: We used a Cox proportional hazards model to estimate associations between preterm birth and average temperature during each week of gestation, with weekly temperature modeled as a time-varying exposure during four time windows: 1-week, 4-week, late pregnancy (gestational week 20 onwards), and the entire pregnancy. Information on singleton vaginal birth between 2001 and 2011 was collected. Daily meteorological data during the same period were obtained from the Guangzhou Meteorological Bureau. Results: A total of 838,146 singleton vaginal births were included, amongst which 47,209 (5.6%) were preterm births. High mean temperatures during the previous 4 weeks, late pregnancy, and the entire pregnancy were associated with an increased risk of preterm birth. Compared with the median temperature (24.4°C), weekly exposures during the past 4 weeks to extreme cold (7.6°C, the 1st percentile) and extreme heat (31.9°C, the 99th percentile) were associated with 17.9% (95% CI: 10.2, 26.2%) and 10.0% (95% CI: 2.9, 17.6%) increased risks of preterm birth, respectively. The association between extreme heat and preterm birth was stronger for preterm births during weeks 20-31 and 32-34 than those during weeks 35-36. Conclusions: These findings might have important implications in preventing preterm birth in Guangzhou as well as other areas with similar weather conditions.
    Full-text · Article · Dec 2015 · Environmental Health Perspectives
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    ABSTRACT: Mammalian gestation and pregnancy are fast evolving processes that involve the interaction of the fetal, maternal and paternal genomes. Version 1.0 of the GEneSTATION database (http://genestation.org) integrates diverse types of omics data across mammals to advance understanding of the genetic basis of gestation and pregnancy-associated phenotypes and to accelerate the translation of discoveries from model organisms to humans. GEneSTATION is built using tools from the Generic Model Organism Database project, including the biology-aware database CHADO, new tools for rapid data integration, and algorithms that streamline synthesis and user access. GEneSTATION contains curated life history information on pregnancy and reproduction from 23 high-quality mammalian genomes. For every human gene, GEneSTATION contains diverse evolutionary (e.g. gene age, population genetic and molecular evolutionary statistics), organismal (e.g. tissue-specific gene and protein expression, differential gene expression, disease phenotype), and molecular data types (e.g. Gene Ontology Annotation, protein interactions), as well as links to many general (e.g. Entrez, PubMed) and pregnancy disease-specific (e.g. PTBgene, dbPTB) databases. By facilitating the synthesis of diverse functional and evolutionary data in pregnancy-associated tissues and phenotypes and enabling their quick, intuitive, accurate and customized meta-analysis, GEneSTATION provides a novel platform for comprehensive investigation of the function and evolution of mammalian pregnancy.
    Full-text · Article · Nov 2015 · Nucleic Acids Research
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    ABSTRACT: Background: Amniotic fluid (AF) is a proximal fluid to the fetus containing higher amounts of cell-free fetal RNA/DNA than maternal serum, thereby making it a promising source for identifying novel biomarkers that predict fetal development and organ maturation. Our aim was to compare AF transcriptomic profiles at different time points in pregnancy to demonstrate unique genetic signatures that would serve as potential biomarkers indicative of fetal maturation. Methods: We isolated AF RNA from 16 women at different time points in pregnancy: 4 from 18 to 24 weeks, 6 from 34 to 36 weeks, and 6 from 39 to 40 weeks. RNA-sequencing was performed on cell-free RNA. Gene expression and splicing analyses were performed in conjunction with cell-type and pathway predictions. Results: Sample-level analysis at different time points in pregnancy demonstrated a strong correlation with cell types found in the intrauterine environment and fetal respiratory, digestive and external barrier tissues of the fetus, using high-confidence cellular molecular markers. While some RNAs and splice variants were present throughout pregnancy, many transcripts were uniquely expressed at different time points in pregnancy and associated with distinct neonatal co-morbidities (respiratory distress and gavage feeding), indicating fetal immaturity. Conclusion: The AF transcriptome exhibits unique cell/organ-selective expression patterns at different time points in pregnancy that can potentially identify fetal organ maturity and predict neonatal morbidity. Developing novel biomarkers indicative of the maturation of multiple organ systems can improve upon our current methods of fetal maturity testing which focus solely on the lung, and will better inform obstetrical decisions regarding delivery timing.
