Open AccessUnique transcriptomic landscapes identified in idiopathic spontaneous and infection related preterm births compared to normal term births
Author(s) -
Heather Brockway,
Suhas G. Kallapur,
Irina A. Buhimschi,
Catalin S. Buhimschi,
William E. Ackerman,
Louis J. Muglia,
Helen Jones
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0225062
Subject(s) - transcriptome , downregulation and upregulation , biology , placenta , gestational age , gestation , gene signature , gene expression profiling , pregnancy , fetus , andrology , immunology , bioinformatics , gene expression , medicine , gene , genetics
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.