The genetics of preterm birth: Progress and promise

Monangi, Nagendra; Brockway, Heather; House, Melissa; Zhang, Ge; Muglia, Louis J.

doi:10.1053/j.semperi.2015.09.005

Cited by 43 publications

(33 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The main etiological factors related to PTB are inflammation, hemorrhage, activation of maternal or fetal hypothalamic-pituitary axis, immune dysregulation, distension of the myometrium and cervical insufficiency [1,3,7,9]. All these process have diverse and distinctive ways of initiating labor but may share a common pathway that end in the release of mediators that stimulate myometrial contraction, degradation of extracellular matrix components, inflammation and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth

Pereyra

Bertoni

Sosa

et al. 2018

Preprint

View full text Add to dashboard Cite

15 16 Short title: Transcriptomic analysis of severe preterm birth 17 Key words: RNA-seq, preterm birth, gestational age, biomarkers 18 2 19Abstract 20 Preterm birth (PTB), defined as infant delivery before 37 weeks of completed gestation, results of 21 the interaction of both genetic and environmental components and constitutes a complex 22 multifactorial syndrome. Transcriptome analysis of PTB has proved challenging because of the 23 multiple causes of PTB and the numerous maternal and fetal gestational tissues that must interact 24 to facilitate parturition. A common pathway of labor and PTB may be the activation of fetal 25 membranes. In this work, chorioamnion membranes from severe preterm and term fetus were 26 analyzed using RNA sequencing. A total of 270 genes were differentially expressed (DE): 252 27 were up-regulated and 18 were down-regulated in the severe preterm compared to the term births. 28 We found great gene expression homogeneity in the control samples, and not in severe preterm 29 samples. In this work, we identified up-regulated pathways that were previously suggested as 30 leading to PTB like immunological and inflammatory paths. New pathways that were not 31 identified in preterm like the hemopoietic path appeared up-regulated in preterm membranes. A 32 group of 18 down-regulated genes discriminates between term and severe preterm cases. These 33 genes potentially characterize a severe preterm transcriptome pattern and therefore are candidate 34 genes for understanding the syndrome. Some of the down-regulated genes are involved in the 35 nervous system, morphogenesis (WNT-1, DLX5, PAPPA2) and ion channel complexes (KCNJ16, 36 KCNB1), making them good candidates as biomarkers of PTB.37 The identification of this DE gene pattern may help to develop a multi-gene disease classifier.38 These markers were generated in an admixtured South American population where PTB has a high 39 incidence. Since genetic background may impact differentially in different populations it is 40 mandatory to include populations like South American and African ones that are usually excluded 3 41 from high throughput approaches. These classifiers should be compared to those in other 42 populations to get a global landscape of PTB. 43 44 Introduction 45 Preterm birth (PTB), defined as the delivery of an infant before 37 weeks of completed gestation, 46 is a worldwide health problem and remains the leading cause of global perinatal morbidity and 47 mortality [1][2][3]. PTB is a complex, multifactorial syndrome comprised of multiple clinical 48 subtypes that can be defined as either 'spontaneous' or 'medically indicated' [4,5]. 70 % of PTB 49 cases are idiopathic; 5 % are due to the spontaneous onset of labor (sPTB) and the remaining 25 50 % are consequence of the preterm premature rupture of membranes (PPROM) [5,6]. PTB has also 51 been stratified according to gestational age (GA); neonates born between 24 and 33 weeks (severe 52 PTB) are at higher risk of death, and diseases later in life, than moderate PTB (GA betwee...

show abstract

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth

Pereyra

Bertoni

Sosa

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…This 25 has led to a lack of diagnostics and effective therapeutic interventions in the clinical setting. 26 the underlying molecular mechanisms of sPTB remain unclear [3]. Furthermore, the molecular differences 28 between infection and isPTB are not well understood.…”

Section: Introduction 17mentioning

confidence: 99%

“…Clinical characteristics of the placental villous samples included in the transcriptome analyses Data shown as median with range or total number with percent 1 ANOVA with Tukey's correction for multiple comparisons 2 Kruskal Wallis ANOVA with Dunn's correction for multiple comparisons3 Chi Square Analyses NS=Not significant *indicates the group significantly different from Term births.…”

mentioning

confidence: 99%

Unique transcriptomic landscapes identified in idiopathic spontaneous and infection related preterm births compared to normal term births

Brockway

Kallapur

Buhimschi

et al. 2018

Preprint

View full text Add to dashboard Cite

17Preterm birth (PTB) is leading contributor to infant death in the United States and globally, yet the 18 underlying mechanistic causes are not well understood. Previous studies have suggested a role for 19 advanced villous maturity in both spontaneous and iatrogenic preterm birth. To better understand 20 pathological and molecular basis of idiopathic spontaneous preterm birth (isPTB), we compared placental 21 morphology and transcriptomic analysis in carefully phenotyped cohorts of PTB due to intraamniotic 22 infection, isPTB, and healthy term placentae. Characteristic features of precocious placental villous 23 maturation were uniquely demonstrated in isPTB placentae. Transcriptomic analyses revealed isPTB 24 candidate genes. These include an upregulation of three IGF binding proteins (IGFBP1, IGFBP2, and 25All rights reserved. No reuse allowed without permission.was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx

show abstract

“…PTB and preeclampsia both have environmental risk factors as well as a genetic component that is not well understood. Family and pedigree studies of PTB and preeclampsia suggest strong genetic components, but heritability estimates for both vary considerably [5,6], and genetic associations found through genome-wide association studies (GWAS) of these and other disorders of pregnancy have been difficult to regulate [7,8]. Though a recent study of more than 43,000 women has identified and replicated several loci associated with gestational duration and preterm birth [9].…”

Section: Introductionmentioning

confidence: 99%

Genome-wide maps of distal gene regulatory regions active in the human placenta

Zhang

Simonti

Capra

2018

Preprint

View full text Add to dashboard Cite

Placental dysfunction is implicated in many pregnancy complications, including preeclampsia and preterm birth (PTB). While both these syndromes are influenced by environmental risk factors, they also have a substantial genetic component that is not well understood. Precisely controlled gene expression during development is crucial to proper placental function and often mediated through gene regulatory enhancers. However, we lack accurate maps of placental enhancer activity due to the challenges of assaying the placenta and the difficulty of comprehensively identifying enhancers. To address the gap in our knowledge of gene regulatory elements in the placenta, we used a two-step machine learning pipeline to synthesize existing functional genomics studies, transcription factor (TF) binding patterns, and evolutionary information to predict placental enhancers. The trained classifiers accurately distinguish enhancers from the genomic background and placental enhancers from enhancers active in other tissues. Genomic features collected from tissues and cell lines involved in pregnancy are the most predictive of placental regulatory activity. Applying the classifiers genome-wide enabled us to create a map of 33,010 predicted placental enhancers, including 4,562 high-confidence enhancer predictions. The genome-wide placental enhancers are significantly enriched nearby genes associated with placental development and birth disorders and for SNPs associated with gestational age. These genome-wide predicted placental enhancers provide candidate regions for further testing in vitro, will assist in guiding future studies of genetic associations with pregnancy phenotypes, and aid interpretation of potential mechanisms of action for variants found through genetic studies.

show abstract

The genetics of preterm birth: Progress and promise

Cited by 43 publications

References 77 publications

Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth

Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth

Unique transcriptomic landscapes identified in idiopathic spontaneous and infection related preterm births compared to normal term births

Genome-wide maps of distal gene regulatory regions active in the human placenta

Contact Info

Product

Resources

About