    Full-text · Article · Oct 2015 · BMC Medical Genomics
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    ABSTRACT: Preterm birth is the single leading cause of mortality for neonates and children less than 5 years of age. Compared to other childhood diseases, such as infections, less progress in prevention of prematurity has been made. In large part, the continued high burden of prematurity results from the limited understanding of the mechanisms controlling normal birth timing in humans, and how individual genetic variation and environmental exposures disrupt these mechanisms to cause preterm birth. In this review, we summarize the outcomes and limitations from studies in model organisms for birth timing in humans, the evidence that genetic factors contribute to birth timing and risk for preterm birth, and recent genetic and genomic studies in women and infants that implicate specific genes and pathways. We conclude with discussing areas of potential high impact in understanding human parturition and preterm birth in the future.
    No preview · Article · Oct 2015 · Seminars in perinatology

  • No preview · Article · Sep 2015 · The Journal of pediatrics
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    ABSTRACT: Hypoplastic left heart syndrome (HLHS) is a severe cardiovascular malformation (CVM) associated with fetal growth abnormalities. Genetic and environmental factors have been identified that contribute to pathogenesis, but the role of the placenta is unknown. The purpose of this study was to systematically examine the placenta in HLHS with and without growth abnormalities. HLHS term singleton births were identified from a larger cohort when placenta tissue was available. Clinical data were collected from maternal and neonatal medical records, including anthropometrics and placental pathology reports. Placental tissues from cases and controls were analyzed to assess parenchymal morphology, vascular architecture and leptin signaling. HLHS cases (n = 16) and gestational age-matched controls (n = 18) were analyzed. Among cases, the average birth weight was 2993 g, including 31% that were small for gestational age. When compared with controls, gross pathology of HLHS cases demonstrated significantly reduced placental weight and increased fibrin deposition, while micropathology showed increased syncytial nuclear aggregates, decreased terminal villi, reduced vasculature and increased leptin expression in syncytiotrophoblast and endothelial cells. Placentas from pregnancies complicated by fetal HLHS are characterized by abnormal parenchymal morphology, suggesting immature structure may be due to vascular abnormalities. Increased leptin expression may indicate an attempt to compensate for these vascular abnormalities. Further investigation into the regulation of angiogenesis in the fetus and placenta may elucidate the causes of HLHS and associated growth abnormalities in some cases. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Aug 2015 · Placenta
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    ABSTRACT: Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach. We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 × 10-9), birth weight (p = 2.19 × 10-15), and gestational age (p = 1.51 × 10-7). Our parental-specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal height resulting in ~0.4 more gestational d. Limitations of this study include potential influences in causal inference by biological pleiotropy, assortative mating, and the nonrandom sampling of study subjects. Our results demonstrate that the observed association between maternal height and fetal growth measures (i.e., birth length and birth weight) is mainly defined by fetal genetics. In contrast, the association between maternal height and gestational age is more likely to be causal. In addition, our approach that utilizes the genetic score derived from the nontransmitted maternal haplotype as a genetic instrument is a novel extension to the Mendelian randomization methodology in casual inference between parental phenotype (or exposure) and outcomes in offspring.
