Dataset Information

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

ABSTRACT: Preterm birth (PTB) is leading contributor to infant death in the United States and globally, yet the underlying mechanistic causes are not well understood. Histopathological studies of preterm birth suggest advanced villous maturity may have a role in idiopathic spontaneous preterm birth (isPTB). To better understand pathological and molecular basis of isPTB, we compared placental villous transcriptomes from carefully phenotyped cohorts of PTB due to infection or isPTB between 28-36 weeks gestation and healthy term placentas. Transcriptomic analyses revealed a unique expression signature for isPTB distinct from the age-matched controls that were delivered prematurely due to infection. This signature included the upregulation of three IGF binding proteins (IGFBP1, IGFBP2, and IGFBP6), supporting a role for aberrant IGF signaling in isPTB. However, within the isPTB expression signature, we detected secondary signature of inflammatory markers including TNC, C3, CFH, and C1R, which have been associated with placental maturity. In contrast, the expression signature of the gestational age-matched infected samples included upregulation of proliferative genes along with cell cycling and mitosis pathways. Together, these data suggest an isPTB molecular signature of placental hypermaturity, likely contributing to the premature activation of inflammatory pathways associated with birth and providing a molecular basis for idiopathic spontaneous birth.

SUBMITTER: Brockway HM

PROVIDER: S-EPMC6839872 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Brockway Heather M HM Kallapur Suhas G SG Buhimschi Irina A IA Buhimschi Catalin S CS Ackerman William E WE Muglia Louis J LJ Jones Helen N HN

PloS one 20191108 11

Preterm birth (PTB) is leading contributor to infant death in the United States and globally, yet the underlying mechanistic causes are not well understood. Histopathological studies of preterm birth suggest advanced villous maturity may have a role in idiopathic spontaneous preterm birth (isPTB). To better understand pathological and molecular basis of isPTB, we compared placental villous transcriptomes from carefully phenotyped cohorts of PTB due to infection or isPTB between 28-36 weeks gesta ...[more]

PMID: 31703110

Similar Datasets

Project description:IntroductionBlack African American (B/AA) women have a 2-fold to 3-fold elevated risk compared with non-Hispanic White (W) women for preterm birth. Further, preterm birth is the leading cause of mortality among B/AA infants, and among survivors, preterm infant adverse health outcomes occur disproportionately in B/AA infants. Racial inequities in maternal and infant health continue to pose a public health crisis despite the discovery >100 years ago. The purpose of this study was to expand on reported preterm infant outcome disparities. A life-course approach, accumulation of lifelong stress, including discrimination, may explain social factors causing preterm birth rate and outcome inequities in B/AA mothers.MethodsAnthropometric measures and clinical treatment information for 197 consented participants were milled from electronic health records across 4 years. The Neonatal Infant Stressor Scale was used to tally acute and chronic painful/stressful procedures. Neurobehavioral differences were investigated using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale.ResultsB/AA mothers gave birth to preterm infants earlier than W mothers. NICU hospitalization stays were extended more than 2 weeks for the significantly smaller B/AA preterm infants in comparison to the age-matched W preterm infants. A higher number of chronic lifesaving procedures with demonstrated altered stress response patterns were recorded for B/AA preterm infants.DiscussionThis cross-sectional analysis of preterm birth rates and preterm infant developmental and neurodevelopmental outcomes are presented in the context of NICU stress and pain, with attendant implications for infant mortality and future health disparities. Preterm birth rate and outcome inequities further support the need to develop interventions and policies that will reduce the impact of discrimination and improve social determinants of health for Black, Indigenous, and other People of Color.

Project description:During pregnancy, two fetomaternal interfaces, the placenta-decidua basalis and the fetal membrane-decidua parietals, allow for fetal growth and maturation and fetal-maternal crosstalk, and protect the fetus from infectious and inflammatory signaling that could lead to adverse pregnancy outcomes. While the placenta has been studied extensively, the fetal membranes have been understudied, even though they play critical roles in pregnancy maintenance and the initiation of term or preterm parturition. Fetal membrane dysfunction has been associated with spontaneous preterm birth (PTB, < 37 weeks gestation) and preterm prelabor rupture of the membranes (PPROM), which is a disease of the fetal membranes. However, it is unknown how the individual layers of the fetal membrane decidual interface (the amnion epithelium [AEC], the amnion mesenchyme [AMC], the chorion [CTC], and the decidua [DEC]) contribute to these pregnancy outcomes. In this study, we used a single-cell transcriptomics approach to unravel the transcriptomics network at spatial levels to discern the contributions of each layer of the fetal membranes and the adjoining maternal decidua during the following conditions: scheduled caesarian section (term not in labor [TNIL]; n = 4), vaginal term in labor (TIL; n = 3), preterm labor with and without rupture of membranes (PPROM; n = 3; and PTB; n = 3). The data included 18,815 genes from 13 patients (including TIL, PTB, PPROM, and TNIL) expressed across the four layers. After quality control, there were 11,921 genes and 44 samples. The data were processed by two pipelines: one by hierarchical clustering the combined cases and the other to evaluate heterogeneity within the cases. Our visual analytical approach revealed spatially recognized differentially expressed genes that aligned with four gene clusters. Cluster 1 genes were present predominantly in DECs and Cluster 3 centered around CTC genes in all labor phenotypes. Cluster 2 genes were predominantly found in AECs in PPROM and PTB, while Cluster 4 contained AMC and CTC genes identified in term labor cases. We identified the top 10 differentially expressed genes and their connected pathways (kinase activation, NF-κB, inflammation, cytoskeletal remodeling, and hormone regulation) per cluster in each tissue layer. An in-depth understanding of the involvement of each system and cell layer may help provide targeted and tailored interventions to reduce the risk of PTB.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets