Temporal placental genome wide expression profiles reflect three phases of utero-placental blood flow during early to mid human gestation

James Breen, Dale McAninch, Tanja Jankovic-Karasoulos, Dylan McCullough, Melanie D Smith, Konstantinos Justinian Bogias, Qianhui Wan, Awais Choudhry, Nhi Hin, Stephen M Pederson, Tina Bianco-Miotto, Claire T Roberts

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Abstract

During early human placental development, extravillous cytotrophoblasts (EVT) invade the uterine vasculature to sequester a maternal blood supply. The impact of this on placental gene expression has not been established for normal pregnancy. Using RNA sequencing, we profiled placental chorionic villous tissues from 96 pregnancies at 6-23 weeks of gestation. We identified 1,048 genes that were differentially expressed between 6-10 weeks' and 11-23 weeks' of gestation. These are predominantly genes that are enriched in transcription factor signalling, inflammatory response and cell adhesion. Using a co-expression network and gene set enrichment analyses, we reveal three distinct phases of gene expression coincident with phases of maternal blood flow to the placenta that impact immune function and are likely driven by oxygen tension, potentially in a sex-specific manner. These data represent a comprehensive transcriptional profile of early placental development and point to significant environmental, genetic and regulatory triggers that drive gene expression.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis research was supported by a NIH grant awarded to CTR, TBM and JB (Maternal molecular profiles reflect placental function and development across gestation NIH oppRFA-HD-16-036 1 R01 HD089685-01). CTR is supported by an Australian National Health and Medical Research Council (NHMRC) Investigator Grant (GNT1174971) and a Matthew Flinders Fellowship from Flinders University. JB is supported by the James amp; Diana Ramsay Foundation. Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Women's and Children's Health Network Human Research Ethics Committee (REC2249/2/13), University of Adelaide Human Research Ethics Committee (H-137-2006), Queen Elizabeth Hospital and Lyell McEwin Hospital Human Research Ethics Committee (REC 1712/5/2008 and HREC/12/TQEHLMH/16).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesFull code and workflow available (https://github.com/jimmybgammyknee/earlyPlacentaRnaSeqProfile). All sequencing data is available for download at NCBI Gene Expression Omnibus (GEO) under Accession number: PRJNA633801.
Original languageUndefined/Unknown
JournalmedRxiv
DOIs
Publication statusPublished or Issued - 2020

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