    Full-text · Article · Aug 2015 · PLoS Medicine
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    ABSTRACT: Spontaneous preterm birth (SPTB) is a major factor associating with deaths and with lowered quality of life in humans. Environmental and genetic factors influence the susceptibility. Previously, by analyzing families with recurrent SPTB in linkage analysis, we identified a linkage peak close to the gene encoding CXCR3. Present objectives were to investigate the association of CXCR3 with SPTB in Finnish mothers (n = 443) and infants (n = 747), to analyze CXCR3 expression levels in human placenta and levels of its ligands in umbilical cord blood, and to verify the influence of Cxcr3 on SPTB-associating cytokines in mice. We detected an association between an intronic CXCR3 polymorphism, rs2280964, and SPTB in infants from families with recurrent preterm births (p = 0.009 versus term controls, odds ratio 0.52, 95% confidence interval 0.32-0.86). The minor allele was protective and undertransmitted to SPTB infants (p = 0.007). In the placenta and fetal membranes, the rs2280964 major allele homozygotes had higher expression levels than minor allele homozygotes; decidual trophoblasts showed strong CXCR3 immunoreactivity. Expression was higher in SPTB placentas compared with those from elective deliveries. Concentration of a CXCR3 ligand, CXCL9, was increased in cord blood from SPTB, and the protective rs2280964 allele was associated with low CXCL9. In CXCR3-deficient mice (Mus musculus), SPTB-associating cytokines were not acutely increased in amniotic fluid after preterm birth-inducing dose of maternal LPS. Our results indicate that CXCR3 contributes to SPTB. Activation of CXCR3 signaling may disturb the maternal-fetal tolerance, and this may promote labor. Copyright © 2015 by The American Association of Immunologists, Inc.
    Full-text · Article · Jul 2015 · The Journal of Immunology
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    Melinda G Arnett · Lisa M Muglia · Gloria Laryea · Louis J Muglia
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    ABSTRACT: The normal function of the hypothalamic-pituitary-adrenal (HPA) axis, and resultant glucocorticoid (GC) secretion, is essential for human health. Disruption of GC regulation is associated with both pathologic, psychological and physiological disease states such as depression, post-traumatic stress disorder, hypertension, diabetes, and osteopenia, amongst others. As such, understanding the mechanisms by which HPA output is tightly regulated in its responses to environmental stressors and circadian cues has been an active area of investigation for decades. Over the last 20 years, however, advances in gene targeting and genome modification in rodent models has allowed the detailed dissection of roles for key molecular mediators and brain regions responsible for this control in vivo to emerge. Here, we summarize work done to elucidate the function of critical neuropeptide systems, GC-signaling targets, and inflammation-associated pathways in HPA axis regulation and behavior, and highlight areas for future investigation.Neuropsychopharmacology accepted article preview online, 20 July 2015. doi:10.1038/npp.2015.215.
    Full-text · Article · Jul 2015 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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    Gloria Laryea · Melinda Arnett · Louis J Muglia
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    ABSTRACT: Glucocorticoid receptors (GR) in the paraventricular nucleus of the hypothalamus (PVN) are important regulators of negative feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Previous evaluation of endogenous PVN GR function in adult mice demonstrated that mice with loss of GR exon 3 in the PVN (Sim1Cre-GRe3Δ) have a hyperactive HPA axis, growth impairment and metabolic disruptions. Here, we hypothesized that lack of negative feedback inhibition of the HPA axis through PVN GR, as demonstrated through loss of PVN GR early in life, will have developmental-stage-specific consequences. Immunofluorescence revealed that Sim1Cre-GRe3Δ mice display PVN GR loss as early as post-natal day 2 compared to control mice. Sim1Cre-GRe3Δ mice compared to controls also displayed increased corticotropin-releasing hormone (CRH) mRNA in the PVN at post-natal day 10, as shown by in situ hybridization. Corticosterone radioimmunoassay revealed that the disruptions in PVN GR and CRH expression led to elevated basal corticosterone secretion in male Sim1Cre-GRe3Δ mice by early adolescence and increased stress-induced (restraint) corticosterone secretion in late adolescence into adulthood. In comparison, female Sim1Cre-GRe3Δ mice did not display corticosterone disruption until adulthood. Circadian rhythmicity of corticosterone secretion was normal for male and female mice at all age groups regardless of genotype with one exception. In late adolescence, female Sim1Cre-GRe3Δ mice had disrupted circadian corticosterone secretion due to significantly elevated circulating levels at nadir. We conclude that PVN GR function matures at an earlier developmental time point in male than in female mice and thus leads to later differential stress responsiveness between sexes.
    Full-text · Article · Jun 2015 · Stress (Amsterdam, Netherlands)
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    ABSTRACT: Corticosteroids act classically via cognate nuclear receptors to regulate gene transcription; however, increasing evidence supports rapid, non-transcriptional corticosteroid actions via activation of membrane receptors. Using whole-cell patch clamp recordings in hypothalamic slices from male mouse genetic models, we tested for non-genomic glucocorticoid actions at glutamate and GABA synapses in hypothalamic neuroendocrine cells, and for their dependence on the nuclear glucocorticoid receptor (GR). In enhanced green fluorescent protein (eGFP)-expressing corticotropin-releasing hormone (CRH) neurons of the paraventricular nucleus (PVN) and in magnocellular neurons of the PVN and supraoptic nucleus (SON), dexamethasone activated postsynaptic membrane-associated receptors and G protein signaling to elicit a rapid suppression of excitatory postsynaptic inputs, which was blocked by genetic deletion of CB1 receptors and a CB1 antagonist. In magnocellular neurons, dexamethasone also elicited a rapid nitric oxide-dependent increase in inhibitory postsynaptic inputs. These data indicate a rapid, synapse-specific glucocorticoid-induced retrograde endocannabinoid signaling at glutamate synapses and nitric oxide signaling at GABA synapses. Unexpectedly, the rapid glucocorticoid effects on both excitatory and inhibitory synaptic transmission were lost with conditional deletion of GR in the PVN and SON in slices from a Sim1-cre-directed conditional GR knockout mouse. Thus, the non-genomic glucocorticoid actions at glutamate and GABA synapses on PVN and SON neuroendocrine cells are dependent on the nuclear GR. The nuclear GR, therefore, is responsible for transducing the rapid steroid response at the membrane, or is either a critical component in the signaling cascade or regulates a critical component of the signaling cascade of a distinct membrane GR.
    Full-text · Article · Jun 2015 · Endocrinology
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    M G Arnett · M S Pan · W Doak · P E P Cyr · L M Muglia · L J Muglia
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    ABSTRACT: Early-life stress (ELS) leads to sustained changes in gene expression and behavior, increasing the likelihood of developing a psychiatric disorder in adulthood. The neurobiological basis for the later-in-life psychopathology is relatively unknown. The current study used a mouse model of ELS, achieved by daily maternal separations during the first 2 weeks of postnatal life, to test the role of amygdalar glucocorticoid receptor (GR) function in mediating the persistent increase in risk-taking behaviors. ELS produced a decrease in GR mRNA in the brain, with a notable reduction in the amygdala that was associated with sustained alterations in anxiety, fear and sociability-like behaviors. Lentiviral-mediated restoration of the GR mRNA deficit, specifically within the adult central nucleus of the amygdala (CeA), reversed the enduring changes in anxiety and social behavior after ELS. These results provide evidence of lasting changes in CeA GR neural circuitry following ELS and suggest a mechanistic role for GR-regulated processes in the CeA in mediating the lifelong maladaptive behaviors of ELS. We demonstrate that the long-lasting behavioral effects of ELS are reversible later in life and implicate the involvement of CeA GR-dependent activity in the sustained dysregulation of emotion following ELS.
    Full-text · Article · Apr 2015 · Translational Psychiatry
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    ABSTRACT: Objective: To test the hypothesis that exposure to fine particulate air pollution (PM2.5) is associated with stillbirth. Study design: Geo-spatial population-based cohort study using Ohio birth records (2006-2010) and local measures of PM2.5, recorded by the EPA (2005-2010) via 57 monitoring stations across Ohio. Geographic coordinates of the mother's residence for each birth were linked to the nearest PM2.5 monitoring station and monthly exposure averages calculated. The association between stillbirth and increased PM2.5 levels was estimated, with adjustment for maternal age, race, education level, quantity of prenatal care, smoking, and season of conception. Results: There were 349,188 live births and 1,848 stillbirths of non-anomalous singletons (20-42 weeks) with residence ≤10 km of a monitor station in Ohio during the study period. The mean PM2.5 level in Ohio was 13.3 μg/m3 [±1.8 SD, IQR(Q1: 12.1, Q3: 14.4, IQR: 2.3)], higher than the current EPA standard of 12 μg/m3. High average PM2.5 exposure through pregnancy was not associated with a significant increase in stillbirth risk, adjOR 1.21(95% CI 0.96,1.53), nor was it increased with high exposure in the 1st or 2nd trimester. However, exposure to high levels of PM2.5 in the third trimester of pregnancy was associated with 42% increased stillbirth risk, adjOR 1.42(1.06,1.91). Conclusions: Exposure to high levels of fine particulate air pollution in the third trimester of pregnancy is associated with increased stillbirth risk. Although the risk increase associated with high PM2.5 levels is modest, the potential impact on overall stillbirth rates could be robust as all pregnant women are potentially at risk.
