Abstract
Arginine Vasopressin Infusion In C57BL/6J Mice Induces Changes In The Placenta Transcriptome That Parallel Changes Observed In Placenta From Human Preeclampsia
The FASEB journal, Vol.32(S1), pp.911.4-911.4
04/2018
DOI: 10.1096/fasebj.2018.32.1_supplement.911.4
Abstract
Preeclampsia (PE), a cardiovascular disorder of late pregnancy characterized by new onset hypertension and proteinuria, remains a devastating disease affecting approximately 10% of all pregnancies in the United States. Multiple independent studies demonstrate a correlation between PE and elevated maternal plasma copeptin, the C‐terminal fragment of arginine vasopressin (AVP), which supports the concept that AVP secretion is elevated during PE. Previously we demonstrated the sufficiency of chronic low‐dose AVP infusion to initiate major phenotypes of PE in pregnant C57BL/6J mice, including hypertension, renal glomerular endotheliosis, intrauterine growth restriction, and altered placental morphology. Thus, we generally hypothesize that elevated AVP secretion is mechanistically involved in the pathogenesis of PE. Here, we tested the hypothesis that chronic infusion of AVP during gestation in mice would cause changes in the placental transcriptome which parallel changes documented in human PE. Placentas were collected on gestational day 12.5 from mice that received chronic saline or AVP (24 ng/hr) infusion through pregnancy and RNA‐sequencing was performed. Differential expression analyses revealed 87 transcripts, corresponding to 82 unique genes as well as 3 non‐coding RNAs, that were differentially expressed between AVP‐ and saline‐treated placentas (FDR < 0.1). Among the differentially expressed genes identified, six genes (Trpm2, Itih4, Ncmap, Sema3f, Scnn1g, Nfat5) had been previously associated with human PE. Ingenuity Pathway Analysis (IPA) identified that the disease and functional annotations significantly altered in AVP‐treated placentas included hypertension, preeclampsia, as well as cell death. As expected, IPA also identified likely canonical upstream mediators including AVP, desmopressin, and calcium signaling. Notably, Gene Set Enrichment Analysis (GSEA) and IPA did not uncover any enrichment for hypoxia‐associated signaling, suggesting that despite the PE‐like morphological and genetic signatures induced by AVP, AVP does not induce these phenotypes via placental hypoxia. Parallel in silico re‐analyses of a large published dataset from NCBI‐GEO (GSE75010) describing the transcriptomes of control and PE human placentas with various clinical covariates demonstrated that some subtypes of human PE similarly do not exhibit placental hypoxia. Collectively, these data highlight molecular phenotypes of PE induced within the placenta of mice by AVP, and highlight the potential utility of the AVP infusion approach to model specific subtypes of human PE.
This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.
Details
- Title: Subtitle
- Arginine Vasopressin Infusion In C57BL/6J Mice Induces Changes In The Placenta Transcriptome That Parallel Changes Observed In Placenta From Human Preeclampsia
- Creators
- Guorui Deng - University of IowaJeremy A. Sandgren - University of IowaHenry L. Keen - University of IowaKatherine J. Perschbacher - University of IowaShao Y. Zhang - University of IowaDonna A. Santillan - University of IowaGary L. Pierce - University of IowaKatherine N. Gibson‐Corley - University of IowaMark K. Santillan - University of IowaCurt D. Sigmund - University of IowaJustin L. Grobe - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.32(S1), pp.911.4-911.4
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.2018.32.1_supplement.911.4
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 04/2018
- Academic Unit
- Neuroscience and Pharmacology; Obstetrics and Gynecology; Health and Human Physiology; Iowa Institute of Human Genetics; Internal Medicine; Molecular Physiology and Biophysics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984267144102771
Metrics
3 Record Views