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

Autoři: Heather M. Brockway aff001;  Suhas G. Kallapur aff002;  Irina A. Buhimschi aff003;  Catalin S. Buhimschi aff003;  William E. Ackerman aff003;  Louis J. Muglia aff001;  Helen N. Jones aff004
Působiště autorů: Center for Preterm Birth, Cincinnati Children’s Hospital Medical Center and Department of Pediatrics University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America aff001;  Divisions of Neonatology and Developmental Biology, David Geffen School of Medicine at the University of California, Los Angeles, California, United States of America aff002;  Department of Obstetrics and Gynecology, The University of Illinois College of Medicine, Chicago, Illinios, United States of America aff003;  Center for Fetal and Placental Research, Cincinnati Children’s Hospital Medical Center and Department of Surgery University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America aff004
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0225062


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.

Klíčová slova:

Placenta – Gene expression – Birth – Inflammation – Wnt signaling cascade – Transcriptome analysis – RNA sequencing – Preterm birth


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