    Full-text · Article · Mar 2015 · PLoS ONE
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    ABSTRACT: Transposable elements (TEs) comprise approximately half of the human genome, and several independent lines of investigation have demonstrated their role in rewiring gene expression during development, evolution, and oncogenesis. The identification of their regulatory effects has largely been idiosyncratic, by linking activity with isolated genes. Their distribution throughout the genome raises critical questions - do these elements contribute to broad tissue-and lineage-specific regulation? If so, in what manner, as enhancers, promoters, RNAs? Here, we devise a novel approach to systematically dissect the genome-wide consequences of TE insertion on gene expression, and test the hypothesis that classes of endogenous retrovirus long terminal repeats (LTRs) exert tissue-specific regulation of adjacent genes. Using correlation of expression patterns across 18 tissue types, we reveal the tissue-specific uncoupling of gene expression due to 62 different LTR classes. These patterns are specific to the retroviral insertion, as the same genes in species without the LTRs do not exhibit the same effect. While the LTRs can be transcribed themselves, the most highly transcribed TEs do not have the largest effects on adjacent regulation of coding genes, suggesting they function predominantly as enhancers. Moreover, the tissue-specific patterns of gene expression that are detected by our method arise from a limited number of genes, rather than as a general consequence of LTR integration. These findings identify basic principles of co-opting LTRs for genome evolution, and support the utility of our method for the analysis of TE, or other specific gene sets, in relation to the rest of the genome. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
    Full-text · Article · Mar 2015 · Genome Biology and Evolution
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    Kayleigh A Swaggart · Mihaela Pavlicev · Louis J Muglia
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    ABSTRACT: The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
    Full-text · Article · Feb 2015 · Cold Spring Harbor Perspectives in Medicine

  • No preview · Article · Jan 2015 · American Journal of Obstetrics and Gynecology

  • No preview · Article · Jan 2015 · American Journal of Obstetrics and Gynecology

Publication Stats

9k Citations
1,328.17 Total Impact Points

Institutions

  • 2012-2016
    • Cincinnati Children's Hospital Medical Center
      • • Department of Pediatrics
      • • Perinatal Institute
      Cincinnati, Ohio, United States
  • 2012-2015
    • University of Cincinnati
      • • Department of Pediatrics
      • • College of Medicine
      Cincinnati, Ohio, United States
  • 2013
    • University of Iowa
      • Department of Pediatrics
      Iowa City, Iowa, United States
  • 2010-2012
    • Vanderbilt University
      • Department of Pediatrics
      Нашвилл, Michigan, United States
  • 1999-2011
    • Washington University in St. Louis
      • • Department of Pediatrics
      • • Department of Obstetrics and Gynecology
      • • Department of Pathology and Immunology
      San Luis, Missouri, United States
  • 2007
    • Yale University
      • Department of Obstetrics, Gynecology and Reproductive Sciences
      New Haven, Connecticut, United States
    • Duke University
      Durham, North Carolina, United States
  • 2000
    • University of Missouri - St. Louis
      Saint Louis, Michigan, United States
  • 1995-2000
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1994-1999
    • Boston Children's Hospital
      • Division of Endocrinology
      Boston, Massachusetts, United States
  • 1997
    • Rady Children's Hospital
      San Diego, California, United States